Predictors of Early Diabetic Retinopathy Regression with Ranibizumab in the RIDE and RISE Clinical Trials.
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ABSTRACT: Purpose
To investigate the predictors of early diabetic retinopathy (DR) improvement in the RIDE/RISE (NCT00473382/NCT00473330) clinical trials.Patients and methods
In RIDE/RISE, adult patients with vision loss due to diabetic macular edema (DME) were randomized to monthly intravitreal ranibizumab 0.3 or 0.5 mg (n=502 total) or sham (n=257). DR severity was graded (using the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale). In this post hoc analysis of RIDE/RISE, eyes with baseline DR score ≥35 were evaluated for ≥2-step improvements, and eyes with baseline DR score ≥43 were evaluated for ≥3-step improvements. The characteristics associated with ≥2- or ≥3-step DR improvement at months 3 or 6 were assessed using univariate and/or multivariable analyses.Results
The percentage of eyes with a ≥2- or ≥3-step DR improvement was 20.1% and 3.7% at month 3 and 31.2% and 5.8% at month 6. Odds of ≥2-step DR improvement at months 3 or 6 were significantly greater in eyes with moderately severe to severe nonproliferative DR (NPDR) at baseline versus less severe or more severe DR (both P<0.0001). At month 6, odds of ≥2-step DR improvement were significantly greater in eyes with no DME at month 3 (P=0.008). Most patients with ≥3-step DR improvement at months 3 or 6 had proliferative DR (PDR) at baseline (83.3% and 66.7%).Conclusion
The strongest predictors of DR response to ranibizumab at month 6 were baseline DR severity and DME quiescence at month 3. Eyes with the most robust early improvements had moderately severe or severe NPDR or PDR at baseline.
SUBMITTER: Singer M
PROVIDER: S-EPMC7306476 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Predictors of Early Diabetic Retinopathy Regression with Ranibizumab in the RIDE and RISE Clinical Trials.
Singer Michael M Liu Mimi M Schlottmann Patricio G PG Khanani Arshad M AM Hemphill Miranda M Hill Lauren L Tuomi Lisa L Haskova Zdenka Z
Clinical ophthalmology (Auckland, N.Z.) 20200617
<h4>Purpose</h4>To investigate the predictors of early diabetic retinopathy (DR) improvement in the RIDE/RISE (NCT00473382/NCT00473330) clinical trials.<h4>Patients and methods</h4>In RIDE/RISE, adult patients with vision loss due to diabetic macular edema (DME) were randomized to monthly intravitreal ranibizumab 0.3 or 0.5 mg (n=502 total) or sham (n=257). DR severity was graded (using the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale). In this post hoc analysis ...[more]
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Project description:ImportancePanretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME).ObjectiveTo evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy.Design, setting, and participantsRandomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015.InterventionsIndividual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME.Main outcomes and measuresThe primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization.ResultsMean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified.Conclusions and relevanceAmong eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy.Trial registrationclinicaltrials.gov Identifier: NCT01489189.
| S-EPMC5567801 | biostudies-literature
Project description:ImportanceThe Diabetic Retinopathy Clinical Research Network Protocol S randomized clinical trial results suggest that ranibizumab is a reasonable treatment alternative to panretinal photocoagulation (PRP) when managing proliferative diabetic retinopathy (PDR), with or without concomitant baseline diabetic macular edema (DME). However, ranibizumab injections are costly. Thus, it would be useful to examine the relative cost-effectiveness of these 2 treatment modalities.ObjectiveTo evaluate incremental cost-effectiveness ratios of 0.5-mg ranibizumab therapy vs PRP for PDR.Design, setting, and participantsPreplanned secondary analysis using efficacy, safety, and resource utilization data through 2 years of follow-up at 55 US sites for 213 adults with PDR. Data were collected from February 2012 to January 2015.InterventionsIntravitreous 0.5-mg ranibizumab at baseline and as frequently as every 4 weeks based on a structured retreatment protocol or PRP at baseline for PDR. Eyes in both groups could receive ranibizumab for concomitant DME.Main outcomes and measuresIncremental cost-effectiveness ratios of ranibizumab compared with PRP evaluated within 2 prespecified subgroups for the study eye: with baseline vision-impairing (Snellen equivalent 20/32 or worse) DME and without baseline vision-impairing DME.ResultsThe study included 305 adults with PDR, the mean age was 52 years, 44% were women, and 52% were white. Of the 46 participants with PDR and vision-impairing DME at baseline, 21 were assigned to the ranibizumab group and 25 to the PRP group (plus ranibizumab for DME). Among the remaining participants without baseline vision-impairing DME, 80 and 87 were in the ranibizumab and PRP groups, respectively. For participants with and without baseline vision-impairing DME, the incremental cost-effectiveness ratios of ranibizumab therapy compared with PRP were $55 568/quality-adjusted life-year and $662 978/quality-adjusted life-year, respectively, over 2 years.Conclusions and relevanceOver 2 years, compared with PRP, 0.5-mg ranibizumab as given in this trial is within the $50 000/quality-adjusted life-year to $150 000/quality-adjusted life-year range frequently cited as cost-effective in the United States for eyes presenting with PDR and vision-impairing DME, but not for those with PDR without vision-impairing DME.Trial registrationClinicaltrials.gov Identifier: NCT01489189.
| S-EPMC5540054 | biostudies-literature
Project description:ImportanceVascular endothelial growth factor plays a role in proliferative diabetic retinopathy (PDR). Intravitreal injection of saline has been shown potentially to lead to improved visual acuity compared with observation alone in eyes with vitreous hemorrhage. Therefore, it is important to determine if intravitreal anti-vascular endothelial growth factor can reduce vitrectomy rates (and risks associated with vitrectomy) compared with saline for vitreous hemorrhage from PDR that precludes placement or confirmation of complete panretinal photocoagulation.ObjectiveTo evaluate intravitreal ranibizumab compared with intravitreal saline injections on vitrectomy rates for vitreous hemorrhage from PDR.DesignPhase 3, double-masked, randomized, multicenter clinical trial. Data reported were collected from June 2010 to March 2012 and include 16 weeks of follow-up.SettingCommunity-based and academic-based ophthalmology practices specializing in retinal diseases.ParticipantsTwo hundred sixty-one eyes of 261 study participants, who were at least 18 years of age with type 1 or type 2 diabetes mellitus. Study eyes had vitreous hemorrhage from PDR precluding panretinal photocoagulation completion.InterventionEyes were randomly assigned to 0.5-mg intravitreal ranibizumab (n = 125) or intravitreal saline (n = 136) at baseline and 4 and 8 weeks.Main outcome measureCumulative probability of vitrectomy within 16 weeks.ResultsCumulative probability of vitrectomy by 16 weeks was 12% with ranibizumab vs 17% with saline (difference, 4%; 95% CI, -4% to 13%) and of complete panretinal photocoagulation without vitrectomy by 16 weeks was 44% and 31%, respectively (P = .05). The mean (SD) visual acuity improvement from baseline to 12 weeks was 22 (23) letters and 16 (31) letters, respectively (P = .04). Recurrent vitreous hemorrhage occurred within 16 weeks in 6% and 17%, respectively (P = .01). One eye developed endophthalmitis after saline injection.Conclusions and relevanceOverall, the 16-week vitrectomy rates were lower than expected in both groups. This study suggests little likelihood of a clinically important difference between ranibizumab and saline on the rate of vitrectomy by 16 weeks in eyes with vitreous hemorrhage from PDR. Short-term secondary outcomes including visual acuity improvement, increased panretinal photocoagulation completion rates, and reduced recurrent vitreous hemorrhage rates suggest biologic activity of ranibizumab. Long-term benefits remain unknown. Whether vitrectomy rates after saline or ranibizumab injection are different than observation alone cannot be determined from this study.Trial registrationThe study is listed on www.clinicaltrials.gov, under identifier NCT00996437 (website registration date October 14, 2009).
| S-EPMC4217122 | biostudies-literature
Project description:PurposeTo compare patient-centered outcomes in patients with proliferative diabetic retinopathy (PDR) treated with ranibizumab vs panretinal photocoagulation (PRP).DesignRandomized clinical trial.MethodsSetting: Multicenter (55 U.S. sites).Patient populationTotal of 216 adults with 1 study eye out of 305 adults (excluding participants with 2 study eyes, because each eye received a different treatment) with PDR, visual acuity 20/320 or better, no history of PRP.InterventionRanibizumab (0.5 mg/0.05 mL) vs PRP.Main outcome measuresChange from baseline to 2 years in composite and prespecified subscale scores from the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), University of Alabama Low Luminance Questionnaire (UAB-LLQ), and Work Productivity and Activity Impairment Questionnaire (WPAIQ).ResultsFor the NEI VFQ-25 and UAB-LLQ composite scores, ranibizumab-PRP treatment group differences (95% CI) were +4.0 (-0.2, +8.3, P = .06) and +1.8 (-3.5, +7.1, P = 0.51) at 1 year, and +2.9 (-1.5, +7.2, P = .20) and +2.3 (-2.9, +7.5, P = .37) at 2 years, respectively. Work productivity loss measured with the WPAIQ was 15.6% less with ranibizumab (-26.3%, -4.8%, P = .005) at 1 year and 2.9% (-12.2%, +6.4%, P = .54) at 2 years. Eighty-three ranibizumab participants (97%) were 20/40 or better in at least 1 eye (visual acuity requirement to qualify for an unrestricted driver's license in many states) at 2 years compared with 82 PRP participants (87%, adjusted risk ratio = 1.1, 95% CI: 1.0, 1.2, P = .005).ConclusionsThough differences in some work productivity and driving-related outcomes favored ranibizumab over PRP, no differences between treatment regimens for PDR were identified for most of the other patient-centered outcomes considered.
| S-EPMC5215763 | biostudies-literature
Project description:ObjectiveTo determine the time to first clinically meaningful improvement in best-corrected visual acuity (BCVA) in patients treated with ranibizumab for diabetic macular oedema (DME) and identify predictors of early visual improvement.Methods and analysisWe retrospectively analysed the phase III RIDE (NCT00473382) and RISE (NCT00473330) trials, in which 759 patients with DME were randomised to monthly intravitreal ranibizumab 0.3 mg (n=250), ranibizumab 0.5 mg (n=252) or sham treatment (n=257). After month 24, 191 sham-treated patients crossed over to monthly ranibizumab 0.5 mg through month 36, while ranibizumab-treated patients continued treatment. Kaplan-Meier analyses assessed time to achieve ≥15 or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter gains from baseline or ≥20/40 Snellen equivalent BCVA in each treatment arm. Baseline predictors of ≥15 ETDRS letter gains at month 6 were identified by logistic regression.ResultsMedian time to first ≥15 ETDRS letter gain was significantly shorter in patients who received ranibizumab (0.3 mg, 11.1 months; 0.5 mg, 10.9 months) than sham-treated patients who crossed over to ranibizumab 0.5 mg at month 24 (35.7 months; both p<0.0001). Half of ranibizumab-treated patients achieved ≥20/40 BCVA within 2.3 (0.3 mg) and 1.9 months (0.5 mg). Baseline predictors of early vision improvement among ranibizumab-treated patients were BCVA ≤55 ETDRS letters, younger age and presence of subretinal fluid.ConclusionPrompt ranibizumab therapy for DME was associated with rapid, clinically meaningful vision gains that were maintained over 36 months of treatment. Lower BCVA, younger age and presence of subretinal fluid were predictive of early vision improvement.
| S-EPMC6830470 | biostudies-literature
Project description:ImportanceRanibizumab is a viable treatment option for eyes with proliferative diabetic retinopathy (PDR) through 2 years. However, longer-term results are needed.ObjectiveTo evaluate efficacy and safety of 0.5-mg intravitreous ranibizumab vs panretinal photocoagulation (PRP) over 5 years for PDR.Design, setting, and participantsDiabetic Retinopathy Clinical Research Network multicenter randomized clinical trial evaluated 394 study eyes with PDR enrolled February through December 2012. Analysis began in January 2018.InterventionsEyes were randomly assigned to receive intravitreous ranibizumab (n = 191) or PRP (n = 203). Frequency of ranibizumab was based on a protocol-specified retreatment algorithm. Diabetic macular edema could be managed with ranibizumab in either group.Main outcomes and measuresMean change in visual acuity (intention-to-treat analysis) was the main outcome. Secondary outcomes included peripheral visual field loss, development of vision-impairing diabetic macular edema, and ocular and systemic safety.ResultsThe 5-year visit was completed by 184 of 277 participants (66% excluding deaths). Of 305 enrolled participants, the mean (SD) age was 52 (12) years, 135 (44%) were women, and 160 (52%) were white. For the ranibizumab and PRP groups, the mean (SD) number of injections over 5 years was 19.2 (10.9) and 5.4 (7.9), respectively; the mean (SD) change in visual acuity letter score was 3.1 (14.3) and 3.0 (10.5) letters, respectively (adjusted difference, 0.6; 95% CI, -2.3 to 3.5; P = .68); the mean visual acuity was 20/25 (approximate Snellen equivalent) in both groups at 5 years. The mean (SD) change in cumulative visual field total point score was -330 (645) vs -527 (635) dB in the ranibizumab (n = 41) and PRP (n = 38) groups, respectively (adjusted difference, 208 dB; 95% CI, 9-408). Vision-impairing diabetic macular edema developed in 27 and 53 eyes in the ranibizumab and PRP groups, respectively (cumulative probabilities: 22% vs 38%; hazard ratio, 0.4; 95% CI, 0.3-0.7). No statistically significant differences between groups in major systemic adverse event rates were identified.Conclusions and relevanceAlthough loss to follow-up was relatively high, visual acuity in most study eyes that completed follow-up was very good at 5 years and was similar in both groups. Severe vision loss or serious PDR complications were uncommon with PRP or ranibizumab; however, the ranibizumab group had lower rates of developing vision-impairing diabetic macular edema and less visual field loss. Patient-specific factors, including anticipated visit compliance, cost, and frequency of visits, should be considered when choosing treatment for patients with PDR. These findings support either anti-vascular endothelial growth factor therapy or PRP as viable treatments for patients with PDR.Trial registrationClinicalTrials.gov Identifier: NCT01489189.
| S-EPMC6233839 | biostudies-literature
Project description:BackgroundTo evaluate the safety of ranibizumab as a surgical adjunct during cataract surgery in patients with proliferative diabetic retinopathy (PDR) with rubeosis, and to evaluate the efficacy and adverse effects of ranibizumab in treating PDR with rubeosis.Materials and methodsThree intravitreal injections of 0.5 mg ranibizumab were administered on day-1, months-1 and -2 with cataract surgery 6-16 days after first injection. Retreatments with ranibizumab injections and pan-retinal photocoagulation (PRP) were given if recurrence or persistence of PDR was noted between months-3 and -11. Safety observation visits occurred at months-12, -18 and -24. Primary end points were incidence and severity of adverse events (AEs) that were related to both cataract surgery and treatment of PDR with rubeosis through month -12.ResultsOf six patients screened, four (mean age 61.3 years) were enrolled. No AEs were noted with either cataract surgery or treatment of PDR. Neovascularization of iris (NVI) promptly regressed by 4 days after first ranibizumab injection, prior to cataract surgery in three of four patients (one had significantly regressed NVI by post-injection day-3 visit); NVI was not noted in any patient at 2 weeks after first ranibizumab injection. Recurrence of rubeosis or NVA after 3 monthly injections was not observed in any. At month-12, PDR was not present when assessed clinically and by fluorescein angiogram (FA). Only one patient developed neovascularization of disc and neovascularization elsewhere and required retreatments at months-5 and -9.ConclusionsMultiple intravitreal injections of ranibizumab may be a safe, effective treatment adjunct for PDR and diabetes-related rubeosis.
| S-EPMC3574511 | biostudies-literature
Project description:ImportanceAnti-vascular endothelial growth factor (VEGF) medicines have revolutionized diabetic macular edema (DME) treatment. A recent randomized clinical trial comparing anti-VEGF agents for patients with decreased vision from DME found that at 1 year aflibercept (2.0 mg) achieved better visual outcomes than repackaged (compounded) bevacizumab (1.25 mg) or ranibizumab (0.3 mg); the worse the starting vision, the greater the treatment benefit with aflibercept. However, aflibercept and ranibizumab, respectively, are approximately 31 and 20 times more expensive than bevacizumab.ObjectiveTo examine the incremental cost-effectiveness ratios (ICERs) of aflibercept, bevacizumab, and ranibizumab for the treatment of DME.Design, setting, and participantsPost hoc analysis of efficacy, safety, and resource utilization data at 1-year follow-up from the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness Trial. Patients were enrolled from August 22, 2012, through August 28, 2013, and analysis was performed from August 21, 2014, through November 7, 2015.Main outcomes and measuresThe ICERs for all trial participants and subgroups with baseline vision of approximate Snellen equivalent 20/32 to 20/40 (better vision) and baseline vision of approximate Snellen equivalent 20/50 or worse (worse vision). One-year trial data were used to calculate cost-effectiveness for 1 year for the 3 anti-VEGF agents; mathematical modeling was then used to project 10-year cost-effectiveness results.ResultsThe study included 624 participants (mean [SD] age, 60.6 [10.5] years; 45.7% female; 65.5% white), 209 in the aflibercept group, 207 in the bevacizumab group, and 208 in the ranibizumab group. For all participants, during 1 year, the ICERs of aflibercept and ranibizumab compared with bevacizumab were $1 110 000 per quality-adjusted life-year (QALY) and $1 730 000 per QALY, respectively. During 10 years, they were $349 000 per QALY and $603 000 per QALY, respectively. Compared with ranibizumab, aflibercept's ICER was $648 000 per QALY at 1 year and $203 000 per QALY at 10 years. For the subgroup with worse baseline vision, the 10-year ICERs of aflibercept and ranibizumab compared with bevacizumab were $287 000 per QALY and $817 000 per QALY, respectively. In eyes with decreased vision from DME, treatment costs of aflibercept and ranibizumab would need to decrease by 69% and 80%, respectively, to reach a cost-effectiveness threshold of $100 000 per QALY compared with bevacizumab during a 10-year horizon; for the subgroup with worse baseline vision, the costs would need to decrease by 62% and 84%, respectively.Conclusions and relevanceAflibercept (2.0 mg) and ranibizumab (0.3 mg) are not cost-effective relative to bevacizumab for treatment of DME unless their prices decrease substantially. These results highlight the challenges that physicians, patients, and policymakers face when safety and efficacy results are at odds with cost-effectiveness results.
| S-EPMC6648661 | biostudies-literature
Project description:ImportanceFrequent prophylactic intravitreal anti-vascular endothelial growth factor injections can reduce risk of progression to vision-threatening complications in nonproliferative diabetic retinopathy (NPDR). A refillable drug delivery system for continuous intraocular ranibizumab release could offer less frequent treatment regimens.ObjectiveTo evaluate the Port Delivery System (PDS) with ranibizumab, 100 mg/mL, with refill-exchange procedures every 36 weeks (PDS Q36W), vs no PDS (control) in moderately severe to severe NPDR without center-involved diabetic macular edema (CI-DME), monitoring both groups every 4 weeks.Design, setting, and participantsThis was a randomized clinical trial at 50 US investigational sites. Participants aged 18 years or older with moderately severe or severe NPDR (Diabetic Retinopathy Severity Scale [DRSS] level 47 or 53) secondary to type 1 or 2 diabetes were eligible. Data analysis was performed from August 10, 2020, to October 3, 2022.InterventionParticipants were randomized (unmasked) 5:3 to PDS Q36W vs control. Both groups could receive intravitreal ranibizumab injections if CI-DME, proliferative diabetic retinopathy (PDR), or anterior segment neovascularization (ASNV) developed.Main outcomes and measuresProportion of participants with an improvement of at least 2 levels in Early Treatment Diabetic Retinopathy Study DRSS from baseline at week 52.ResultsA total of 174 participants (mean [SD] age, 53.9 [11.7] years; 74 [42.5%] female) were randomized to PDS Q36W (n = 106) or control (n = 68). At week 52, 80.1% of those receiving PDS Q36W vs 9.0% of control participants had at least a 2-step DRSS improvement from baseline (difference, 71.1% [95% CI, 61.0% to 81.2%]; P < .001). Secondary outcomes included rate of development of CI-DME, PDR, or ASNV through week 52 (PDS Q36W, 7.1%; control, 47.0%; hazard ratio, 0.12 [95% CI, 0.05 to 0.28]; P < .001) and best-corrected visual acuity (BCVA) change from baseline to week 52 (+1.4 letters [95% CI, -0.5 to 3.3 letters] for those receiving PDS Q36W vs -2.6 letters [95% CI, -5.0 to -0.1 letters] for control participants; difference, 4.0 letters [95% CI, 0.9 to 7.1 letters]; P = .01). The PDS Q36W group had a transient BCVA decrease of 7.4 letters (95% CI, -10.3 to -4.5 letters) at 4 weeks after implantation, resolving 8 weeks later. Ocular adverse events of special interest occurred in 17 of 105 participants (16.2%) receiving PDS Q36W (cataract, 7 participants [6.7%]; vitreous hemorrhage, 6 participants [5.7%]; conjunctival bleb, conjunctival retraction, and hyphema, each 2 participants [1.9%]; conjunctival erosion and retinal detachment, each 1 participant [1.0%]), with no endophthalmitis reported through week 52.Conclusions and relevanceAt 1 year, PDS Q36W resulted in substantially more participants achieving at least a 2-step DRSS improvement and a reduced risk of developing CI-DME, PDR, or ASNV compared with control participants, with safety outcomes consistent with previous reports. These findings should be balanced with the transient, postoperative decrease in BCVA 4 through 12 weeks after implantation and the need for longer-term BCVA and safety outcomes.Trial registrationClinicalTrials.gov Identifier: NCT04503551.
| S-EPMC11886866 | biostudies-literature
Project description:ImportanceAnti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) favorably affects diabetic retinopathy (DR) improvement and worsening. It is unknown whether these effects differ across anti-VEGF agents.ObjectiveTo compare changes in DR severity during aflibercept, bevacizumab, or ranibizumab treatment for DME.Design, setting, and participantsPreplanned secondary analysis of data from a comparative effectiveness trial for center-involved DME was conducted in 650 participants receiving aflibercept, bevacizumab, or ranibizumab. Retinopathy improvement and worsening were determined during 2 years of treatment. Participants were randomized in 2012 through 2013, and the trial concluded on September 23, 2015.InterventionsRandom assignment to aflibercept, 2.0 mg; bevacizumab, 1.25 mg; ranibizumab, 0.3 mg, up to every 4 weeks through 2 years following a retreatment protocol.Main outcomes and measuresPercentages with retinopathy improvement at 1 and 2 years and cumulative probabilities for retinopathy worsening through 2-year without adjustment for multiple outcomes.ResultsA total of 650 participants (495 [76.2%] nonproliferative DR [NPDR], 155 proliferative DR [PDR]) were analyzed; 302 (46.5%) were women and mean (SD) age was 61 (10) years; 425 (65.4%) were white. At 1 year, among 423 NPDR eyes, 44 of 141 (31.2%) treated with aflibercept, 29 of 131 (22.1%) with bevacizumab, and 57 of 151 (37.7%) with ranibizumab had improvement of DR severity (adjusted difference: 11.7%; 95% CI, 2.9% to 20.6%; P = .004 for aflibercept vs bevacizumab; 8.9%; 95% CI, 1.7% to 16.1%; P = .01 for ranibizumab vs bevacizumab; and 2.9%; 95% CI, -5.7% to 11.4%; P = .51 for aflibercept vs ranibizumab). At 2 years, 33 eyes (24.8%) in the aflibercept group, 25 eyes (22.1%) in the bevacizumab group, and 40 eyes (31.0%) in the ranibizumab group had DR improvement; no treatment group differences were identified. For 93 eyes with PDR at baseline, 1-year improvement rates were 75.9% for aflibercept, 31.4% for bevacizumab, and 55.2% for ranibizumab (adjusted difference: 50.4%; 95% CI, 26.8% to 74.0%; P < .001 for aflibercept vs bevacizumab; 20.4%; 95% CI, -3.1% to 44.0%; P = .09 for ranibizumab vs bevacizumab; and 30.0%; 95% CI, 4.4% to 55.6%; P = .02 for aflibercept vs ranibizumab). These rates and treatment group differences appeared to be maintained at 2 years. Despite the reduced numbers of injections in the second year, 66 (59.5%) of NPDR and 28 (70.0%) of PDR eyes that manifested improvement at 1 year maintained improvement at 2 years. Two-year cumulative rates for retinopathy worsening ranged from 7.1% to 10.2% and 17.2% to 26.4% among anti-VEGF groups for NPDR and PDR eyes, respectively. No statistically significant treatment differences were noted.Conclusions and relevanceAt 1 and 2 years, eyes with NPDR receiving anti-VEGF treatment for DME may experience improvement in DR severity. Less improvement was demonstrated with bevacizumab at 1 year than with aflibercept or ranibizumab. Aflibercept was associated with more improvement at 1 and 2 years in the smaller subgroup of participants with PDR at baseline. All 3 anti-VEGF treatments were associated with low rates of DR worsening. These data provide additional outcomes that might be considered when choosing an anti-VEGF agent to treat DME.
| S-EPMC5540030 | biostudies-literature