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Systemic adverse events after intravitreal bevacizumab versus ranibizumab for age-related macular degeneration: a meta-analysis.

ABSTRACT: OBJECTIVE: To assess whether the incidence of systemic adverse events differs between those who used bevacizumab and those who used ranibizumab in the treatment of age-related macular degeneration (AMD). METHODS: A systematic literature search was conducted to identify randomised controlled trials (RCTs) comparing the use of intravitreal bevacizumab with the use of ranibizumab in AMD patients. Results were expressed as risk ratios (RRs) with accompanying 95% confidence intervals (CIs). The data were pooled using the fixed-effect or random-effect model according to the heterogeneity present. RESULTS: Four RCTs were included in the final meta-analysis. Overall, the quality of the evidence was high. There were 2,613 treated patients: 1,291 treated with bevacizumab and 1,322 treated with ranibicizumab. No significant differences between bevacizumab use and ranizumab use were found in terms of the incidence of death from all causes, arteriothrombotic events, stroke, nonfatal myocardial infarction, vascular death, venous thrombotic events, and hypertension, with the pooled RRs being 1.11 (0.77, 1.61), 1.03 (0.69,1.55), 0.84 (0.39,1.80), 0.97 (0.48, 1.96), 1.24 (0.63, 2.44), 2.38 (0.94, 6.04), and 1.02 (0.29, 3.62), respectively. CONCLUSIONS: The meta-analysis shows that both treatments are comparably safe. However, the findings from our study must be confirmed in future research via well-designed cohort or intervention studies because of the limited number of studies.

SUBMITTER: Wang W

PROVIDER: S-EPMC4199620 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Systemic adverse events after intravitreal bevacizumab versus ranibizumab for age-related macular degeneration: a meta-analysis.

Wang Wei W Zhang Xiulan X

PloS one 20141016 10

<h4>Objective</h4>To assess whether the incidence of systemic adverse events differs between those who used bevacizumab and those who used ranibizumab in the treatment of age-related macular degeneration (AMD).<h4>Methods</h4>A systematic literature search was conducted to identify randomised controlled trials (RCTs) comparing the use of intravitreal bevacizumab with the use of ranibizumab in AMD patients. Results were expressed as risk ratios (RRs) with accompanying 95% confidence intervals (CI ...[more]

PMID: 25330364

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Project description:TOPIC:A comparison between ranibizumab and bevacizumab of the incidence of systemic serious adverse events (SAEs) among patients with neovascular age-related macular degeneration (nAMD) who participated in a large-scale randomized trial. Use of individual patient data, rather than aggregate data, allowed adjustment for strong predictors of SAEs. CLINICAL RELEVANCE:Relative safety of ranibizumab and bevacizumab is important in choosing an anti-VEGF drug for the hundreds of thousands of patients with nAMD treated each year worldwide. METHODS:Results of a Cochrane aggregate meta-analysis of the relative efficacy and safety of bevacizumab and ranibizumab that used searches of bibliographic databases and clinical trial registries as of March 14, 2014 and hand searching were reviewed to identify 6 large-scale, multicenter clinical trials. Individual patient data on SAEs, assigned drug and dosing regimen, and baseline prognostic factors were requested from the leaders of the 6 trials. A two-stage approach was used to estimate relative risks and 95% confidence intervals (CIs) from Cox proportional hazards models adjusting for baseline prognostic factors. The primary outcome measure was development of ?1 SAE; secondary outcome measures were death, arteriothrombotic events, events associated with systemic anti-VEGF therapy, and events not associated with systemic anti-VEGF therapy. RESULTS:Individual patient data were received from 5 trials to provide information on 3052 patients. There were no large imbalances between drug groups on baseline factors. The adjusted relative risk (95% CI) for bevacizumab relative to ranibizumab was 1.06 [(0.84, 1.35); p=0.61] for ?1 SAEs. For secondary outcomes, adjusted relative risks were 0.99 [ (0.69, 1.43); p=0.97] for death, 0.89 [ (0.62, 1.28); p=0.53] for arteriothrombotic events, 1.10 [ (0.81, 1.50); p=0.54] for events related to anti-VEGF treatment, and 1.11 [ (0.87, 1.40); p=0.40] for events not related to anti-VEGF treatment. CONCLUSION:Our findings support the absence of large differences in risk of systemic serious adverse events between these two anti-VEGF drugs; i.e., relative risks of ?1.5 are unlikely. Because additional head-to-head trials are unlikely, any further investigation of differential risk between anti-VEGF agents will only be achieved though post-marketing surveillance or through the interrogation of healthcare databases.

Project description:BACKGROUND:Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data. METHODS:In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart. RESULTS:Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 ?m) than in the other groups (152 to 168 ?m, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern. CONCLUSIONS:At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).

Project description:ObjectiveTo describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment.DesignMulticenter, randomized clinical trial.ParticipantsPatients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial.InterventionsAt enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) 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.Main outcome measuresMean change in visual acuity.ResultsAmong patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). 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). The proportion without fluid 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). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). 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). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).ConclusionsRanibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

Project description:BackgroundAnti-vascular endothelial growth factor (anti-VEGF) agents have become the standard of care in neovascular age-related macular degeneration (nAMD). Despite generally excellent response rates to anti-VEGF therapy, some patients do not respond or may respond suboptimally. In the case of refractory or rapidly recurring fluid in nAMD, clinicians may switch to another anti-VEGF agent. TITAN was an observational study that assessed the effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients with nAMD refractory to ranibizumab who switched to IVT-AFL after less than 12?months of ranibizumab treatment in routine clinical practice in France.MethodsTITAN was an observational, retrospective and prospective 12-month study conducted at 28 centres in France. Patients with nAMD refractory to ranibizumab were enrolled. Patients who were switched from ranibizumab to IVT-AFL were followed for 12?months. Data were obtained from medical records for retrospectively included patients, and at routine follow-up visits for those included prospectively. The main outcome measure was percentage of patients who achieved treatment success (gain of ?1 Early Treatment Diabetic Retinopathy Study letters in best-corrected visual acuity [BCVA] and/or any reduction in central retinal thickness [CRT]) from baseline to 12?months after switching. A sample size of 225 patients was determined based on a 2-sided 95% confidence interval with a width equal to 0.12 when the sample proportion was 0.70.ResultsWe analysed safety data (N =?217) and clinical outcomes from patients in the per-protocol population (n =?125). The mean (standard deviation) number of IVT-AFL injections was 7.5 (2.6). Treatment success was achieved in 68.8% of patients. Mean BCVA change from baseline to Month 12 was +?1.5 letters (P =?0.105) and the mean CRT change was -?45.0??m (P <? 0.001). In a subgroup analysis, in patients who received three initial monthly IVT-AFL injections, mean BCVA gain was 3.3 letters at Month 12 (P =?0.015). Excluding lack of efficacy and inappropriate scheduling of drug administration, the most common adverse event was eye pain (2.3%).ConclusionsSwitching ranibizumab-refractory patients with nAMD to IVT-AFL may improve visual outcomes in some patients, particularly those who receive three initial monthly injections.Trial registrationClinicalTrials.gov , NCT02321241 . First posted: December 22, 2014; Last update posted: July 2, 2018.

Dataset Information

Systemic adverse events after intravitreal bevacizumab versus ranibizumab for age-related macular degeneration: a meta-analysis.

Publications

Systemic adverse events after intravitreal bevacizumab versus ranibizumab for age-related macular degeneration: a meta-analysis.

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