KH2014 Suositus KH2014 Suositus

Tulosta

VEGF-estäjien hoitoprotokollat ja teho kosteaa silmänpohjarappeumaa sairastavilla

Näytönastekatsaukset
30.3.2016
Jorma Komulainen

Näytön aste: C

Bevasitsumabi ja ranibitsumabi annosteltuna 4–6 viikon välein ei ilmeisesti ole lyhyellä aikavälillä kliinisesti merkittävästi parempi kuin tarvittaessa annosteltuna näön paranemisen ja säilymisen suhteen kosteaa silmänpohjarappeumaa sairastavilla.

In the meta-analysis «Jiang S, Park C, Barner JC. Ranibizumab for age-related macular degeneration: a meta-analysis of dose effects and comparison with no anti-VEGF treatment and bevacizumab. J Clin Pharm Ther 2014;39:234-»1 ranibizumab and bevacizumab treatment regimens (monthly or as-needed/quarterly) were compared. Altogether 8 studies fulfilled the criteria and were included in the analysis. The dependent variable was visual acuity outcome, which was defined as either the effect size of letters gained (continuous) or whether or not a patient gained ≥ 15 letters in visual acuity (dichotomous). Minimum follow-up period was 12 months. The weighted regression on the 13 sets of comparisons revealed that patients with monthly treatment regimens had higher visual acuity gains compared with patients in the as needed/quarterly treatment group. (β = 0.441, P < 0.05). Also, more patients on the monthly treatment regimen gained ≥15 letters than patients treated on the as-needed/quarterly regimen (β = 0.582, P < 0.05).

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

Comment: There was a great heterogeneity between the studies. IVAN and HABOR studies were not included in analysis.

In the HARBOR study «Busbee BG, Ho AC, Brown DM ym. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 2013;120:1046-56 »2 1098 patients with subfoveal wet age-related macular degeneration (AMD) were randomized to get ranibizumab 0.5 mg or 2.0 mg intravitreal injections administered monthly or on a pro re nata (PRN) basis after 3 monthly loading doses for 12 months. Primary end point was mean change from baseline in best corrected visual acuity (BCVA) at month 12. Secondary end points were mean number of ranibizumab injections, mean change from baseline in central foveal thickness (CFT) over time and proportion of patients who gained at least 15 letters of BCVA. Neither statistically significant differences between the four groups were demonstrated in primary nor in secondary end points.

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

The 24 months follow-up results from the HARBOR study «Ho AC, Busbee BG, Regillo CD ym. Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 2014;121:2»3 showed no statistically significant differences between the above-mentioned groups. The proportion of patients who gained 15 letters in BCVA from baseline (i.e., 3-line gainers using the ETDRS chart) at month 24 was 34.5%, 33.1%, 37.6%, and 34.5% in the 0.5 mg monthly, 0.5 mg PRN, 2.0 mg monthly, and 2.0 mg PRN groups, respectively. During year 1, the ranibizumab monthly dosed groups averaged 11.3 (0.5 mg) and 11.2 (2.0 mg) injections, whereas the ranibizumab PRN-dosed groups averaged 7.7 (0.5 mg) and 6.9 (2.0 mg) injections. During year 2, the ranibizumab monthly dosed groups averaged 10.1 (0.5 mg) and 10.4 (2.0 mg) injections, and the ranibizumab PRN-dosed groups averaged 5.6 (0.5 mg) and 4.3 (2.0 mg) injections.

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

In the CATT study «Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG ym. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degenerat»4, 1185 patients with neovascular AMD were initially enrolled in the clinical trial, whereas 1107 of them were followed-up for 2 years. Patients were randomized in 4 groups: ranibizumab 0.5 mg or bevacizumab 1.25 mg and dosing regimen monthly or as needed. At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. Primary end point was mean change in visual acuity. Secondary end points were: proportion of patients with a change in visual acuity of ≥15 letters, number of injections, drug costs, presence of fluid and change in foveal retinal thickness, change in lesion size on fluorescein angiography and incidence of systemic and ocular adverse events.

Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; p=0.046). After adjusting for baseline predictors of visual acuity in a multivariable longitudinal regression model, the estimated change in visual acuity, averaged over 2 years of follow-up, was 1.7 letters better for patients treated monthly (CI: [−0.1, 3.4]; p=0.07).

The mean (standard deviation) number of injections through year 2 in the as-needed groups, out of a maximum of 26, was 12.6 (6.6) for patients treated with ranibizumab and 14.1 (7.0) for those treated with bevacizumab (p=0.01). The estimated 2-year drug cost per patient varied from $705 in the bevacizumab-as-needed group to $44.800 in the ranibizumab-monthly group. At 2 years, mean retinal thickness was 29 µm less in patients treated monthly than in patients treated with an as-needed regimen (regimen p=0.005).

The proportion of patients without fluid on OCT ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab-monthly group (drug p=0.0003; regimen p<0.0001). Fluorescein dye leakage was absent in a higher percentage of patients treated monthly than in patients treated as needed (regimen p=0.002).

The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07–1.57; p=0.009). Patients treated as needed had higher rates than patients treated monthly (risk ratio 1.20; CI: [0.98, 1.47]; p=0.08).

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

One hundred twenty eyes of 120 patients with treatment-naïve subfoveal neovascular AMD were randomized to receive either fixed-interval dosing (every 4 to 6 weeks) or variable dosing with intravitreal bevacizumab 1.25 mg for 12 months «El-Mollayess GM, Mahfoud Z, Schakal AR ym. Fixed-interval versus OCT-guided variable dosing of intravitreal bevacizumab in the management of neovascular age-related macular degeneration: a 12-month ra»5. Primary end point was best-corrected visual acuity. Secondary end point was central retinal thickness. No differences between groups were found.

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: hyvä

A total of 191 patients with exudative AMD were randomized to receive 1-year continuous regimen of intravitreal bevacizumab every 4, 6 or 8 weeks «Lushchyk T, Amarakoon S, Martinez-Ciriano JP ym. Bevacizumab in age-related macular degeneration: a randomized controlled trial on the effect of injections every 4 weeks, 6 weeks and 8 weeks. Acta Oph»6. Primary end point was visual acuity change after 1 year of treatment. Secondary end points were change in fluid and foveal thickness and proportion of patients with a change in visual acuity of 15 letters or more. There was no statistically significant difference in the mean change of visual acuity score at 1 year for bevacizumab administered every 4 (1.96 +/- 13.70), 6 (1.60 +/- 10.98) or 8 weeks (5.98 +/- 8.88), nor were there any differences in secondary end points.

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: hyvä

A total of 353 patients with primary or recurrent subfoveal CNV secondary to AMD were randomized to receive 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised of a loading phase (3 consecutive monthly injections) followed by a 9-month maintenance phase (either monthly or quarterly injection) «Schmidt-Erfurth U, Eldem B, Guymer R ym. Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. Ophthalmology 2011;118»7. Primary end point was mean change in best-corrected visual acuity (BCVA). Secondary end points were central retinal thickness (CRT) and incidence of adverse events (AEs). In the per-protocol population (293 patients), BCVA, measured by Early Treatment Diabetic Retinopathy Study-like charts, increased from baseline to month 12 by 4.9, 3.8, and 8.3 letters in the 0.3 mg quarterly (104 patients), 0.5 mg quarterly (88 patients), and 0.3 mg monthly (101 patients) dosing groups, respectively. Similar results were observed in the intent-to-treat (ITT) population (353 patients). Thus, the non-inferiority of a quarterly regimen was not achieved with reference to 5.0 letters. The mean decrease in CRT from baseline to month 12 in the ITT population was -96.0 µm in 0.3 mg quarterly, -105.6 µm in 0.5 mg quarterly, and -105.3 µm in 0.3 mg monthly group. The most frequent ocular AEs were conjunctival hemorrhage (17.6%, pooled quarterly groups; 10.4%, monthly group) and eye pain (15.1%, pooled quarterly groups; 20.9%, monthly group).

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: hyvä

Tämä teksti on linkitetty seuraaviin artikkeleihin:

  • Kostea silmänpohjan ikärappeuma (AMD) 1

Kirjallisuutta

  1. Jiang S, Park C, Barner JC. Ranibizumab for age-related macular degeneration: a meta-analysis of dose effects and comparison with no anti-VEGF treatment and bevacizumab. J Clin Pharm Ther 2014;39:234-9 «PMID: 24635444»PubMed
  2. Busbee BG, Ho AC, Brown DM ym. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 2013;120:1046-56 «PMID: 23352196»PubMed
  3. Ho AC, Busbee BG, Regillo CD ym. Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 2014;121:2181-92 «PMID: 25015215»PubMed
  4. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG ym. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology 2012;119:1388-98 «PMID: 22555112»PubMed
  5. El-Mollayess GM, Mahfoud Z, Schakal AR ym. Fixed-interval versus OCT-guided variable dosing of intravitreal bevacizumab in the management of neovascular age-related macular degeneration: a 12-month randomized prospective study. Am J Ophthalmol 2012;153:481-489.e1 «PMID: 22014603»PubMed
  6. Lushchyk T, Amarakoon S, Martinez-Ciriano JP ym. Bevacizumab in age-related macular degeneration: a randomized controlled trial on the effect of injections every 4 weeks, 6 weeks and 8 weeks. Acta Ophthalmol 2013;91:e456-61 «PMID: 23773796»PubMed
  7. Schmidt-Erfurth U, Eldem B, Guymer R ym. Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. Ophthalmology 2011;118:831-9 «PMID: 21146229»PubMed
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