Rheumatoid Arthritis

Current Care Guidelines
Working group set up by the Finnish Medical Society Duodecim and the Finnish Society for Rheumatology
9.3.2017

Current Care Guideline in Finnish «Nivelreuma»1

Please note that the guideline in Finnish, Nivelreuma «Nivelreuma»1, has been partially updated on Feb 18th, 2022. Therefore this English version is not currently up to date.

Summary

  • A patient suspected of having rheumatoid arthritis (RA) should be referred without delay to a multi-disciplinary rheumatology clinic for confirmation of the diagnosis and treatment start.
  • If left untreated or if treated with inferior drugs, patients with RA will experience disease progression and the RA will become a crippling disease. Effective treatment, on the other hand, can prevent disease progression for most patients.
  • The goal of treatment of early RA is prompt and sustained disease remission, which allows the patient to recover and maintain his or her functional capacity and working ability.
  • Treatment of active RA is started with combination pharmacotherapy: methotrexate, sulfasalazine, hydroxychloroquine and a low dose of glucocorticosteroid (usually prednisolone 5.0–7.5mg or an equivalent glucocorticosteroid in the morning for at least 6 months), if there are no contraindications. The efficacy of monotherapy is poorer than of combination therapy.
  • Methotrexate is the anchor drug, onto which other antirheumatic drugs are added. If methotrexate is contraindicated, leflunomide or azathioprine may be used.
  • A glucocorticosteroid should be injected intra-articularly into inflamed joints.
  • If active RA does not respond to combination treatment, the disease should be treated with biologics.
  • Since RA is associated with an increased risk of bone fractures, prevention of osteoporosis is important.
  • The patient's risk for cardiovascular disease should be assessed as a part of overall disease assessment.
  • Patient education aims to ensure the compliance of the patient with long-term treatment.
  • Patients are encouraged to exercise and to maintain their muscle strength.
  • The multi-disciplinary team at the rheumatology clinic follows the patient's condition and disease activity, and when the RA has been in stable remission for a given period of time, e.g., two years, it is recommended that the patient visits annually a physician with a good understanding of rheumatology. ̣

Goals

  • The aim of these guidelines is to improve and harmonise the diagnosis and management of RA to ensure that the quality of life, the working capacity and the functional capacity of patients with RA are maintained.

Target groups

  • These guidelines are targeted at health care professionals at all levels (e.g., general practice, occupational health service and specialised care), who care for patients with inflammatory rheumatic diseases.

Epidemiology

Incidence and prevalence

Aetiology

Mortality

Diagnostic goals

Importance of early diagnosis

Signs and symptoms

  • Joint inflammation is the sine qua non for a diagnosis of RA. Usually there is inflammation in several joints.
  • The inflamed joint is typically swollen, stiff in the morning and painful on movement, but not necessarily painful at rest.
  • Symptoms usually start in the small and medium-sized joints (MCP, PIP, wrists and MTP joints), although any joint may herald the disease.
  • In typical cases, joint inflammation is symmetrical.
  • Joint symptoms usually develop slowly and progress gradually, often in a relapsing-remitting pattern. RA may cause inflammation in the cervical spine, but symptoms of the lower back are not characteristic of RA.
    • The more active the joint inflammation is, the longer is the duration of morning stiffness.
    • Joint inspection and palpation are important. The inflamed joint is swollen and usually tender on palpation. Clinical examination of the joints requires experience.
    • Joint erosions usually develop first in the MTP joints «Eroosiot ilmaantuvat ensin jalkateriin.»A. One of the therapeutic goals is to have the patient on antirheumatic pharmacotherapy before joint erosions and permanent damage develop.
    • The erythrocyte sedimentation rate (ESR) and the concentraton of C-reactive protein (CRP) in the serum or plasma reflect disease activity acceptably well, but are not always increased. In long-standing chronic disease, ESR may be permanently high «Sokka T, Pincus T. Erythrocyte sedimentation rate,...»41.
  • Approximately two thirds of patients with early RA are RF- or anti-CCP-positive «Möttönen T, Paimela L, Leirisalo-Repo M ym. Only h...»42. These findings are highly suggestive for RA, but are not a requirement for the diagnosis.
    • If the patient has no joint inflammation, testing for RF and anti-CCP is usually not indicated.
    • Joint inflammation of unknown aetiology requires synovial fluid analysis, if possible. The synovial fluid is analysed for cell count and differential count of white blood cells and crystals. If the joint aspirate is turbid, bacterial staining and culture are in order. In RA, synovial fluid is usually somewhat cloudy due to a high leukocyte count and its viscosity is reduced.
    • If the leucocyte count of the synovial fluid is above 2,000 x 106/l, the finding is compatible with inflammation and suggests RA or some other form of arthritis (Table «Synovial fluid analysis: interpretation...»1).
Table 1. Synovial fluid analysis: interpretation
Interpretation Leucocyte count (x 106/l)
Non-inflammatory < 2 000
Inflammatory 2 000–60 000
Strongly inflammatory > 60 000

Main diagnostic criteria

  • There are several international criteria for the classification of RA, and the most recent one has been published by an American/European expert panel (ACR/EULAR2010; interactive table in Finnish «http://www.terveysportti.fi/xmedia/hoi/hoi21010/Nivelreuman_luokittelukriteerit.html»1). The criteria put special emphasis on the presentce of polyarthritis and of RF or anti-CCP present in high titres. Although the criteria are intended for disease classification, they aid clinical decision making.

Diagnostic levels

  • A patient suspected of having RA should be referred without delay to a unit specialised in rheumatology where the services of a multidisciplinary team are available to confirm the diagnosis and start treatment.
  • The note of referral should include information on the patient's history, signs, symptoms and clinical examination, and the numerical values of the ESR, CRP, RF and anti-CCP.
  • Oral glucocorticosteroids may mask symptoms and compromise the diagnosis. Non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular glucocorticosteroid injections may be used to alleviate the sympotoms of the patient «Luosujärvi Riitta. Niveltensisäinen kortisonihoito...»43.
  • If RA or some other chronic rheumatic joint diseases are not suspected and the diagnosis is, e.g., gout, reactive arthritis or erosive osteoarthritis, patients can often be treated outside rheumatology units.
  • Local health care arrangements may slightly differ from the current recommendations. See tables «Evaluation of patient with arthritis...»2 and «Special features to consider in differential diagnostics....»3.
Table 2. Evaluation of patient with arthritis
Clinical picture Evaluation
A All patients with arthritis
Laboratory tests
  • ESR, CRP, blood count, urine, urate in men and postmenopausal women
  • Synovial fluid analysis (cell counts, crystals, stain and culture if needed)
History (*see point D)
  • Duration of morning stiffness, tenderness in movements, pains and aches, low back pain in rest, previous trauma
  • History of joint symptoms, family history of arthritis
  • Psoriasis (skin, nails), preceeding diarrhea*, inflammatory symptoms in eyes*, symptoms in urination, pass from urethra*, sex contacts*
  • Other infections (e.g., tonsillitis)
  • Raynaud's phenomenon
  • Solar dermatitis, MTP1 arthritis after use of beer or diuretics (see point B)
B Monoarthritis (gout, pseudogout, bacterial arthritis, reactive arthritis)
  • Joint aspiration (cell counts, crystals, stain and culture if needed), urate (may be normal in acute gout)
C Chronic/primarily arthritis primarily of the small joints (rheumatoid arthritis?)
  • rheumatoid factor (RF) and anti-cyclic citrullinated peptide (aCCP) antibodies
D Patients who have history positive for (*)-marked items in point A and sudden arthritis in a young individual (infection related arthritis, reactive arthritis)
  • Stool culture, antibodies against Yersinia, Salmonella and Campylobacter
  • Chlamydia-PCR from urine (or antigen test from urethra or cervix), gonococcus culture, if needed
  • Chlamydia-antibodies (high titre may occur long after the primary infection and therefore urine-PCR is preferred for sensitivity and specificity)
E Possible tick bite or erythema migrans, EM (history / current)
  • Borrelia burgdorferi antibodies; Negative antibodies in early disease (EM or arthralgia) do not exclude Lyme borreliosis.
  • Consider repeating the test after 1–2 months
  • Arthritis: synovial fluid borrelia-PCR confirms but negative result does not rule out diagnosis
Skin eruptions (pox)
  • Consider rubella
  • Sindbis-antibodies if itching dermatitis late August-September
  • Consider Erythema infectiosum
F Fever and tonsillitis prior to arthritis (rheumatic fever?)
  • Streprococcus culture in pharynx
  • EKG
Heart murmur, migrating polyarthritis, long PQ in ECG, pericarditis (rheumatic fever?)
  • AST (when clinical suspicion of rheumatic fever; negative result indicates that rheumatic fever is unlikely)
  • Cardiac sonography
  • Chest radiograph
Table 3. Special features to consider in differential diagnostics.
Diagnosis Special features
Osteoarthritis Pain that is worse after activity or towards the end of the day
Bony growths (‘spurs') 'around joints' (e.g. fingers: DIP, PIP joints)
Limited range of movement or stiffness that abates
Spondyloarthropathy / Arthritis Runs in family HLA-B27-associated in 60–80% of patients Low extremities, Enthesitis
Usually oligo-monoarthritis
Dactylitis (see Aikakauskirja Duodecim «http://www.terveysportti.fi/xmedia/duo/duo95528.pdf»2 and figures «Daktyliitti»1, «Daktyliitti»2 (in Finnish))
Polymyalgia rheumatica Pain and stiffness in buttocks, hips, thighs, upper arms and shoulders
Patient may have synovitis in knees, wrists
Patient cannot squat or lift up arms
Stiffness after rest or long periods of inactivity
Consider possiblility of giant cell arteritis
Virus arthritis Sudden onset
Usually poly- or oligoarthritis
Usually dermatitis
Usually in the fall
Gout Sudden onset of arthritis, usually at night
Usually monoarthritis
Signs of inflammation: pain, swelling and redness
Most often MTP1 affected
Risk factors: metabolic syndrome, diuretics
Also elderly women with osteoarthritis might have gout
Septic arthritis Systemic symptoms usual
Sudden monoarthritis usual
Oligoarthritis rare but possible
Lyme borreliosis Erythema migrans, EM may be absent
May start with arthralgias and myalgias, later monoarthritis (usually knee) or oligoarthritis
Effusion more prominent than pain
Dactylitis or tendinitis possible
Psoriasis Family history
DIP joint involvement typical but rare
Usually oligoarthritis but polyarthritis and spondyloarthritis possible
Skin involvement
Nail involvement
Dactylitis, e.g., sausage toe or sausage finger
Picture 1.

Daktyliitti. © Markku Kauppi

Picture 2.

Daktyliitti. © Markku Kauppi

Imaging

  • Imaging supports clinical examination by identifying joint inflammation and permanent damage.

Radiography

  • Radiography should be performed in radiology units that provide high quality images by appropriate techniques «Laasonen L. Tavanomainen röntgentutkimus perifeeri...»44.
  • Radiographs are taken of the hands and feet as part of the diagnostic work-up of RA and other peripheral inflammatory joint diseases. A chest radiograph should be taken for differential diagnostic purposes and also before immunosuppressive pharmacotherapy is initiated.
  • Serial radiographs of the hand and feet may be taken judiciously over time to document disease follow-up.
  • RA does not affect the spine, except the cervical part. In patients with severe and long-lasting RA, spinal subluxation may occur, best identified on flexion/extension lateral radiographs. In severe rheumatic spinal disease, in particular if the patient has atlanto-axial subluxation (AAS), there is a risk of spinal cord damage of the cervical spine, if the neck is moved into extreme positions. This needs to be taken into account prior to general anaesthesia (flexion/extension radiographs of the cervical spine should be taken preoperatively). Cervical subluxations (e.g., AAS) are most reliably identified in lateral radiographs taken during flexion of the neck. These lateral images are the most important images of the rheumatoid cervical spine.

Sonography

MRI

  • Of all modern imaging techniques, MRI provides the best anatomical images of the joints and the periarticular soft tissue «Magneettikuvaus on paras kuvantamismenetelmä nivelreuman aiheuttamien muutosten toteamisessa.»A.
  • Contrast agents aid in the detection of active synovitis and enable earlier detection of erosions than conventional radiographs.
  • MRI is not usually needed for diagnostic or monitoring purposes. Unequivocal indications for MRI are differential diagnostic problems.
    • In severe disease of the cervical spine, MRI should be performed. Subluxations are identified by plain extension/flexion radiographs of the cervical spine. If displacement of the cervical vertebrae are seen, the effect of these anatomical changes are to be taken into account when the MRI images are interpreted to document any compression of the neural structures and spinal cord.

Treatment of RA

Early treatment of RA

Rehabilitation

  • Physical exercise as a form of rehabilitation has the strongest impact on the patient's functional capacity.
  • Rehabilitation, as well as pharmacotherapy, aims at enhancing the patient's functional capacity, working ability and overall wellbeing.
  • Pharmacotherapy and rehabilitation complement each other: the need for rehabilitation is often minimized, if active pharmacotherapy restores the patient's functional capacity.
  • WHO's ICF-classification (International Classification of Functioning, Disability and Health) «http://www.who.int/classifications/icf/en/»4 provides a framework for rehabilitation measures which may be applied to the patient herself or himself as well as to the physical or social environment of the patient.

Medical rehabilitation

Vocational rehabilitation

  • The goal of vocational rehabilitation is to support the employment of disabled subjects by developing their professional skills and working environment.
  • The patient's potential to retain his or her working capacity has to be assessed no later than after 90 weekdays of sickness allowance. This assessment is documented on a statement by the occupational health care physician. If the patient does not have the benefit of occupational health care services, the consultation of the employment office (TE-services) or the SII must be sought to assess the patient's possibilities for vocational rehabilitation. In addition, a multidisciplinary rehabilitation meeting arranged at a rheumatology or rehabilitation clinic may be helpful.
  • Referral to vocational rehabilitation requires a plan for rehabilitation, i.e., a statement made by the treating physician. For continuously employed patients, the pension insurance company takes on the responsibility for the rehabilitation costs, otherwise the SII is the payor.
  • Vocational rehabilitation is most beneficial when the subjects is threatened by disability or when work disability has been only temporary «Ammatillinen kuntoutus turvaa työkykyä todennäköisimmin silloin, kun kyseessä on työkyvyttömyyden uhka tai työkyvyttömyys on ollut tilapäistä.»B.

Ongoing rheumatoid arthritis treatment

  • There is no curative treatment for RA. Pharmacotherapy is usually continued for years or decades, because RA symptoms tend to relpse on discontinuation of treatment. For patients who have remained asymptomatic for years, medication can be decreased but close observation must be maintained.
  • 10–15% of patients with RA achieve sustained remission where no medication is needed «Nivelreumapotilaista 10–15 % voi päästä pitkäaikaiseen lääkkeettömään remissioon.»A.
  • The patient with RA should visit annually a physician who has a good understanding of treatment of RA.
  • If the medication has been reduced and the RA relapses, the pharmacotherapy to which the patient previously responded is re-introduced or dosages increased.
    • Subcutaneous or oral methotrexate may be re-introduced, even if it was discontinued after previous use, since discontinuation is often due to an ineffective dose or mild adverse events.
    • If there are no contraindications, the RACo-combination is introduced: methotrexate, sulfasalazine, hydroxychloroquine and a low-dose glucocorticosteroid (usually prednisolone 5.0–7.5mg daily or equivalent).
    • Leflunomide may be also used.
  • If the response to methotrexate-based combination treatment poor or absent, the RA is treated with biologics.
  • In long-lasting disease, triple combination therapy gives comparable results to treatment with biologics in patients who have responded inadequately to methotrexate monotherapy «Pidempäänkin kestäneessä nivelreumassa perinteinen yhdistelmähoito on biologisen lääkityksen veroinen potilailla, jotka eivät ole saaneet riittävää vastetta metotreksaatille.»A.

Pharmacotherapy of rheumatoid arthritis

Conventional synthetic disease modifying drugs (csDMARDs)

Table 4. Methotrexate (MTX), special aspects
Dose First dose 10–15mg sc or po
Second dose of MTX is the maintenance dose a week later «Bykerk VP, Akhavan P, Hazlewood GS ym. Canadian Rh...»115
Recommended maintenance dose in the beginning of treatment is 20–25mg once a week.
Later on, maintenance dose will be tailored for each individual, balanced between side effects and benefits.
Side effects Usual:
GI-tract, nausea, dizziness, hair loss, stomatitis, elevated liver enzymes, increased red cell volume
Rare:
Interstitial lung disease, cytopenias
Interactions Trimetoprim, probenecid
Contraindications Pregnancy and breast feeding
No need to interrupt MTX when planning fathering «Malm H. Isän kautta välittyvä teratogeneesi - aihe...»53
With caution Compromized kidney function (creatinine clearance < 60ml/min) «The effect of age and renal function on the effica...»52, liver diseases, lung fibrosis
Beneficial combination with Hydroxychloroquine + sulfasalazine, bDMARDs, cyclosporine
Other aspects "Anchor" drug
Bioavailability best sc or im vs po
Folic acid (5mg/week e.g. following day) improves tolerability and safety
If the serum aminotransferase increases to a level x 3 above the reference value, examinations are needed.
If no other reasons except MTX, establish highest dose that the patient tolerates.
Table 5. Sulfasalazine (SSZ), special aspects
Dose Begin 500mg × 2, after 1–2 weeks increase to 1 g × 2.
Side effects Usual:
GI-tract, mild CNS symptoms, oligospermia that resolves after discontinuation of SSZ, decreased sperm motility
Rare:
Severe skin reaction
Severe cytopenias
Interactions May decrease absorption of digoxin
Contraindications Hypersensitivity to sulfonamids and salicylates
Beneficial combination with Methotrexate + hydroxychloroquine Intramuscular gold (=natriumaurothiomalate)
Other aspects Part of triple combination
Can be used during pregnancy and breast feeding
Folic acid is recommended during pregnancy.
Table 6. Hydroxychloroquine (HCQ), special aspects
Dose About 5mg/kg/day
Side effects Usual:
GI-tract, mild CNS symptoms, nightmares, solar sensitivity Rare: Retinopathy, myopathy, kardiomyopathy
Interactions -
Contraindications Maculopathy of the eye
Beneficial combination with Intramuscular gold (=natriumaurothiomalate)
Methotrexate and sulfasalazine
Other aspects Part of triple combination
Can be used during pregnancy and breast feeding
A baseline examination by an ophthalmologist and after 5 years of use «Marmor MF, Kellner U, Lai TY ym. Revised recommend...»114
Table 7. Leflunomide, special aspects
Dose 20mg x 1/day (if issues of tolerability, 20mg every other day)
Side effects Diarrhea, reversible hair loss, dermatitis, headache
Interactions Rifampicin (increases concentration)
Contraindications Liver disease, pregnancy
Other aspects If aminotransferase levelös increase 2–3 times above normal, careful follow-up is indicated. If levels remain high, discontinue leflunomide and consider cholestyramine to wash out leflunomide.
Pay special attention to young women, as leflunomide may delay plans for pregnancy due to long withdrawal time of leflunomide
Table 8. Cyclosporine, special aspects
Dose Initial dose 2.5–3mg/kg/day, not >4mg/kg/day
Side effects Usual:
Increased hair growth, tremor, decreased kidney function, increased blood pressure, gingival overgrowth, GI-tract, paresthesia
Interactions Following drugs increase cyclosporin concentration:
Erythromycin, doxycycline, some antifungal drugs, calcium blockers, propaphenon, H2-blockers, metoclopramide, oral contraceptives and St. John’s wort (Hypericum perforatum)
Following drugs decrease cyclosporin concentration: Barbiturates, carbamazepine, phenytoin, metamizole, rifampicin, nafcillin, trimethoprim (i.v.), sulfoamides (i.v.)
Contraindications Malignancy, uncontrolled hypertension, compromized kidney function, immunodeficiency, pregnancy, breast feeding
Beneficial combination with Methotrexate
Other aspects If aminotransferase levelös increase 2–3 times above normal, careful follow-up is indicated. If levels remain high, discontinue leflunomide and consider cholestyramine to wash out leflunomide.
Pay special attention to young women, as leflunomide may delay plans for pregnancy due to long withdrawal time of leflunomide
Table 9. Intramuscular gold (natriumaurothiomalate), special aspects
Dose Intramuscular: after 10mg dose, 50mg weekly until a cumulative dose of 13mg/kg
Maintenance dose 50mg every 1–4 weeks
Side effects Usual:
Skin reactions, stomatitis, proteinuria
Rare:
Cytopenias, interstitial lung disease Polyneuropatia
Interactions
Contraindications Cytopenias, kidney or liver disease, pregnancy (3rd semester allowed)
Beneficial combination with Methotrexate
Hydroxychloroquine
Other aspects Proteinuria indicates membranous glomerulonefritis and treatment needs to be discontinued.
Table 10. Azathioprine, special aspects
Dose First week 50mg/day, thereafter 2–2.5mg/kg/day divided in 2–3 doses
Side effects Usual:
GI-tract, nausea, elevated aminotransferases
Rare:
Severe cytopenias
Interactions Allopurinol (life-threatening interaction)
Contraindications Pregnancy and breast feeding (relative contraindication)
Beneficial combination with
Other aspects Constantly elevated aminotransferases
Table 11. Azathioprine, special aspects
Dose 1–2 g/day, divided in two doses
Side effects Usual:
Nausea, diarrhea, stomach pain, infections, cytopenias
Rare:
Increased aminotransferases, decreased kidney function
Interactions Rifampicin, rifamycin
Contraindications Pregnancy and breast feeding
Beneficial combination with
Other aspects Live vaccines not recommended
Risk of skin cancer is increased
Table 12. Cyclophosphamide, special aspects
Dose 1.5–2.5mg/kg/day, divided in 2–3 doses, po
Side effects Usual:
GI-tract, cytopenias, infections, infertility
Rare:
Secondary malignancy
Interactions
Contraindications Susceptibility to infections, pregnancy, breast feeding
Beneficial combination with
Other aspects May be needed in systemic manifestations
Table 13. Pennicillamine, special aspects
Dose Initial dose 125mg × 1/day; increase by 125mg / 4 weeks until 500–600mg/day
Side effects Usual:
Skin reactions, stomatitis, taste disturbance, proteinuria
Rare:
Cytopenias, myasthenia gravis, polymyositis, SLE, Goodpasture's syndrome, pemphigus
Interactions
Contraindications Decreased kidney function
Pregnancy, breast feeding
Beneficial combination with -
Other aspects Needs special permit from Finnish Medicines Agency (Fimea)
Proteinuria indicates membranous glomerulonephritis and treatment needs to be discontinued.
Due to difficult dosage and side effects (especially dysgeusia) is rarely used nowadays

Biologic disease modifying drugs (bDMARDs)

Table 14. bDMARDs
Generic product Group Mode of action Half life Route of admin Dose Attention
Adalimumab TNF-α blocker Human monoclonal antibody 10–18 days sc 40mg every two weeks
Etanercept TNF-α blocker p75 receptor fusionprotein 3 days sc 50mg once a week or 25mg twice a week
Sertolitsumabpegol TNF-α blocker PEGylated Fab' fragment of a humanised TNF inhibitor monoclonal antibody 14 days sc 200mg every 2 weeks or 400mg once a month Starting dose to adults 400mg at weeks 0, 2, 4
Golimumab TNF-α blocker Human monoclonal antibody 9–15 days sc 50mg once a month If insufficient efficacy and patient's weight >100 kg, dose increase: 100mg once a month
Infliksimab TNF-α blocker Chimeric, monoclonal antibody 10 days iv 3mg/kg in weeks 0, 2, 6, thereafter every 8 weeks
Rituksimab B-cell inhibitor CD20 chimeric, monoclonal antibody 3–4 days iv 500–1 000mg 2 weeks apart, repeated after 6–12 months IgG levels at baseline and before every infusion

Infection and malignancy risk of biologics

TNF-α blockers

Interleukin 1 inhibitor (anakinra)

Interleukin 6 inhibitor (tocilizumab)

B-cell blocker (rituximab)

T-cell blocker (abatacept)

Glucocorticosteroids

Non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesics

Prevention of osteoporosis

  • The rheumatic inflammation and glucocorticosteroid treatment subject the patient to secondary osteoporosis. Glucocorticosteroids increase the risk of osteoporosis dose-dependently and the risk of fractures. Therefore, prevention of osteoporosis is important for patients on pharmacotherapy for RA (Current Care Guidelines of osteoporosis «Osteoporoosi»3 in Finnish).

Addressing the atherosclerosis risk

The impact of diet on rheumatoid symptoms

  • Special dietary interventions are not recommended for the treatment of RA. The effect of specific dietary regimens (vegetarian, Mediterranean, elemental, elimination diets) on the symptoms of RA (pain, stiffness, function) is uncertain «Hagen KB, Byfuglien MG, Falzon L ym. Dietary inter...»100. Studies have been small and their reliability affected by systematic errors of study designs.

Rheumatoid orthopaedic surgery

  • The goal of active anti-rheumatic medication is to obviate the need for operative treatment.
  • Statistics show that rheumaorthopaedic operations have declined notably during last 20 years due to more effective medication «Jämsen E, Virta LJ, Hakala M ym. The decline in jo...»102. Patients with chronic RA may have joint changes which may be relieved with orthopaedic surgery «Matti U.K. Lehto. Reumaortopedian valtakunnallinen...»103.
  • Synovectomy (today usually arthroscopic synovectomy) is indicated, if the inflammation in a single joint continues despite active anti-rheumatic pharmacotherapy. Synovectomy relieves often joint pain and stiffness. Postoperatively, effective anti-rheumatic pharmacotherapy should be continued to prevent re-synovitis. If the cartilage surface of the joint is in poor condition before synovectomy, the operative result may be poor or brief. A treatment option for "drug-therapy refractory synovitis" of the knee joint is radiosynovectomy, where a short-lived radionuclide is injected into the knee joint and removed after a while. This option is available only in some university hospitals in Finland.
  • Tenosynovitis and nodules in the tendons refractory to conservative therapy limit the movement of joints and may be treated surgically with tenosynovectomy. If tenosynovectomy is done to the flexor tendons of the wrist, the carpal canal is usually also opened and the median nerve liberated «Simmen BR, Bogoch ER, Goldhahn J. Surgery Insight:...»104.
  • Arthrodesis may relieve the pain of a severely destroyed joint and improve function of the whole extremity. Arthrodeses may correct severe deformities and prevent the progression of deformities. Usually, arthrodeses are performed in the wrist, subtalar joint, first metatarsophalangeal joint and sometimes in the finger joints.
  • Severe deformity in the cervical spine may be an indication for operative treatment. Severe anterior atlanto-axial subluxation (AAS) is usually treated surgically by fusing vertebrae C1 and C2.
  • The results of total hip and knee arthroplasties are good «Simmen BR, Bogoch ER, Goldhahn J. Surgery Insight:...»104. The prosthesis type for glenohumeral arthroplasty is selected individually. For patients with a severly degenerated rotator cuff, a reverse shoulder arthroplasty prosthesis is often used, because then the shoulder muscles may compensate for the loss of rotator cull function and generate satisfactory ranges of movement. The 10-year survival rate of prostheses of the large joints is 85–95% «Ikävalko M. Rheumatoid Elbow Destruction and its T...»105.
  • Prosthesis of the ankle, wrist and fingers may be used in selected RA cases.
  • Rheumaorthopaedic revision operations are often challenging «Simmen BR, Bogoch ER, Goldhahn J. Surgery Insight:...»104.
  • Painful rheumatoid nodules and bursae may require operative treatment.
  • The postoperative infection risk of patients with RA is elevated if the patient has certain concomitant diseases, like diabetes, impaired circulation in the operated limb and a history of infections after previous operations.
  • DMARDs, and especially biologics, often increase the risk of infections, which has to be taken into account when the surgical risks are evaluated. The biologics may be paused before and after an operation, depending on the patient and the DMARDs. The downside of discontinuing antirheumatic pharmacotherapy are, however, an increased risk of rheumatoid flare, an impaired surgical outcome and even an increased risk of infection. There is an abundant literature on how to discontinue antirheumatic pharmacotherapy before surgery, but strong evidence for the benefit of such a discontinuation is lacking. In general, it is reasonable to withhold biologics for 1–2 weeks before surgery and for the time after surgery until the surgical wound shows signs of good primary healing. Biologics need not be discontinued for minor, clean operations.

Patient education

  • Patient education improves compliance with drug treatment «Hill J, Bird H, Johnson S. Effect of patient educa...»106 and improves the patient's state of health, at least in the short term «Potilasohjaus vaikuttaa ainakin lyhyellä tähtäimellä edullisesti nivelreumapotilaiden terveydentilaan.»A.
    • The treatment of RA is based on a shared decisions between the patient and the treating physician. This presupposes that the patient knows the risks and benefits of the intended treatment «Smolen JS, Aletaha D, Bijlsma JW ym. Treating rheu...»107.
    • The role of the rheumatology nurse for efficient patient education is crucial.
  • The patient needs to understand:
    • the nature of RA and how it progresses, if untreated
    • how RA is treated
    • that remission is a realistic target in early disease and that stringent adherence by the patient to the prescribed medication is important
    • that the medication might have side effects and patients may need to switch medications, but the risks of having RA untreated are manyfold compared to the risks of the medication.
  • Smoking is a risk for RA.
  • Patient education needs to be comprehensive, well-structured and comprehensive. A supportive attitude of the treating physician and the rheumatology nurse is essential.
  • A physiotherapist should provide education on physical exercise.
  • As needed, the patient should be referred to an occupational therapist, podiatrist, dietician, psychotherapist or social worker.
  • The patient needs to have an assigned health care professional as a contact person.
  • Patient education may be provided following the motivational interview strategy «Lahti J, Maria R, Koski-Jännes A. Motivoiva haasta...»108. [HUOM! Motivoiva keskustelu; lisätäänkö linkki Oppiporttiin?]
  • Treatment pathway. [HUOM! Tässä kohtaa on suomenkielisessä suosituksessa linkki powerpoint-esitykseen]

Patient follow-up

  • We recommend that each rheumatology unit follows a clinical pathway for the care of patients with early RA. The objectives of following such a pathway are to guarantee that:
    • the patient starts the medication agreed on
    • possible adverse events are balanced against effective drug treatment
    • the treatment target is remission during the first few months of treatment
    • remission is sustained.
  • When the RA-patient attends for follow-up, disease activity is measured with the following scales:
  • The recommendation is to take radiographs of the hands and feet at baseline (at the time of diagnosis), at the two-year follow-up visit and thereafter as dictated by the patient's symptoms.
  • This working group recommends that the rheumatology unit ensures sustained remission for up to two years. Following this, the patient should have annual follow-up visits at a physician with a good understanding of rheumatology «Aktiivinen ote nivelreumapotilaan hoitoon parantaa merkitsevästi hoitotulosta.»A.
  • Blood tests for drug safety should be taken and assessed by a physician in primary care.
  • For use of medication during pregnancy and lactation see GRAVBASE-database «http://www.terveysportti.fi/terveysportti/dlv.koti?p_kielikoodi=fi&p_sovellustunnus=RI&p_mainos=E»11 (in Finnish, only for subscribers).
  • The risk of infection must be considered when biologics are used and appropriate vaccinations need to be guaranteed.
  • Close collaboration between the rheumatology unit and primary care is crucial since treatment of RA will go on for years and decades.
  • If the overall treatment is to be successful, relapses of RA must be recognised in primary care.
  • The patient is referred to a rheumatologist, if the relapse is not adequately controlled by the measures provided by the "toolbox" (see Table «GP's tool box...»15).
Table 15. GP's tool box
GP's tool box:
RA flares, what to do:
  • Mono/oligoarticular flare > intra-articular glucocorticosteroid injections
  • Dose increase of csDMARD
  • Low dose systemic glucocorticosteroid as a bridging therapy (5.0–7.5mg/day)
  • Confirm adequate response to therapy
  • If inadequate response, consultation of a rheumatologist
Increased symptoms without signs of RA activity:
  • Examine and treat underlying factors for pain
  • Optimize pain medications
  • Physiotherapy and other non-pharmacological therapies
  • Devices

Cost-effectiveness of the pharmacotherapy of RA

  • RA incurs high societal costs, including direct costs from increased health care resource use and indirect costs from reduced work productivity.
  • The early treatment outcome of RA is strongly predictive of direct and indirect costs «Puolakka K, Kautiainen H, Mottonen T ym. Use of th...»109, «Hallert E, Husberg M, Skogh T. 28-Joint count dise...»110. Early remission ensures maintained working capacity «Puolakka K, Kautiainen H, Möttönen T ym. Early sup...»49.
  • A good early treatment outcome, remission at best, prevents high costs and enhances the patient's quality of life.
  • If the activity of RA continues unabated, the patient is at risk of joint damage, loss of function and loss of working capacity. Work productivity costs have long since been the major part of the total costs «Kobelt G, Eberhardt K, Jönsson L ym. Economic cons...»111.
  • If conventional synthetic anti-rheumatic pharmacotherapy is not effective, even an expensive medication is cost-effective if it prevents disability and early work incapacitation and retirement.
  • Costs due to work incapacity are reduced also if pharmacotherapy is upgraded later during the disease process, if this allows the patient to regain his or her functional capacity to a level compatible with the requirements of the patient's assignments «Augustsson J, Neovius M, Cullinane-Carli C ym. Pat...»112.
  • Several studies have shown that the functional capacity of RA patients has, on average, improved in the past two decades. For those diagnosed with RA after the turn of millennium, the risk of work disability is smaller than for those diagnosed before than «Rantalaiho VM, Kautiainen H, Järvenpää S ym. Decli...»113.
  • There are several studies on the cost-effectiveness of different medications and combinations, but usually they have been comparisons between methotrexate monotherapy and other pharmacotherapeutic regimens in cases of methotrexate failure. They are not relevant for Finnish practice. Comparisons of various biologics have been based on short-term treatment studies, and the patient cohorts have not often been comparable.

Working group appointed by the Finnish Medical Society Duodecim and the Finnish Society for Rheumatology

Chair:

Kari Puolakka, MD, PhD, Adjunct professor, Specialist in Internal Medicine and Rheumatology, South Karelia Social and Health Care District (Eksote), Head of Department; Lappeenranta

Members:

Markku Hakala, MD, PhD, Adjunct professor, Specialist in Internal Medicine and Rheumatology; Tampere

Markku Kauppi, MD, PhD, Specialist in Internal Medicine and Rheumatology, Professor, Head of the rheumatology unitUniversity of Tampere and Päijät-Häme Central Hospital,Lahti, Finland.

Eero Mervaala, MD, PhD, Professor, University of Helsinki, Faculty of Medicine, Department of Pharmacology and FInnish Medical Society Duodecim (Current Care Editor)

Laura Pirilä, MD, PhD, Adjunct professor, Specialist in Internal Medicine, Geriatrics and Rheumatology; Head of Deparment of Rheumatology, Turku University Hospital, Division of Medicine, Hospital District of Southwest Finland

Tuulikki Sokka-Isler, MD, PhD, Professor, Specialist in Internal Medicine and Rheumatology, Head of Department; Central Finland Central Hospital and University of Eastern Finland

Klaus Suni, MD, Specialist in General Practise, health centre physician; Health Care Centre of the Jyväskylä Region

Consultant:

Raine Tiihonen, MD, PhD, Specialist in orthopedics and traumatology, Head of Department; Päijät-Häme Cental Hospital, Lahti, Finland

Disclosures

Markku Hakala: Grant (Pirkanmaa Hospital District), Consultanting fees (Finnish Rheumatism Association), membersip of a board or equal (Finnish Rheumatism Association), Speaking fees (MSD, Fysioline, GSK), License royalties (Duodecim)

Markku Kauppi: Consultanting fees (AbbVie, BMS, Berlin Chemie Menarin, MSD, Pfizer, Roche, UCB), Speaking fees (AbbVie, BMS, Berlin-Chemie Menarini, GSK, MSD, Pfizer, Roche, Sanofi, UCB), Reimbursement for attending meetings (BMS, Berlin-Chemie Meniarini, MSD, Pfizer, UCB)

Eero Mervaala: Consultanting fees (Kustannus Medicina Oy), Employment (Yhtyneet Medix Laboratoriot), Speaking fees (Pharmaceutical Information Centre Ltd)

Laura Pirilä: Consultanting fees (Pfizer Oy), Speaking fees (AbbVie oy, Bristol-Myers Squibb (Finland), GlaxoSmithKline OY, Labquality Days/Labquality oy, Pfizer Oy, Pohjois-Savon sairaahoitopiiri, Roche oy, the Scandinavian Neuropathological Society, the Finnish Society for Rheumatolgy, University of Turku, Turunmaan Duodecim ry, UCB Pharma Oy Finland), Reimbursement for attending meetings (Actellion Pharmaceuticals Finland, Bristol Myer Squibb Finland, Roche Oy, UCB Pharma Oy Finland)

Kari Puolakka: Grant (Pfizer), Consultanting fees (Abbvie, Bristol-Myers Squibb, MSD, Pfizer, Roche, UCB), Speaking fees (Bristol-Myers Squibb, Pfizer, UCB), Reimbursement for attending meetings (Bristol-Myers Squibb, Pfizer, Roche)

Tuulikki Sokka-Isler: Grant (Abbvie, Hospira, Pfizer), Consultanting fees (Hospira, Novartis, Orion, Pfizer, UCB), Speaking fees (Abbvie, BMS, Hospira, MSD, Medac, Pfizer, Roche, UCB)

Klaus Suni: Reimbursement for attending meetings (MSD, Pfizer)

Translation

Elena Nikiphorou MBBS/BSc, MRCP, PGCME, MD (Res), FHEA

Tuulikki Sokka-Isler

Laura Pirilä

Markku Hakala

Kari Puolakka

Language revision:

MediDocs Ltd, Robert Paul

Limitation of responsibility

The clinical practice guidelines of the Finnish Medical Society Duodecim are summaries on the diagnostics and effectiveness of therapy on single diseases and are produced by experts. They do not replace the judgement of a physician or other healthcare specialist on the best possible diagnostics and therapy of an individual patient.

References

  1. Deane KD. Preclinical rheumatoid arthritis (autoantibodies): an updated review. Curr Rheumatol Rep 2014;16:419 «PMID: 24643396»PubMed
  2. Nielsen SF, Bojesen SE, Schnohr P ym. Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a prospective cohort study. BMJ 2012;345:e5244 «PMID: 22956589»PubMed
  3. Hazes JM, Luime JJ. The epidemiology of early inflammatory arthritis. Nat Rev Rheumatol 2011;7:381-90 «PMID: 21670767»PubMed
  4. Wevers-de Boer KV, Heimans L, Huizinga TW ym. Drug therapy in undifferentiated arthritis: a systematic literature review. Ann Rheum Dis 2013;72:1436-44 «PMID: 23744979»PubMed
  5. Rantalaiho, Pirilä, Kautiainen Puolakka. Miten tuoretta nivelreumaa hoidetaan Suomessa. Suom Lääkäril 2013;44:2833-38
  6. Smolen JS, Landewé R, Breedveld FC ym. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014;73:492-509 «PMID: 24161836»PubMed
  7. Aletaha D, Neogi T, Silman AJ ym. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-81 «PMID: 20872595»PubMed
  8. Rossini M, Rossi E, Bernardi D ym. Prevalence and incidence of rheumatoid arthritis in Italy. Rheumatol Int 2014;34:659-64 «PMID: 24610538»PubMed
  9. Humphreys JH, Verstappen SM, Hyrich KL ym. The incidence of rheumatoid arthritis in the UK: comparisons using the 2010 ACR/EULAR classification criteria and the 1987 ACR classification criteria. Results from the Norfolk Arthritis Register. Ann Rheum Dis 2013;72:1315-20 «PMID: 22945499»PubMed
  10. Englund M, Jöud A, Geborek P ym. Prevalence and incidence of rheumatoid arthritis in southern Sweden 2008 and their relation to prescribed biologics. Rheumatology (Oxford) 2010;49:1563-9 «PMID: 20444855»PubMed
  11. Puolakka K, Kautiainen H, Pohjolainen T ym. Rheumatoid arthritis (RA) remains a threat to work productivity: a nationwide register-based incidence study from Finland. Scand J Rheumatol 2010;39:436-8 «PMID: 20513211»PubMed
  12. Aho K, Kaipiainen-Seppänen O, Heliövaara M ym. Epidemiology of rheumatoid arthritis in Finland. Semin Arthritis Rheum 1998;27:325-34 «PMID: 9572714»PubMed
  13. Pedersen JK, Svendsen AJ, Hørslev-Petersen K. Prevalence of rheumatoid arthritis in the southern part of denmark. Open Rheumatol J 2011;5:91-7 «PMID: 22216071»PubMed
  14. Neovius M, Simard JF, Askling J ym. Nationwide prevalence of rheumatoid arthritis and penetration of disease-modifying drugs in Sweden. Ann Rheum Dis 2011;70:624-9 «PMID: 21149495»PubMed
  15. Biver E, Beague V, Verloop D ym. Low and stable prevalence of rheumatoid arthritis in northern France. Joint Bone Spine 2009;76:497-500 «PMID: 19767228»PubMed
  16. Widdifield J, Paterson JM, Bernatsky S ym. The rising burden of rheumatoid arthritis surpasses rheumatology supply in Ontario. Can J Public Health 2013;104:e450-5 «PMID: 24495819»PubMed
  17. Gabriel SE, Michaud K. Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther 2009;11:229 «PMID: 19519924»PubMed
  18. Cross M, Smith E, Hoy D ym. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73:1316-22 «PMID: 24550173»PubMed
  19. Wallenius M, Skomsvoll JF, Irgens LM ym. Postpartum onset of rheumatoid arthritis and other chronic arthritides: results from a patient register linked to a medical birth registry. Ann Rheum Dis 2010;69:332-6 «PMID: 19717397»PubMed
  20. Kurkó J, Besenyei T, Laki J ym. Genetics of rheumatoid arthritis - a comprehensive review. Clin Rev Allergy Immunol 2013;45:170-9 «PMID: 23288628»PubMed
  21. Aho K, Koskenvuo M, Tuominen J ym. Occurrence of rheumatoid arthritis in a nationwide series of twins. J Rheumatol 1986;13:899-902 «PMID: 3820198»PubMed
  22. Silman AJ, MacGregor AJ, Thomson W ym. Twin concordance rates for rheumatoid arthritis: results from a nationwide study. Br J Rheumatol 1993;32:903-7 «PMID: 8402000»PubMed
  23. Hensvold AH, Magnusson PK, Joshua V ym. Environmental and genetic factors in the development of anticitrullinated protein antibodies (ACPAs) and ACPA-positive rheumatoid arthritis: an epidemiological investigation in twins. Ann Rheum Dis 2015;74:375-80 «PMID: 24276366»PubMed
  24. Klareskog L, Stolt P, Lundberg K ym. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 2006;54:38-46 «PMID: 16385494»PubMed
  25. Padyukov L, Silva C, Stolt P ym. A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum 2004;50:3085-92 «PMID: 15476204»PubMed
  26. Huizinga TW, Amos CI, van der Helm-van Mil AH ym. Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum 2005;52:3433-8 «PMID: 16255021»PubMed
  27. Myllykangas-Luosujärvi R. Mortality and causes of death in rheumatoid arthritis in Finland in 1989. Väitöskirja. Acta Universitatis Tamperensis. Ser A vol 461, 1995
  28. Sihvonen S, Korpela M, Laippala P ym. Death rates and causes of death in patients with rheumatoid arthritis: a population-based study. Scand J Rheumatol 2004;33:221-7 «PMID: 15370716»PubMed
  29. Dadoun S, Zeboulon-Ktorza N, Combescure C ym. Mortality in rheumatoid arthritis over the last fifty years: systematic review and meta-analysis. Joint Bone Spine 2013;80:29-33 «PMID: 22459416»PubMed
  30. Ogdie A, Haynes K, Troxel AB ym. Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis: a longitudinal cohort study. Ann Rheum Dis 2014;73:149-53 «PMID: 23264338»PubMed
  31. Kuller LH, Mackey RH, Walitt BT ym. Determinants of mortality among postmenopausal women in the women's health initiative who report rheumatoid arthritis. Arthritis Rheumatol 2014;66:497-507 «PMID: 24574208»PubMed
  32. Listing J, Kekow J, Manger B ym. Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFa inhibitors and rituximab. Ann Rheum Dis 2015;74:415-21 «PMID: 24291654»PubMed
  33. Wasko MC, Dasgupta A, Hubert H ym. Propensity-adjusted association of methotrexate with overall survival in rheumatoid arthritis. Arthritis Rheum 2013;65:334-42 «PMID: 23044791»PubMed
  34. van Tuyl LH, Boers M, Lems WF ym. Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis. Ann Rheum Dis 2010;69:807-12 «PMID: 19451137»PubMed
  35. Nakajima A, Saito K, Kojima T ym. No increased mortality in patients with rheumatoid arthritis treated with biologics: results from the biologics register of six rheumatology institutes in Japan. Mod Rheumatol 2013;23:945-52 «PMID: 23073692»PubMed
  36. Simard JF, Neovius M, Askling J ym. Mortality rates in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: drug-specific comparisons in the Swedish Biologics Register. Arthritis Rheum 2012;64:3502-10 «PMID: 22886739»PubMed
  37. Humphreys JH, Warner A, Chipping J ym. Mortality trends in patients with early rheumatoid arthritis over 20 years: results from the Norfolk Arthritis Register. Arthritis Care Res (Hoboken) 2014;66:1296-301 «PMID: 24497371»PubMed
  38. Masuda H, Miyazaki T, Shimada K ym. Disease duration and severity impacts on long-term cardiovascular events in Japanese patients with rheumatoid arthritis. J Cardiol 2014;64:366-70 «PMID: 24685688»PubMed
  39. Puolakka K, Kautiainen H, Pohjolainen T ym. No increased mortality in incident cases of rheumatoid arthritis during the new millennium. Ann Rheum Dis 2010;69:2057-8 «PMID: 20448281»PubMed
  40. Kerola AM, Nieminen TVM, Virta LJ, Kautiainen H, Kerola T, Pohjolainen T, Kauppi MJ, Puolakka K: No Increased Cardiovascular Mortality among Early Rheumatoid Arthritis Patients - a Nationwide Register Study in 2000 - 2008. Clin Exp Rheumatol 2015, painossa.
  41. Sokka T, Pincus T. Erythrocyte sedimentation rate, C-reactive protein, or rheumatoid factor are normal at presentation in 35%-45% of patients with rheumatoid arthritis seen between 1980 and 2004: analyses from Finland and the United States. J Rheumatol 2009;36:1387-90 «PMID: 19411389»PubMed
  42. Möttönen T, Paimela L, Leirisalo-Repo M ym. Only high disease activity and positive rheumatoid factor indicate poor prognosis in patients with early rheumatoid arthritis treated with "sawtooth" strategy. Ann Rheum Dis 1998;57:533-9 «PMID: 9849312»PubMed
  43. Luosujärvi Riitta. Niveltensisäinen kortisonihoito. SLL 2015;70:1165-1170
  44. Laasonen L. Tavanomainen röntgentutkimus perifeeristen artriittien diagnostiikassa. Suom Lääkäril 1992;47:487
  45. van der Heijde DM. Joint erosions and patients with early rheumatoid arthritis. Br J Rheumatol 1995;34 Suppl 2:74-8 «PMID: 8535653»PubMed
  46. Graudal NA, Jurik AG, de Carvalho A ym. Radiographic progression in rheumatoid arthritis: a long-term prospective study of 109 patients. Arthritis Rheum 1998;41:1470-80 «PMID: 9704647»PubMed
  47. Sokka T. Näkökulma. T2T-manifesti tähtää nivelreuman parempaan hoitoon. Suom Lääkäril 2011;18:1472-3
  48. Rantalaiho V, Puolakka K, Korpela M ym. Long-term results of the FIN-RACo trial; treatment with a combination of traditional disease-modifying anti-rheumatic drugs is an excellent option in early rheumatoid arthritis. Clin Exp Rheumatol 2012;30:S27-31 «PMID: 23073350»PubMed
  49. Puolakka K, Kautiainen H, Möttönen T ym. Early suppression of disease activity is essential for maintenance of work capacity in patients with recent-onset rheumatoid arthritis: five-year experience from the FIN-RACo trial. Arthritis Rheum 2005;52:36-41 «PMID: 15641055»PubMed
  50. Möttönen T, Hannonen P, Leirisalo-Repo M ym. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 1999;353:1568-73 «PMID: 10334255»PubMed
  51. Bingham SJ, Buch MH, Lindsay S ym. Parenteral methotrexate should be given before biological therapy. Rheumatology (Oxford) 2003;42:1009-10 «PMID: 12869673»PubMed
  52. The effect of age and renal function on the efficacy and toxicity of methotrexate in rheumatoid arthritis. Rheumatoid Arthritis Clinical Trial Archive Group. J Rheumatol 1995;22:218-23 «PMID: 7738941»PubMed
  53. Malm H. Isän kautta välittyvä teratogeneesi - aiheetonta pelkoa syytä välttää. Suom Lääkäril 2009;11:1036-7
  54. Vliet Vlieland TP, van den Ende CH. Nonpharmacological treatment of rheumatoid arthritis. Curr Opin Rheumatol 2011;23:259-64 «PMID: 21346575»PubMed
  55. van den Hout WB, Tijhuis GJ, Hazes JM ym. Cost effectiveness and cost utility analysis of multidisciplinary care in patients with rheumatoid arthritis: a randomised comparison of clinical nurse specialist care, inpatient team care, and day patient team care. Ann Rheum Dis 2003;62:308-15 «PMID: 12634227»PubMed
  56. Puolakka K, Kautiainen H, Möttönen T ym. Cost of Finnish statutory inpatient rehabilitation and its impact on functional and work capacity of patients with early rheumatoid arthritis: experience from the FIN-RACo trial. Scand J Rheumatol 2007;36:270-7 «PMID: 17763204»PubMed
  57. Gabay C, Hasler P, Kyburz D ym. Biological agents in monotherapy for the treatment of rheumatoid arthritis. Swiss Med Wkly 2014;144:w13950 «PMID: 24723273»PubMed
  58. Sokka T, Kautiainen H, Pincus T ym. Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database. Ann Rheum Dis 2009;68:1666-72 «PMID: 19643759»PubMed
  59. Putrik P, Ramiro S, Kvien TK ym. Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis 2014;73:198-206 «PMID: 23467636»PubMed
  60. Putrik P, Ramiro S, Kvien TK ym. Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth? Ann Rheum Dis 2014;73:2010-21 «PMID: 23940213»PubMed
  61. Sokka T, Haugeberg G, Asikainen J ym. Similar clinical outcomes in rheumatoid arthritis with more versus less expensive treatment strategies. Observational data from two rheumatology clinics. Clin Exp Rheumatol 2013;31:409-14 «PMID: 23415074»PubMed
  62. Kauppi M, Pukkala E, Isomäki H. Elevated incidence of hematologic malignancies in patients with Sjögren's syndrome compared with patients with rheumatoid arthritis (Finland). Cancer Causes Control 1997;8:201-4 «PMID: 9134244»PubMed
  63. Isomäki HA, Hakulinen T, Joutsenlahti U. Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J Chronic Dis 1978;31:691-6 «PMID: 730824»PubMed
  64. Le Blay P, Mouterde G, Barnetche T ym. Risk of malignancy including non-melanoma skin cancers with anti-tumor necrosis factor therapy in patients with rheumatoid arthritis: meta-analysis of registries and systematic review of long-term extension studies. Clin Exp Rheumatol 2012;30:756-64 «PMID: 22766000»PubMed
  65. Smolen JS, Aletaha D, Koeller M ym. New therapies for treatment of rheumatoid arthritis. Lancet 2007;370:1861-74 «PMID: 17570481»PubMed
  66. Isomäki P. Biologisten lääkkeiden vasta-aineet reumataudeissa - teho katoaa? Suom Lääkär 2014;34:2013
  67. Garcês S, Antunes M, Benito-Garcia E ym. A preliminary algorithm introducing immunogenicity assessment in the management of patients with RA receiving tumour necrosis factor inhibitor therapies. Ann Rheum Dis 2014;73:1138-43 «PMID: 23666932»PubMed
  68. Garcês S, Demengeot J, Benito-Garcia E. The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis. Ann Rheum Dis 2013;72:1947-55 «PMID: 23223420»PubMed
  69. Bendtzen K, Geborek P, Svenson M ym. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum 2006;54:3782-9 «PMID: 17133559»PubMed
  70. Ducourau E, Mulleman D, Paintaud G ym. Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases. Arthritis Res Ther 2011;13:R105 «PMID: 21708018»PubMed
  71. Keane J, Gershon S, Wise RP ym. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001;345:1098-104 «PMID: 11596589»PubMed
  72. Mikuls TR, Moreland LW. Benefit-risk assessment of infliximab in the treatment of rheumatoid arthritis. Drug Saf 2003;26:23-32 «PMID: 12495361»PubMed
  73. Alldred A. Etanercept in rheumatoid arthritis. Expert Opin Pharmacother 2001;2:1137-48 «PMID: 11583065»PubMed
  74. Konttinen Y, Nordström D, Honkanen V ym. Biologisten reumalääkkeiden käyttöön liittyvät riskit. Lääkärilehti 2004:43:4129-36
  75. Navarro-Millán I, Singh JA, Curtis JR. Systematic review of tocilizumab for rheumatoid arthritis: a new biologic agent targeting the interleukin-6 receptor. Clin Ther 2012;34:788-802.e3 «PMID: 22444783»PubMed
  76. Bari SF, Khan A, Lawson T. C reactive protein may not be reliable as a marker of severe bacterial infection in patients receiving tocilizumab. BMJ Case Rep 2013;2013: «PMID: 24177456»PubMed
  77. Edwards JC, Szczepanski L, Szechinski J ym. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;350:2572-81 «PMID: 15201414»PubMed
  78. Cohen SB, Emery P, Greenwald MW ym. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006;54:2793-806 «PMID: 16947627»PubMed
  79. Scher JU. B-cell therapies for rheumatoid arthritis. Bull NYU Hosp Jt Dis 2012;70:200-3 «PMID: 23259629»PubMed
  80. van Vollenhoven RF, Emery P, Bingham CO 3rd ym. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol 2010;37:558-67 «PMID: 20110520»PubMed
  81. Kaine J, Gladstein G, Strusberg I ym. Evaluation of abatacept administered subcutaneously in adults with active rheumatoid arthritis: impact of withdrawal and reintroduction on immunogenicity, efficacy and safety (phase Iiib ALLOW study). Ann Rheum Dis 2012;71:38-44 «PMID: 21917824»PubMed
  82. Lopes RV, Furtado RN, Parmigiani L ym. Accuracy of intra-articular injections in peripheral joints performed blindly in patients with rheumatoid arthritis. Rheumatology (Oxford) 2008;47:1792-4 «PMID: 18820311»PubMed
  83. Sibbitt WL Jr, Peisajovich A, Michael AA ym. Does sonographic needle guidance affect the clinical outcome of intraarticular injections? J Rheumatol 2009;36:1892-902 «PMID: 19648304»PubMed
  84. Konai MS, Vilar Furtado RN, Dos Santos MF ym. Monoarticular corticosteroid injection versus systemic administration in the treatment of rheumatoid arthritis patients: a randomized double-blind controlled study. Clin Exp Rheumatol 2009;27:214-21 «PMID: 19473560»PubMed
  85. Weitoft T, Forsberg C. Importance of immobilization after intraarticular glucocorticoid treatment for elbow synovitis: a randomized controlled study. Arthritis Care Res (Hoboken) 2010;62:735-7 «PMID: 20461791»PubMed
  86. Wallen M, Gillies D. Intra-articular steroids and splints/rest for children with juvenile idiopathic arthritis and adults with rheumatoid arthritis. Cochrane Database Syst Rev 2006;:CD002824 «PMID: 16437446»PubMed
  87. Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J ym. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013;382:769-79 «PMID: 23726390»PubMed
  88. Radner H, Ramiro S, van der Heijde DM ym. How do gastrointestinal or liver comorbidities influence the choice of pain treatment in inflammatory arthritis? A Cochrane systematic review. J Rheumatol Suppl 2012;90:74-80 «PMID: 22942333»PubMed
  89. Brooks J, Warburton R, Beales IL. Prevention of upper gastrointestinal haemorrhage: current controversies and clinical guidance. Ther Adv Chronic Dis 2013;4:206-22 «PMID: 23997925»PubMed
  90. Marks JL, van der Heijde DM, Colebatch AN ym. Pain pharmacotherapy in patients with inflammatory arthritis and concurrent cardiovascular or renal disease: a Cochrane systematic review. J Rheumatol Suppl 2012;90:81-4 «PMID: 22942334»PubMed
  91. Doherty M, Hawkey C, Goulder M ym. A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain. Ann Rheum Dis 2011;70:1534-41 «PMID: 21804100»PubMed
  92. Whittle SL, Richards BL, van der Heijde DM ym. The efficacy and safety of opioids in inflammatory arthritis: a Cochrane systematic review. J Rheumatol Suppl 2012;90:40-6 «PMID: 22942328»PubMed
  93. Ramiro S, Radner H, van der Heijde DM ym. Combination therapy for pain management in inflammatory arthritis: a Cochrane systematic review. J Rheumatol Suppl 2012;90:47-55 «PMID: 22942329»PubMed
  94. Solomon DH, Karlson EW, Rimm EB ym. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 2003;107:1303-7 «PMID: 12628952»PubMed
  95. Chung CP, Oeser A, Raggi P ym. Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum 2005;52:3045-53 «PMID: 16200609»PubMed
  96. Bergholm R, Leirisalo-Repo M, Vehkavaara S ym. Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis. Arterioscler Thromb Vasc Biol 2002;22:1637-41 «PMID: 12377742»PubMed
  97. Park YB, Lee SK, Lee WK ym. Lipid profiles in untreated patients with rheumatoid arthritis. J Rheumatol 1999;26:1701-4 «PMID: 10451065»PubMed
  98. Aviña-Zubieta JA, Choi HK, Sadatsafavi M ym. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008;59:1690-7 «PMID: 19035419»PubMed
  99. Tam LS, Gladman DD, Hallett DC ym. Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus. J Rheumatol 2000;27:2142-5 «PMID: 10990225»PubMed
  100. Hagen KB, Byfuglien MG, Falzon L ym. Dietary interventions for rheumatoid arthritis. Cochrane Database Syst Rev 2009;:CD006400 «PMID: 19160281»PubMed
  101. Koivuniemi R ja Leirisalo-Repo M.Tulehduksellisiin reumasairauksiin liittyy suurentunut sydän- ja verisuinisairauksien riski. S Lääkäril 2015; 70:711-5
  102. Jämsen E, Virta LJ, Hakala M ym. The decline in joint replacement surgery in rheumatoid arthritis is associated with a concomitant increase in the intensity of anti-rheumatic therapy: a nationwide register-based study from 1995 through 2010. Acta Orthop 2013;84:331-7 «PMID: 23992137»PubMed
  103. Matti U.K. Lehto. Reumaortopedian valtakunnallinen toteuttaminen. Selvitysmiehen raportti.67s. Sosiaali- ja terveysministeriön raportteja ja muistioita 2012:3. «http://urn.fi/URN:ISBN:958-952-00-3206-7»12
  104. Simmen BR, Bogoch ER, Goldhahn J. Surgery Insight: orthopedic treatment options in rheumatoid arthritis. Nat Clin Pract Rheumatol 2008;4:266-73 «PMID: 18334981»PubMed
  105. Ikävalko M. Rheumatoid Elbow Destruction and its Treatment with Souter-Strathclyde Arthroplasty. Acta Universitatis Tamperensis; 1014, Tampereen yliopisto, Tampere 2004. 
  106. Hill J, Bird H, Johnson S. Effect of patient education on adherence to drug treatment for rheumatoid arthritis: a randomised controlled trial. Ann Rheum Dis 2001;60:869-75 «PMID: 11502614»PubMed
  107. Smolen JS, Aletaha D, Bijlsma JW ym. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010;69:631-7 «PMID: 20215140»PubMed
  108. Lahti J, Maria R, Koski-Jännes A. Motivoiva haastattelu kaksoisdiagnoosipotilaiden hoidossa. Duodecim 2013;129:2063-9 «http://www.duodecimlehti.fi/web/guest/etusivu/artikkeli?tunnus=duo11266»13
  109. Puolakka K, Kautiainen H, Mottonen T ym. Use of the Stanford Health Assessment Questionnaire in estimation of long-term productivity costs in patients with recent-onset rheumatoid arthritis. Scand J Rheumatol 2009;38:96-103 «PMID: 19274516»PubMed
  110. Hallert E, Husberg M, Skogh T. 28-Joint count disease activity score at 3 months after diagnosis of early rheumatoid arthritis is strongly associated with direct and indirect costs over the following 4 years: the Swedish TIRA project. Rheumatology (Oxford) 2011;50:1259-67 «PMID: 21292734»PubMed
  111. Kobelt G, Eberhardt K, Jönsson L ym. Economic consequences of the progression of rheumatoid arthritis in Sweden. Arthritis Rheum 1999;42:347-56 «PMID: 10025930»PubMed
  112. Augustsson J, Neovius M, Cullinane-Carli C ym. Patients with rheumatoid arthritis treated with tumour necrosis factor antagonists increase their participation in the workforce: potential for significant long-term indirect cost gains (data from a population-based registry). Ann Rheum Dis 2010;69:126-31 «PMID: 19470527»PubMed
  113. Rantalaiho VM, Kautiainen H, Järvenpää S ym. Decline in work disability caused by early rheumatoid arthritis: results from a nationwide Finnish register, 2000-8. Ann Rheum Dis 2013;72:672-7 «PMID: 22679306»PubMed
  114. Marmor MF, Kellner U, Lai TY ym. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology 2011;118:415-22 «PMID: 21292109»PubMed
  115. Bykerk VP, Akhavan P, Hazlewood GS ym. Canadian Rheumatology Association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol 2012;39:1559-82 «PMID: 21921096»PubMed
  116. Ajeganova S, Svensson B, Hafström I ym. Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial. BMJ Open 2014;4:e004259 «PMID: 24710131»PubMed
  117. Alasaarela E, Takalo R, Tervonen O ym. Sonography and MRI in the evaluation of painful arthritic shoulder. Br J Rheumatol 1997;36:996-1000 «PMID: 9376998»PubMed
  118. Aletaha D, Funovits J, Breedveld FC ym. Rheumatoid arthritis joint progression in sustained remission is determined by disease activity levels preceding the period of radiographic assessment. Arthritis Rheum 2009;60:1242-9 «PMID: 19404938»PubMed
  119. Allaire SH, Li W, LaValley MP. Reduction of job loss in persons with rheumatic diseases receiving vocational rehabilitation: a randomized controlled trial. Arthritis Rheum 2003;48:3212-8 «PMID: 14613285»PubMed
  120. Anderson JJ, Wells G, Verhoeven AC ym. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 2000;43:22-9 «PMID: 10643696»PubMed
  121. Arvidsson S, Bergman S, Arvidsson B ym. Effects of a self-care promoting problem-based learning programme in people with rheumatic diseases: a randomized controlled study. J Adv Nurs 2013;69:1500-14 «PMID: 22973890»PubMed
  122. Aviña-Zubieta JA, Abrahamowicz M, De Vera MA ym. Immediate and past cumulative effects of oral glucocorticoids on the risk of acute myocardial infarction in rheumatoid arthritis: a population-based study. Rheumatology (Oxford) 2013;52:68-75 «PMID: 23192907»PubMed
  123. Bae SC, Gun SC, Mok CC ym. Improved health outcomes with etanercept versus usual DMARD therapy in an Asian population with established rheumatoid arthritis. BMC Musculoskelet Disord 2013;14:13 «PMID: 23294908»PubMed
  124. Benbouazza K, Benchekroun B, Rkain H ym. Profile and course of early rheumatoid arthritis in Morocco: a two-year follow-up study. BMC Musculoskelet Disord 2011;12:266 «PMID: 22111841»PubMed
  125. Bijlsma JW. Disease control with glucocorticoid therapy in rheumatoid arthritis. Rheumatology (Oxford) 2012;51 Suppl 4:iv9-13 «PMID: 22685274»PubMed
  126. Bilberg A, Ahlmén M, Mannerkorpi K. Moderately intensive exercise in a temperate pool for patients with rheumatoid arthritis: a randomized controlled study. Rheumatology (Oxford) 2005;44:502-8 «PMID: 15728422»PubMed
  127. Boers M, Verhoeven AC, Markusse HM ym. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997;350:309-18 «PMID: 9251634»PubMed
  128. Boers M. Drugs and cardiovascular risk in inflammatory arthritis: another case of glucocorticoid-bashing? Ann Rheum Dis 2015;74:e33 «PMID: 25714930»PubMed
  129. Braun J, Kästner P, Flaxenberg P ym. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum 2008;58:73-81 «PMID: 18163521»PubMed
  130. Brosseau L, Judd MG, Marchand S ym. Transcutaneous electrical nerve stimulation (TENS) for the treatment of rheumatoid arthritis in the hand. Cochrane Database Syst Rev 2003;:CD004377 «PMID: 12918009»PubMed
  131. Brosseau L, Robinson V, Wells G ym. Low level laser therapy (Classes I, II and III) for treating rheumatoid arthritis. Cochrane Database Syst Rev 2005;:CD002049 «PMID: 16235295»PubMed
  132. Buckland-Wright JC, Clarke GS, Chikanza IC ym. Quantitative microfocal radiography detects changes in erosion area in patients with early rheumatoid arthritis treated with myocrisine. J Rheumatol 1993;20:243-7 «PMID: 8474059»PubMed
  133. Burmester GR, Rubbert-Roth A, Cantagrel A ym. A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe rheumatoid arthritis (SUMMACTA study). Ann Rheum Dis 2014;73:69-74 «PMID: 23904473»PubMed
  134. Buttgereit F, Doering G, Schaeffler A ym. Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial. Lancet 2008;371:205-14 «PMID: 18207016»PubMed
  135. Buttgereit F, Doering G, Schaeffler A ym. Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis. Ann Rheum Dis 2010;69:1275-80 «PMID: 20542963»PubMed
  136. Buttgereit F, Mehta D, Kirwan J ym. Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2). Ann Rheum Dis 2013;72:204-10 «PMID: 22562974»PubMed
  137. Campbell L, Chen C, Bhagat SS ym. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology (Oxford) 2011;50:552-62 «PMID: 21078627»PubMed
  138. Casimiro L, Brosseau L, Robinson V ym. Therapeutic ultrasound for the treatment of rheumatoid arthritis. Cochrane Database Syst Rev 2002;:CD003787 «PMID: 12137714»PubMed
  139. Chalmers AC, Busby C, Goyert J ym. Metatarsalgia and rheumatoid arthritis--a randomized, single blind, sequential trial comparing 2 types of foot orthoses and supportive shoes. J Rheumatol 2000;27:1643-7 «PMID: 10914845»PubMed
  140. Chatzidionysiou K, Lie E, Nasonov E ym. Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: pooled data from 10 European registries. Ann Rheum Dis 2011;70:1575-80 «PMID: 21571731»PubMed
  141. Cho NS, Hwang JH, Chang HJ ym. Randomized controlled trial for clinical effects of varying types of insoles combined with specialized shoes in patients with rheumatoid arthritis of the foot. Clin Rehabil 2009;23:512-21 «PMID: 19403553»PubMed
  142. Choy EH, Smith CM, Farewell V ym. Factorial randomised controlled trial of glucocorticoids and combination disease modifying drugs in early rheumatoid arthritis. Ann Rheum Dis 2008;67:656-63 «PMID: 17768173»PubMed
  143. Conrad KJ, Budiman-Mak E, Roach KE ym. Impacts of foot orthoses on pain and disability in rheumatoid arthritics. J Clin Epidemiol 1996;49:1-7 «PMID: 8598501»PubMed
  144. Cutolo M, Iaccarino L, Doria A ym. Efficacy of the switch to modified-release prednisone in rheumatoid arthritis patients treated with standard glucocorticoids. Clin Exp Rheumatol 2013;31:498-505 «PMID: 23415134»PubMed
  145. de Buck PD, le Cessie S, van den Hout WB ym. Randomized comparison of a multidisciplinary job-retention vocational rehabilitation program with usual outpatient care in patients with chronic arthritis at risk for job loss. Arthritis Rheum 2005;53:682-90 «PMID: 16208658»PubMed
  146. de Jong PH, Hazes JM, Barendregt PJ ym. Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. Ann Rheum Dis 2013;72:72-8 «PMID: 22679301»PubMed
  147. del Rincón I, Battafarano DF, Restrepo JF ym. Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis. Arthritis Rheumatol 2014;66:264-72 «PMID: 24504798»PubMed
  148. Dellhag B, Wollersjö I, Bjelle A. Effect of active hand exercise and wax bath treatment in rheumatoid arthritis patients. Arthritis Care Res 1992;5:87-92 «PMID: 1390969»PubMed
  149. den Uyl D, van Raalte DH, Nurmohamed MT ym. Metabolic effects of high-dose prednisolone treatment in early rheumatoid arthritis: balance between diabetogenic effects and inflammation reduction. Arthritis Rheum 2012;64:639-46 «PMID: 21953589»PubMed
  150. Egsmose C, Lund B, Borg G ym. Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year followup of a prospective double blind placebo controlled study. J Rheumatol 1995;22:2208-13 «PMID: 8835550»PubMed
  151. Engvall IL, Brismar K, Hafström I ym. Treatment with low-dose prednisolone is associated with altered body composition but no difference in bone mineral density in rheumatoid arthritis patients: a controlled cross-sectional study. Scand J Rheumatol 2011;40:161-8 «PMID: 21077801»PubMed
  152. Engvall IL, Svensson B, Tengstrand B ym. Impact of low-dose prednisolone on bone synthesis and resorption in early rheumatoid arthritis: experiences from a two-year randomized study. Arthritis Res Ther 2008;10:R128 «PMID: 18986531»PubMed
  153. Feldman DE, Bernatsky S, Houde M ym. Early consultation with a rheumatologist for RA: does it reduce subsequent use of orthopaedic surgery? Rheumatology (Oxford) 2013;52:452-9 «PMID: 22949726»PubMed
  154. Gaujoux-Viala C, Nam J, Ramiro S ym. Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2014;73:510-5 «PMID: 24395555»PubMed
  155. Genovese MC, Covarrubias A, Leon G ym. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheum 2011;63:2854-64 «PMID: 21618201»PubMed
  156. Ghazi M, Kolta S, Briot K ym. Prevalence of vertebral fractures in patients with rheumatoid arthritis: revisiting the role of glucocorticoids. Osteoporos Int 2012;23:581-7 «PMID: 21350894»PubMed
  157. Giraudet-Le Quintrec JS, Mayoux-Benhamou A, Ravaud P ym. Effect of a collective educational program for patients with rheumatoid arthritis: a prospective 12-month randomized controlled trial. J Rheumatol 2007;34:1684-91 «PMID: 17610321»PubMed
  158. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF ym. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 2005;52:3381-90 «PMID: 16258899»PubMed
  159. Gorter SL, Bijlsma JW, Cutolo M ym. Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2010;69:1010-4 «PMID: 20448288»PubMed
  160. Graudal N, Jürgens G. Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons. Arthritis Rheum 2010;62:2852-63 «PMID: 20560138»PubMed
  161. Gremese E, Salaffi F, Bosello SL ym. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study. Ann Rheum Dis 2013;72:858-62 «PMID: 22798566»PubMed
  162. Grigor C, Capell H, Stirling A ym. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 2004;364:263-9 «PMID: 15262104»PubMed
  163. Grønning K, Rannestad T, Skomsvoll JF ym. Long-term effects of a nurse-led group and individual patient education programme for patients with chronic inflammatory polyarthritis - a randomised controlled trial. J Clin Nurs 2014;23:1005-17 «PMID: 23875718»PubMed
  164. Grønning K, Skomsvoll JF, Rannestad T ym. The effect of an educational programme consisting of group and individual arthritis education for patients with polyarthritis--a randomised controlled trial. Patient Educ Couns 2012;88:113-20 «PMID: 22277625»PubMed
  165. Hafström I, Albertsson K, Boonen A ym. Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study. Ann Rheum Dis 2009;68:508-13 «PMID: 18420939»PubMed
  166. Hall J, Skevington SM, Maddison PJ ym. A randomized and controlled trial of hydrotherapy in rheumatoid arthritis. Arthritis Care Res 1996;9:206-15 «PMID: 8971230»PubMed
  167. Hall J, Swinkels A, Briddon J ym. Does aquatic exercise relieve pain in adults with neurologic or musculoskeletal disease? A systematic review and meta-analysis of randomized controlled trials. Arch Phys Med Rehabil 2008;89:873-83 «PMID: 18452734»PubMed
  168. Hammond A, Freeman K. The long-term outcomes from a randomized controlled trial of an educational-behavioural joint protection programme for people with rheumatoid arthritis. Clin Rehabil 2004;18:520-8 «PMID: 15293486»PubMed
  169. Harris JA, Bykerk VP, Hitchon CA ym. Determining best practices in early rheumatoid arthritis by comparing differences in treatment at sites in the Canadian Early Arthritis Cohort. J Rheumatol 2013;40:1823-30 «PMID: 24037554»PubMed
  170. Harrison BJ, Symmons DP, Brennan P ym. Natural remission in inflammatory polyarthritis: issues of definition and prediction. Br J Rheumatol 1996;35:1096-100 «PMID: 8948295»PubMed
  171. Haugeberg G, Morton S, Emery P ym. Effect of intra-articular corticosteroid injections and inflammation on periarticular and generalised bone loss in early rheumatoid arthritis. Ann Rheum Dis 2011;70:184-7 «PMID: 20805297»PubMed
  172. Hawke F, Burns J, Radford JA ym. Custom-made foot orthoses for the treatment of foot pain. Cochrane Database Syst Rev 2008;:CD006801 «PMID: 18646168»PubMed
  173. Hetland ML, Hørslev-Petersen K. The CIMESTRA study: intra-articular glucocorticosteroids and synthetic DMARDs in a treat-to-target strategy in early rheumatoid arhtritis. Clin Exp Rheumatol 2012;30:S44-9 «PMID: 23079125»PubMed
  174. Hetland ML, Stengaard-Pedersen K, Junker P ym. Aggressive combination therapy with intra-articular glucocorticoid injections and conventional disease-modifying anti-rheumatic drugs in early rheumatoid arthritis: second-year clinical and radiographic results from the CIMESTRA study. Ann Rheum Dis 2008;67:815-22 «PMID: 17878209»PubMed
  175. Hetland ML, Stengaard-Pedersen K, Junker P ym. Combination treatment with methotrexate, cyclosporine, and intraarticular betamethasone compared with methotrexate and intraarticular betamethasone in early active rheumatoid arthritis: an investigator-initiated, multicenter, randomized, double-blind, parallel-group, placebo-controlled study. Arthritis Rheum 2006;54:1401-9 «PMID: 16645967»PubMed
  176. Hetland ML, Østergaard M, Ejbjerg B ym. Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis: impact of joint area, repeated injections, MRI findings, anti-CCP, IgM-RF and CRP. Ann Rheum Dis 2012;71:851-6 «PMID: 22302316»PubMed
  177. Hirvonen HE, Mikkelsson MK, Kautiainen H ym. Effectiveness of different cryotherapies on pain and disease activity in active rheumatoid arthritis. A randomised single blinded controlled trial. Clin Exp Rheumatol 2006;24:295-301 «PMID: 16870097»PubMed
  178. Hoekstra M, Haagsma C, Neef C ym. Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis. J Rheumatol 2004;31:645-8 «PMID: 15088287»PubMed
  179. Hoes JN, van der Goes MC, van Raalte DH ym. Glucose tolerance, insulin sensitivity and ß-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids. Ann Rheum Dis 2011;70:1887-94 «PMID: 21908880»PubMed
  180. Houssien DA, Scott DL. Early referral and outcome in rheumatoid arthritis. Scand J Rheumatol 1998;27:300-2 «PMID: 9751472»PubMed
  181. Hurkmans E, van der Giesen FJ, Vliet Vlieland TP ym. Dynamic exercise programs (aerobic capacity and/or muscle strength training) in patients with rheumatoid arthritis. Cochrane Database Syst Rev 2009;:CD006853 «PMID: 19821388»PubMed
  182. Hørslev-Petersen K, Hetland ML, Junker P ym. Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebo-controlled trial. Ann Rheum Dis 2014;73:654-61 «PMID: 23434570»PubMed
  183. Isaacs JD, Cohen SB, Emery P ym. Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis. Ann Rheum Dis 2013;72:329-36 «PMID: 22689315»PubMed
  184. Jansen LM, van Schaardenburg D, van Der Horst-Bruinsma IE ym. Predictors of functional status in patients with early rheumatoid arthritis. Ann Rheum Dis 2000;59:223-6 «PMID: 10700432»PubMed
  185. John H, Hale ED, Treharne GJ ym. A randomized controlled trial of a cognitive behavioural patient education intervention vs a traditional information leaflet to address the cardiovascular aspects of rheumatoid disease. Rheumatology (Oxford) 2013;52:81-90 «PMID: 22942402»PubMed
  186. Kellner H, Bornholdt K, Hein G. Leflunomide in the treatment of patients with early rheumatoid arthritis--results of a prospective non-interventional study. Clin Rheumatol 2010;29:913-20 «PMID: 20496042»PubMed
  187. Kirwan JR, Hewlett S, Cockshott Z ym. Clinical and psychological outcomes of patient education in rheumatoid arthritis. Musculoskeletal Care 2005;3:1-16 «PMID: 17041989»PubMed
  188. Klarenbeek NB, van der Kooij SM, Güler-Yüksel M ym. Discontinuing treatment in patients with rheumatoid arthritis in sustained clinical remission: exploratory analyses from the BeSt study. Ann Rheum Dis 2011;70:315-9 «PMID: 21068104»PubMed
  189. Kourbeti IS, Ziakas PD, Mylonakis E. Biologic therapies in rheumatoid arthritis and the risk of opportunistic infections: a meta-analysis. Clin Infect Dis 2014;58:1649-57 «PMID: 24647016»PubMed
  190. Laiho K, Soini I, Kautiainen H ym. Can we rely on magnetic resonance imaging when evaluating unstable atlantoaxial subluxation? Ann Rheum Dis 2003;62:254-6 «PMID: 12594114»PubMed
  191. Lard LR, Visser H, Speyer I ym. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 2001;111:446-51 «PMID: 11690569»PubMed
  192. Launois R, Avouac B, Berenbaum F ym. Comparison of certolizumab pegol with other anticytokine agents for treatment of rheumatoid arthritis: a multiple-treatment Bayesian metaanalysis. J Rheumatol 2011;38:835-45 «PMID: 21239748»PubMed
  193. LE Blay P, Mouterde G, Barnetche T ym. Short-term risk of total malignancy and nonmelanoma skin cancers with certolizumab and golimumab in patients with rheumatoid arthritis: metaanalysis of randomized controlled trials. J Rheumatol 2012;39:712-5 «PMID: 22382344»PubMed
  194. Leirisalo-Repo M, Kautiainen H, Laasonen L ym. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann Rheum Dis 2013;72:851-7 «PMID: 22753402»PubMed
  195. Ljung L, Askling J, Rantapää-Dahlqvist S ym. The risk of acute coronary syndrome in rheumatoid arthritis in relation to tumour necrosis factor inhibitors and the risk in the general population: a national cohort study. Arthritis Res Ther 2014;16:R127 «PMID: 24941916»PubMed
  196. Lopez-Olivo MA, Tayar JH, Martinez-Lopez JA ym. Risk of malignancies in patients with rheumatoid arthritis treated with biologic therapy: a meta-analysis. JAMA 2012;308:898-908 «PMID: 22948700»PubMed
  197. Luukkainen R, Isomäki H, Kajander A. Effect of gold treatment on the progression of erosions in RA patients. Scand J Rheumatol 1977;6:123-7 «PMID: 897587»PubMed
  198. Machado DA, Guzman RM, Xavier RM ym. Open-label observation of addition of etanercept versus a conventional disease-modifying antirheumatic drug in subjects with active rheumatoid arthritis despite methotrexate therapy in the Latin American region. J Clin Rheumatol 2014;20:25-33 «PMID: 24356474»PubMed
  199. Mathieux R, Marotte H, Battistini L ym. Early occupational therapy programme increases hand grip strength at 3 months: results from a randomised, blind, controlled study in early rheumatoid arthritis. Ann Rheum Dis 2009;68:400-3 «PMID: 19015209»PubMed
  200. Maxwell L, Singh JA. Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev 2009;:CD007277 «PMID: 19821401»PubMed
  201. Mazzantini M, Talarico R, Doveri M ym. Incident comorbidity among patients with rheumatoid arthritis treated or not with low-dose glucocorticoids: a retrospective study. J Rheumatol 2010;37:2232-6 «PMID: 20843913»PubMed
  202. McCluggage LK, Scholtz JM. Golimumab: a tumor necrosis factor alpha inhibitor for the treatment of rheumatoid arthritis. Ann Pharmacother 2010;44:135-44 «PMID: 20118145»PubMed
  203. McQueen FM, Stewart N, Crabbe J ym. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset. Ann Rheum Dis 1998;57:350-6 «PMID: 9771209»PubMed
  204. Moreland LW, O'Dell JR, Paulus HE ym. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum 2012;64:2824-35 «PMID: 22508468»PubMed
  205. Moulis G, Sommet A, Béné J ym. Cancer risk of anti-TNF-a at recommended doses in adult rheumatoid arthritis: a meta-analysis with intention to treat and per protocol analyses. PLoS One 2012;7:e48991 «PMID: 23155441»PubMed
  206. Munro R, Hampson R, McEntegart A ym. Improved functional outcome in patients with early rheumatoid arthritis treated with intramuscular gold: results of a five year prospective study. Ann Rheum Dis 1998;57:88-93 «PMID: 9613337»PubMed
  207. Mäkinen H, Kautiainen H, Hannonen P ym. Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis. J Rheumatol 2007;34:316-21 «PMID: 17183623»PubMed
  208. Möttönen TT, Hannonen P, Toivanen J ym. Value of joint scintigraphy in the prediction of erosiveness in early rheumatoid arthritis. Ann Rheum Dis 1988;47:183-9 «PMID: 3355257»PubMed
  209. Nam JL, Ramiro S, Gaujoux-Viala C ym. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2014;73:516-28 «PMID: 24399231»PubMed
  210. Nell VP, Machold KP, Eberl G ym. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford) 2004;43:906-14 «PMID: 15113999»PubMed
  211. O'Dell JR, Mikuls TR, Taylor TH ym. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med 2013;369:307-18 «PMID: 23755969»PubMed
  212. Ogata A, Tanimura K, Sugimoto T ym. Phase III study of the efficacy and safety of subcutaneous versus intravenous tocilizumab monotherapy in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken) 2014;66:344-54 «PMID: 23983039»PubMed
  213. Paimela L. The radiographic criterion in the 1987 revised criteria for rheumatoid arthritis. Reassessment in a prospective study of early disease. Arthritis Rheum 1992;35:255-8 «PMID: 1536665»PubMed
  214. Pavy S, Constantin A, Pham T ym. Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion. Joint Bone Spine 2006;73:388-95 «PMID: 16626993»PubMed
  215. Penesová A, Rádiková Z, Vlcek M ym. Chronic inflammation and low-dose glucocorticoid effects on glucose metabolism in premenopausal females with rheumatoid arthritis free of conventional metabolic risk factors. Physiol Res 2013;62:75-83 «PMID: 23173679»PubMed
  216. Puolakka K, Kautiainen H, Möttönen T ym. Predictors of productivity loss in early rheumatoid arthritis: a 5 year follow up study. Ann Rheum Dis 2005;64:130-3 «PMID: 15608311»PubMed
  217. Rantalaiho V, Kautiainen H, Korpela M ym. Physicians' adherence to tight control treatment strategy and combination DMARD therapy are additively important for reaching remission and maintaining working ability in early rheumatoid arthritis: a subanalysis of the FIN-RACo trial. Ann Rheum Dis 2014;73:788-90 «PMID: 24297374»PubMed
  218. Rembe EC. Use of cryotherapy on the postsurgical rheumatoid hand. Phys Ther 1970;50:19-23 «PMID: 5414653»PubMed
  219. Riemsma RP, Taal E, Kirwan JR ym. Systematic review of rheumatoid arthritis patient education. Arthritis Rheum 2004;51:1045-59 «PMID: 15593105»PubMed
  220. Roubille C, Richer V, Starnino T ym. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis 2015;74:480-9 «PMID: 25561362»PubMed
  221. Ruiz Garcia V, Jobanputra P, Burls A ym. Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. Cochrane Database Syst Rev 2011;:CD007649 «PMID: 21328299»PubMed
  222. Salliot C, Dougados M, Gossec L. Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials. Ann Rheum Dis 2009;68:25-32 «PMID: 18203761»PubMed
  223. Santiago T, da Silva JA. Safety of low- to medium-dose glucocorticoid treatment in rheumatoid arthritis: myths and reality over the years. Ann N Y Acad Sci 2014;1318:41-9 «PMID: 24814757»PubMed
  224. Scheel AK, Schmidt WA, Hermann KG ym. Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR "Train the trainers" course. Ann Rheum Dis 2005;64:1043-9 «PMID: 15640263»PubMed
  225. Schiff MH, Jaffe JS, Freundlich B. Head-to-head, randomised, crossover study of oral versus subcutaneous methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of oral methotrexate at doses =15 mg may be overcome with subcutaneous administration. Ann Rheum Dis 2014;73:1549-51 «PMID: 24728329»PubMed
  226. Schipper LG, Fransen J, den Broeder AA ym. Time to achieve remission determines time to be in remission. Arthritis Res Ther 2010;12:R97 «PMID: 20487520»PubMed
  227. Schoels MM, van der Heijde D, Breedveld FC ym. Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement. Ann Rheum Dis 2013;72:583-9 «PMID: 23144446»PubMed
  228. Scirè CA, Lunt M, Marshall T ym. Early remission is associated with improved survival in patients with inflammatory polyarthritis: results from the Norfolk Arthritis Register. Ann Rheum Dis 2014;73:1677-82 «PMID: 23749581»PubMed
  229. Scirè CA, Verstappen SM, Mirjafari H ym. Reduction of long-term disability in inflammatory polyarthritis by early and persistent suppression of joint inflammation: results from the Norfolk Arthritis Register. Arthritis Care Res (Hoboken) 2011;63:945-52 «PMID: 21337726»PubMed
  230. Scott DL, Ibrahim F, Farewell V ym. Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial. BMJ 2015;350:h1046 «PMID: 25769495»PubMed
  231. Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis. Cochrane Database Syst Rev 2010;:CD008331 «PMID: 20614469»PubMed
  232. Singh JA, Christensen R, Wells GA ym. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Cochrane Database Syst Rev 2009;:CD007848 «PMID: 19821440»PubMed
  233. Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis: a systematic review. J Rheumatol 2010;37:1096-104 «PMID: 20436075»PubMed
  234. Singh JA, Wells GA, Christensen R ym. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev 2011;:CD008794 «PMID: 21328309»PubMed
  235. Smith HJ. Contrast-enhanced MRI of rheumatic joint disease. Br J Rheumatol 1996;35 Suppl 3:45-7 «PMID: 9010090»PubMed
  236. Soini I, Kotaniemi A, Kautiainen H ym. US assessment of hip joint synovitis in rheumatic diseases. A comparison with MR imaging. Acta Radiol 2003;44:72-8 «PMID: 12631003»PubMed
  237. Stavropoulos-Kalinoglou A, Metsios GS, Veldhuijzen van Zanten JJ ym. Individualised aerobic and resistance exercise training improves cardiorespiratory fitness and reduces cardiovascular risk in patients with rheumatoid arthritis. Ann Rheum Dis 2013;72:1819-25 «PMID: 23155222»PubMed
  238. Steultjens EM, Dekker J, Bouter LM ym. Occupational therapy for rheumatoid arthritis. Cochrane Database Syst Rev 2004;:CD003114 «PMID: 14974005»PubMed
  239. Svensson B, Andersson ML, Bala SV ym. Long-term sustained remission in a cohort study of patients with rheumatoid arthritis: choice of remission criteria. BMJ Open 2013;3:e003554 «PMID: 24022393»PubMed
  240. Szkudlarek M, Narvestad E, Klarlund M ym. Ultrasonography of the metatarsophalangeal joints in rheumatoid arthritis: comparison with magnetic resonance imaging, conventional radiography, and clinical examination. Arthritis Rheum 2004;50:2103-12 «PMID: 15248207»PubMed
  241. Thompson AE, Rieder SW, Pope JE. Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients with early rheumatoid arthritis: a meta-analysis of randomized controlled trials. Arthritis Rheum 2011;63:1479-85 «PMID: 21360522»PubMed
  242. Tiippana-Kinnunen T, Laasonen L, Kautiainen H ym. Impact of early radiographic remission on the 15-year radiographic outcome in patients with rheumatoid arthritis. Scand J Rheumatol 2011;40:263-8 «PMID: 21417549»PubMed
  243. Tiippana-Kinnunen T, Paimela L, Kautiainen H ym. Can disease-modifying anti-rheumatic drugs be discontinued in long-standing rheumatoid arthritis? A 15-year follow-up. Scand J Rheumatol 2010;39:12-8 «PMID: 20132065»PubMed
  244. Toms TE, Panoulas VF, Douglas KM ym. Lack of association between glucocorticoid use and presence of the metabolic syndrome in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther 2008;10:R145 «PMID: 19091101»PubMed
  245. Tsakonas E, Fitzgerald AA, Fitzcharles MA ym. Consequences of delayed therapy with second-line agents in rheumatoid arthritis: a 3 year followup on the hydroxychloroquine in early rheumatoid arthritis (HERA) study. J Rheumatol 2000;27:623-9 «PMID: 10743799»PubMed
  246. van Aken J, Heimans L, Gillet-van Dongen H ym. Five-year outcomes of probable rheumatoid arthritis treated with methotrexate or placebo during the first year (the PROMPT study). Ann Rheum Dis 2014;73:396-400 «PMID: 23334213»PubMed
  247. van den Broek M, Huizinga TW, Dijkmans BA ym. Drug-free remission: is it already possible? Curr Opin Rheumatol 2011;23:266-72 «PMID: 21427578»PubMed
  248. van der Heide A, Jacobs JW, Bijlsma JW ym. The effectiveness of early treatment with "second-line" antirheumatic drugs. A randomized, controlled trial. Ann Intern Med 1996;124:699-707 «PMID: 8633829»PubMed
  249. van der Linden MP, le Cessie S, Raza K ym. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum 2010;62:3537-46 «PMID: 20722031»PubMed
  250. van der Woude D, Visser K, Klarenbeek NB ym. Sustained drug-free remission in rheumatoid arthritis after DAS-driven or non-DAS-driven therapy: a comparison of two cohort studies. Rheumatology (Oxford) 2012;51:1120-8 «PMID: 22337939»PubMed
  251. van Dongen H, van Aken J, Lard LR ym. Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2007;56:1424-32 «PMID: 17469099»PubMed
  252. van Nies JA, van der Helm-van Mil AH. Is early remission associated with improved survival or is arthritis persistency associated with increased mortality in early arthritis? Comparisons with the general population. Ann Rheum Dis 2013;72:e25 «PMID: 23852696»PubMed
  253. van Vollenhoven RF, Ernestam S, Geborek P ym. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet 2009;374:459-66 «PMID: 19665644»PubMed
  254. Ward MM, Leigh JP, Fries JF. Progression of functional disability in patients with rheumatoid arthritis. Associations with rheumatology subspecialty care. Arch Intern Med 1993;153:2229-37 «PMID: 8215726»PubMed
  255. Ward MM. Rheumatology visit frequency and changes in functional disability and pain in patients with rheumatoid arthritis. J Rheumatol 1997;24:35-42 «PMID: 9002008»PubMed
  256. Wassenberg S, Rau R, Zeidler H ym. A dose of only 5 mg prednisolone daily retards radiographic progression in early rheumatoid arthritis - the Low-Dose Prednisolone Trial. Clin Exp Rheumatol 2011;29:S68-72 «PMID: 22018187»PubMed
  257. Welch V, Brosseau L, Shea B ym. Thermotherapy for treating rheumatoid arthritis. Cochrane Database Syst Rev 2001;:CD002826 «PMID: 11406046»PubMed
  258. Verstappen SM, van Albada-Kuipers GA, Bijlsma JW ym. A good response to early DMARD treatment of patients with rheumatoid arthritis in the first year predicts remission during follow up. Ann Rheum Dis 2005;64:38-43 «PMID: 15130899»PubMed
  259. Wevers-de Boer K, Visser K, Heimans L ym. Remission induction therapy with methotrexate and prednisone in patients with early rheumatoid and undifferentiated arthritis (the IMPROVED study). Ann Rheum Dis 2012;71:1472-7 «PMID: 22402145»PubMed
  260. Wolfe F, Hawley DJ, Cathey MA. Clinical and health status measures over time: prognosis and outcome assessment in rheumatoid arthritis. J Rheumatol 1991;18:1290-7 «PMID: 1757927»PubMed
  261. Wong AK, Kerkoutian S, Said J ym. Risk of lymphoma in patients receiving antitumor necrosis factor therapy: a meta-analysis of published randomized controlled studies. Clin Rheumatol 2012;31:631-6 «PMID: 22147207»PubMed
  262. Woodburn J, Barker S, Helliwell PS. A randomized controlled trial of foot orthoses in rheumatoid arthritis. J Rheumatol 2002;29:1377-83 «PMID: 12136891»PubMed
  263. Yoo DH, Hrycaj P, Miranda P ym. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013;72:1613-20 «PMID: 23687260»PubMed

Suosituksen yhteyteen ei ole liitetty yhtään lisätieto-artikkelia tai linkkiä.

Daktyliitti
Daktyliitti