A Baseline Score to Predict Response to Ranibizumab Treatment in Neovascular Age-Related Macular Degeneration.
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ABSTRACT: Purpose
What are the patient characteristics predictive of response to ranibizumab treatment?Methods
Model-based characterization of best-corrected visual acuity (BCVA) time profiles of patients with neovascular age-related macular degeneration under ranibizumab or sham treatment based on 24-month observations of BCVA in 2419 patients from randomized multicenter phase 3 trials of ranibizumab: ANCHOR, MARINA, PIER, and HARBOR. Goodness-of-fit plots and precision of parameter estimates were used for measure of accuracy.Results
The model incorporates a long-term effect on disease progression and an additive and more potent short-term effect of ranibizumab. Response to ranibizumab treatment and progression of the disease were found to be a function of seven baseline characteristics (visual acuity, age, leakage size, central retinal lesion thickness, presence or absence of cyst, type of choroidal neovascularization (CNV), and size of pigment epithelium detachment). A composite score of these seven baseline characteristics was derived and used to categorize response to ranibizumab treatment. The ranibizumab treatment arms of two proof-of-concept studies held out from the model development were used to validate the methodology.Conclusions
A composite score based on seven patient characteristics prior to treatment could be used to discriminate patients with predicted insufficient response to anti-vascular endothelial growth factor treatment.Translational relevance
The method could be used to create a virtual ranibizumab treatment arm in clinical trials or to reduce the size of a ranibizumab active control arm.
SUBMITTER: Diack C
PROVIDER: S-EPMC8114000 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.).
| S-EPMC3157322 | biostudies-literature
Project description:ObjectiveTo determine the baseline predictors of visual acuity (VA) outcomes 1 year after treatment with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).DesignCohort study within the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).ParticipantsA total of 1105 participants with neovascular AMD, baseline VA 20/25 to 20/320, and VA measured at 1 year.MethodsParticipants were randomly assigned to ranibizumab or bevacizumab on a monthly or as-needed schedule. Masked readers evaluated fundus morphology and features on optical coherence tomography (OCT). Visual acuity was measured using electronic VA testing. Independent predictors were identified using regression techniques.Main outcome measuresThe VA score, VA score change from baseline, and ?3-line gain at 1 year.ResultsAt 1 year, the mean VA score was 68 letters, mean improvement from baseline was 7 letters, and 28% of participants gained ?3 lines. Older age, larger area of choroidal neovascularization (CNV), and elevation of retinal pigment epithelium (RPE) were associated with worse VA (all P<0.005), less gain in VA (all P<0.02), and a lower proportion gaining ?3 lines (all P<0.04). Better baseline VA was associated with better VA at 1 year, less gain in VA, and a lower proportion gaining ?3 lines (all P<0.0001). Predominantly or minimally classic lesions were associated with worse VA than occult lesions (66 vs. 69 letters; P=0.0003). Retinal angiomatous proliferans (RAP) lesions were associated with more gain in VA (10 vs. 7 letters; P=0.03) and a higher proportion gaining ?3 lines (odds ratio, 1.9; 95% confidence interval, 1.2-3.1). Geographic atrophy (GA) was associated with worse VA (64 vs. 68 letters; P=0.02). Eyes with total foveal thickness in the second quartile (325-425 ?m) had the best VA (P=0.01) and were most likely to gain ?3 lines (P=0.004). Predictors did not vary by treatment group.ConclusionsFor all treatment groups, older age, better baseline VA, larger CNV area, predominantly or minimally classic lesion, absence of RAP lesion, presence of GA, greater total fovea thickness, and RPE elevation on optical coherence tomography were independently associated with less improvement in VA at 1 year.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.
| S-EPMC3536921 | biostudies-literature
Project description:BACKGROUND/PURPOSE:Age-related macular degeneration (AMD) is the leading cause of visual impairment in patients over 55 years. Currently, the most common therapies for neovascular AMD (nAMD) are intravitreal antiangiogenics. Studies suggest that genetic factors influence on antiangiogenics therapy outcomes. The purpose of this work was to establish the association between complement factor H (CFH) (Y402H), age-related maculopathy susceptibility 2 (ARMS2) (A69S), and high-temperature requirement factor A1 (HTRA1) (rs11200638) polymorphisms and the response to treatment with ranibizumab in patients with nAMD. METHODS:A cross-sectional study with 61 eyes with nAMD treated with ranibizumab was performed. Association between polymorphisms from CFH, ARMS2, and HTRA1 with the response to treatment was established. RESULTS:The mean age of patients was 76.6 (51-91) years. Only 37.7% of patients had a functional response and 26.2% had an anatomic response. TT polymorphism Y402H from CFH gene was associated with an increased likelihood of functional response to treatment. Otherwise, there was not a statistically significant association between anatomic and functional response to gene polymorphisms rs11200638 from HTRA1 and rs10490924 from ARMS 2. CONCLUSIONS:This study suggests that the response to intravitreal antiangiogenic therapy with ranibizumab was not associated to main polymorphisms from genes HTRA1 and ARMS2. However, it was found that the response to treatment differed according to CFH genotype, suggesting that further investigations are needed to establish if patients with the CC and TC genotype may need to be monitored more closely for disease recurrence than the TT genotype.
| S-EPMC6947742 | biostudies-literature
Project description:To find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.
| S-EPMC8741927 | biostudies-literature
Project description:IntroductionNeovascular age-related macular degeneration (AMD) is the leading cause of severe, irreversible visual impairment in people over 60 years of age. Neovascular AMD is characterized by abnormal growth of blood vessels under the retina, specifically the macula. These vessels leak blood and fluids, damaging the retina and its photoreceptors, resulting in permanent loss of central vision. Vascular endothelial growth factor-A (VEGF-A) has been shown to play a critical role in the pathogenesis of neovascular AMD. In the US, ranibizumab, a VEGF-A blocker, is approved and indicated for the treatment of patients with neovascular AMD.AimsTo review the clinical evidence for ranibizumab in the treatment of neovascular AMD.Evidence reviewPhase III clinical trial data have established ranibizumab as a safe and well-tolerated treatment for neovascular AMD. Monthly intravitreal injections of ranibizumab result in a statistically significantly greater proportion of patients losing <15 letters of visual acuity (VA) and statistically significant increases in the mean number of letters gained compared with controls. Anatomically, ranibizumab results in stabilization in the mean area of choroidal neovascularization (CNV) and statistically significant reductions in the mean area of leakage compared with controls. Although there is limited economic evidence available, ranibizumab therapy for neovascular AMD appears to deliver a significant degree of value gain in terms of quality of life when compared with other neovascular AMD interventions.Place in therapyClinical evidence establishes ranibizumab as a first-line therapy option for virtually all treatable neovascular AMD patients. Updating neovascular AMD treatment guidelines to reflect the evidence base for ranibizumab as a preferred first-line therapy would be beneficial for physicians in making informed treatment choices and ultimately helping to ensure the best care for patients.
| S-EPMC3012443 | biostudies-literature
Project description:Purpose:The aim of this study was to evaluate whether indomethacin eye drops and intravitreal ranibizumab (IVR) injections would provide additional benefit over ranibizumab alone in the treatment of choroidal neovascularization (CNV). Participants and methods:This was a randomized, prospective pilot study of eyes with new-onset CNV. Fifty-eight patients were randomized 1:1 into a ranibizumab monotherapy (RM) group and a ranibizumab plus indomethacin (RI) group. All patients received monthly 0.5 mg IVR injections for 3 months, followed by monthly injections administered as needed. RI group patients also self-administered one drop of 0.5% indomethacin three times a day for 12 months. All patients were followed up for 12 months. Results:At 12 months, both groups showed significant improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). The mean BCVA change from baseline to 12 months was -0.12±0.04 LogMAR and -0.20±0.04 LogMAR in the RM and RI groups, respectively, with the degree of change being significantly different between the two groups (P=0.04). At 12 months, the mean CRT in the RM group (316±41.2 µm) was significantly higher than that in the RI group (287±31.5 µm; P=0.004). The mean required number of IVR injections was 7.38±0.78 and 6.34±0.67 in the RM and RI groups, respectively (P<0.001). Conclusion:Compared to IVR monotherapy, combination therapy with indomethacin eye drops and IVR provides superior anatomical and visual outcomes in patients with naive CNV lesions. Moreover, topical indomethacin might reduce the frequency of IVR injections, which is very beneficial considering the chronic and expensive nature of IVR therapy.
| S-EPMC5877501 | biostudies-literature
Project description:IntroductionThe aim of this study was to investigate the frequency and duration of missed hospital appointments (MHAs) in a consecutive cohort of patients treated with ranibizumab for neovascular age-related macular degeneration (nAMD) and to assess their impact on outcomes of therapy in a real-world clinical setting.MethodsRetrospective, cross-sectional study of consecutive patients attending medical retina clinics for nAMD treatment with ranibizumab.ResultsSeventy-eight eyes of 78 patients met the inclusion criteria for data analysis. Mean age was 78 years with mean follow-up of 27 months. Mean visual acuity (VA) was 52 ± 16 letters at baseline, 56 ± 17 letters at year 1 and 58 ± 16 letters at year 2. At the end of the second year, 90% of the patients had lost <15 letters, 26% had gained ≥15 letters and 10% had lost ≥15 letters. Nineteen patients had at least one MHA (24%) over 2 years. There were 26 MHA episodes in total leading to a median duration of 79 days (range 35-159) between attended hospital visits. None of these MHAs occurred during the first 3 months after treatment initiation. Mean VA and central retinal thickness difference between 2 years and baseline for the MHA group was not statistically different compared with the non-MHA group.ConclusionsOur data suggest that MHA may be a relatively common occurrence in AMD treatment clinics, but good outcomes of treatment can be achieved over 2 years despite missed hospital visits if patients are reviewed on average six times in the first year after an initial loading phase of three injections and nine times in the second year of treatment.
| S-EPMC4470979 | biostudies-literature
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.
| S-EPMC3389193 | biostudies-literature
Project description:IntroductionNeovascular age-related macular degeneration (nAMD) is the world's leading cause of blindness in elderly people. While anti-vascular endothelial growth factor (VEGF) treatments are used as the first option for patients with nAMD, they are generally expensive and need repeated injections. This study aimed to evaluate the cost-effectiveness of anti-VEGF therapies, focusing on the newly launched ranibizumab biosimilar (RBZ BS) in patients with nAMD from a Japanese societal perspective.MethodsA Markov model was developed to simulate the lifetime transitions of a cohort of treatment-naïve patients with nAMD through health states that were based on the involvement of nAMD (single eye vs. both eyes), the treatment status of the patients, and decimal best-corrected visual acuity. The model compared RBZ BS with branded RBZ, aflibercept (AFL), and AFL as loading dose switched to RBZ BS in maintenance in the treat-and-extend (TAE) regimen (RBZ TAE, AFL TAE, and AFL to RBZ BS TAE, respectively), and with branded RBZ in the pro re nata (PRN) regimen, as well as best supportive care (BSC). All processes were validated by five clinical experts.ResultsWhen TAE regimens were compared, RBZ BS was dominant (higher quality-adjusted life-years (QALYs) and lower total cost) to AFL TAE and AFL to RBZ TAE. The result was robust regardless of whether the clinical data were taken from the direct head-to-head clinical trial or from indirect treatment comparison. RBZ BS TAE was cost-saving compared to RBZ TAE. RBZ BS TAE was estimated to be dominant to BSC owing to a lower societal cost. Like TAE regimens, RBZ BS was cost-saving compared to RBZ PRN and was dominant to BSC in PRN regimens.ConclusionThis study suggests that RBZ BS is dominant to other anti-VEGF treatments in patients with nAMD in both TAE and PRN regimens and BSC from a Japanese societal perspective.
| S-EPMC10287869 | biostudies-literature
Project description:Introduction:To assess the ocular efficacy of intravitreal ranibizumab and conbercept injection in patients with neovascular age-related macular degeneration. Materials and methods:We searched PubMed, Wed of Science, Cochrane Library, EMBASE, Google Scholar, Medline, China National Knowledge Infrastructure, and WANFANG DATA databases, up to June 20, 2018. We also searched abstracts and clinical study presentations at meetings as well as trial registries; we contacted authors of included studies if questions arose. Eligibility criteria for selection of studies were randomized controlled trials and retrospective trials that compared ranibizumab with conbercept for treatment of neovascular age-related macular degeneration. Results:Eight randomized controlled trials and four retrospective studies were included with a total of 853 patients. Best-corrected visual acuity after loading dosage was improved in the conbercept group, compared with the ranibizumab group (weighted mean difference: -0.04; 95% CI: -0.07 to 0.00; P=0.04). There was a significant difference between conbercept and ranibizumab therapy with respect to unchanged or recurrent leakage of choroidal neovascularization (OR: 0.46; 95% CI: 0.24-0.88; P=0.02). No significant differences were observed in central macular thickness (weighted mean difference: -2.92; 95% CI: -9.00 to 3.17; P=0.35), complete and partial closure of leakage of choroidal neovascularization (complete closure, P=0.70; partial closure, P=0.35), or number of injections (weighted mean difference: 0.42; 95% CI: -0.46 to 1.29; P=0.35) between the conbercept and ranibizumab groups at the end of the follow-up periods. Conclusion:Pooled evidence confirmed that conbercept was superior to ranibizumab with respect to visual gain after treatment. Additional studies with long-term follow-up are needed to support our conclusion.
| S-EPMC6211581 | biostudies-other