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Background: Ofatumumab is approved for the treatment of relapsing multiple sclerosis (RMS). Ongoing safety reporting is crucial to understand its long-term benefit–risk profile. Objective: Report the safety and tolerability of ofatumumab in RMS after extended treatment up to 3.5 years. Methods: Patients completing ASCLEPIOS I/II (phase 3), APLIOS, or APOLITOS (phase 2) trials could enter ALITHIOS, a phase 3b, open-label, long-term safety study. We analyzed cumulative data of continuous ofatumumab treatment and of patients newly switched from teriflunomide. Results: The safety population had 1969 patients: 1292 continuously treated with ofatumumab (median time-at-risk 35.5 months, 3253 patient-years) and 677 newly switched (median time-at-risk 18.3 months, 986 patient-years). A total of 1650 patients (83.8%) had ⩾1 adverse events and 191 (9.7%) had ⩾1 serious adverse events. No opportunistic infections or progressive multifocal leukoencephalopathy events were identified; the risk of malignancies was low. Mean serum immunoglobulin (Ig) G levels remained stable. Mean IgM levels decreased but remained above the lower limit of normal in most. Serious infection incidence was low; decreased Ig levels were not associated with serious infections. Conclusion: In patients with up to 3.5 years’ exposure, ofatumumab was well tolerated, with no new safety risks identified. These findings, with its established effectiveness, support a favorable benefit–risk profile of ofatumumab in RMS.

Background: Ofatumumab, a fully human anti-CD20 monoclonal antibody indicated for the treatment of relapsing forms of multiple sclerosis (RMS), binds to a unique conformational epitope, thereby depleting B cells very efficiently and allowing subcutaneous administration at lower doses. Objectives: The aims were to characterize the relationship between ofatumumab concentration and B cell levels, including the effect of covariates such as body weight, age, or baseline B cell count, and use simulations to confirm the chosen therapeutic dose. Methods: Graphical and regression analyses previously performed based on data from a dose-range finding study provided the B cell depletion target used in the present work. All available adult phase 2/3 data for ofatumumab in RMS patients were pooled to develop a population pharmacokinetics (PK)–B cell count model, using nonlinear mixed-effects modeling. The population PK–B cell model was used to simulate B cell depletion and repletion times and the effect of covariates on PK and B cell metrics, as well as the dose response across a range of subcutaneous ofatumumab monthly doses. Results: The final PK–B cell model was developed using data from 1486 patients. The predetermined B cell target was best achieved and sustained with the 20-mg dose regimen, with median B cell count reaching 8 cells/µL in 11 days and negligible repletion between doses. Only weight had a significant effect on PK, which did not translate into any clinically relevant effect on B cell levels. Conclusion: The PK–B cell modeling confirms the dose chosen for the licensed ofatumumab regimen and demonstrates no requirement for dose adjustment based on adult patient characteristics.

Background: Few studies have investigated treatment options for patients with Alzheimer’s disease (AD) showing a poor response to oral cholinesterase inhibitors (ChEIs) in Japan. Objective: To investigate the efficacy and safety of switching from oral ChEIs to rivastigmine transdermal patch in patients with AD. Methods: In this multicenter, open-label, phase IV study in outpatient clinics in Japan, patients with mild-moderate AD who had a poor response to or experienced difficulty in continuing donepezil or galantamine were switched to rivastigmine transdermal patch (5 cm2; loaded dose 9 mg, delivery rate 4.6 mg/24 h) with a 1-step titration in week 4 (10 cm2; loaded dose 18 mg, delivery rate 9.5 mg/24 h), which was continued for 4 weeks in the titration period and 16 weeks in a maintenance period. The primary endpoint was the change in Mini-Mental State Examination (MMSE) total score from baseline to week 24. Results: A total of 118 patients were enrolled and switched to rivastigmine, of which 102 completed the 24-week study. The MMSE total score was essentially unchanged during the study, with a least-square mean change (SD) of −0.35 (2.64) at week 24 (p = 0.1750). Exploratory analysis with a mixed-effect model comparing changes in MMSE between the pre- and post-switch periods suggested that switching to rivastigmine prevented a worsening of MMSE. Application site skin reactions/irritations occurred in 30.5% of patients overall, in 22.0% in the 8-week titration period, and in 10.2% in the 16-week maintenance period. Conclusion: Within-class switching from an oral ChEI to rivastigmine transdermal patch might be an efficacious and tolerable option for AD patients showing a poor or limited response to a prior oral ChEI.

ObjectivesHere, we present the reported incidence rates of inflammatory bowel disease (IBD) in patients receiving treatment with secukinumab for psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), in a pooled analysis of 21 clinical trials.MethodsData from all patients who had received at least one dose of secukinumab were included. Safety analyses were conducted to evaluate cumulative IBD rates as well as per-year rates, by indication. Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) events were analysed using exposure-adjusted incidence rates (patient incidence rates per 100 patient-years (PY)).ResultsA total of 7355 patients with a cumulative exposure of 16 226.9 PY were included in the pooled analysis. Among 5181 patients with PsO, there were 14 cases of UC, 5 cases of CD and 1 case of IBDU, with exposure adjusted incidence rates (EAIRs) of 0.13, 0.05 and 0.01, respectively. Of these 20 cases, 14 were new-onset. In 1380 patients with PsA, there were 3 cases of UC, 3 cases of CD and 2 cases of IBDU (EAIRs 0.08, 0.08 and 0.05); 7 of these represented new-onset cases. Among 794 patients with AS, there were 4 cases of UC, 8 cases of CD and 1 case of IBDU (EAIRs 0.2, 0.4 and 0.1); 9 were new-onset cases. In the per year analysis, the EAIRs for each indication did not increase over time with secukinumab treatment.ConclusionsIn this pooled secukinumab safety analysis of 7355 patients across 21 clinical trials, cases of IBD events (including CD, UC and IBDU) were uncommon.

ObjectiveTo assess the long-term efficacy of ofatumumab treatment for up to ~4 years in patients with relapsing multiple sclerosis (RMS).MethodsThis analysis (data cut-off: 25-Sep-2021) will include cumulative data from patients randomised to ofatumumab/teriflunomide in the ASCLEPIOS I/II trials (core study) and the ongoing, open-label, ALITHIOS extension study. Patients will be analyzed in two groups: those randomised to ofatumumab in the core (continuous group) and those randomised to teriflunomide in the core with potential switch to ofatumumab in the extension (switch group). Annualised relapse rate (ARR), disability worsening (time- to-3-month/6-month confirmed disability worsening), disability improvement (time-to-6-month confirmed disability improvement), and brain MRI outcomes (number of Gd+T1 lesions and annualised T2 lesion rate) will be assessed.ResultsOverall, 1882 patients who were randomised in the ASCLEPIOS I/II trials (ofatumumab/terifluno- mide: 946/936) will be included in the analysis. In total, 690/946 patients treated with ofatumumab and 677/936 patients treated with teriflunomide entered ALITHIOS. Updated efficacy results for up to ~4 years will be presented at the congress.ConclusionsThese analyses will provide insights on the sustained efficacy of continuous ofatumumab treatment for up to 4 years in patients with RMS, and on ofatumumab efficacy in patients newly switched from teriflunomide. Funding: Novartis Pharma AG, Basel, Switzerland.

ObjectiveTo assess the efficacy of secukinumab on axial and peripheral enthesitis in patients with ankylosing spondylitis (AS) using pooled data from randomized controlled phase III studies.MethodsIn this posthoc analysis, data were pooled from patients originally randomized to secukinumab 150 mg, 300 mg, or placebo (PBO) from phase III MEASURE 1–4 studies (ClinicalTrials.gov: NCT01358175, NCT01649375, NCT02008916, and NCT02159053). Maastricht AS Enthesitis Score (MASES) was used for assessments of enthesitis through Week 52. Efficacy outcomes were mean change in MASES score and complete resolution (MASES = 0) of enthesitis in patients with baseline MASES > 0.ResultsA total of 693 (71.5%) patients had enthesitis at baseline in secukinumab 300 mg, 150 mg, and PBO groups (58 [76.3%], 355 [70.4%], and 280 [72%], respectively) out of 969 patients pooled in this analysis. At Week 16, mean changes from baseline for overall MASES and enthesitis at axial MASES sites, respectively, were as follows: –2.9 (P < 0.01) and –2.9 (P < 0.01) for secukinumab 300 mg; –2.4 (P < 0.015) and –2.3 (P < 0.05) for secukinumab 150 mg; and –1.9 and –1.8 for PBO, with improvements seen through Week 52. More than one-third of secukinumab-treated patients (300 mg: 36.2%; 150 mg: 40.8%) achieved complete resolution of enthesitis at Week 16.ConclusionSecukinumab improved enthesitis at overall MASES and axial sites in patients with AS.

Background Enthesitis can be a debilitating extra-articular spondyloarthritis manifestation that causes considerable pain and reduced quality of life. We evaluated the effect of secukinumab on axial and peripheral enthesitis in ankylosing spondylitis (AS) patients with baseline enthesitis (BLE) across all MASES sites (N = 13), axial MASES sites (N = 11; 13 MASES minus Achilles tendons [AT] [AxS]), peripheral sites (N = 6; AT + lateral condyles of humerus/femur [PS]) and the AT (N = 2) at Weeks 16 and 52. Methods This post-hoc analysis pooled data across four AS studies (MEASURE 1-4) from patients originally randomised to secukinumab 150 mg (approved AS dose), 300 mg (MEASURE 3 only) or placebo with BLE (MASES >0). Evaluations included mean change from baseline in MASES score, complete resolution (CR; MASES=0) and improvement from baseline in MASES score ≥5 counts. Mixed-effect model repeat measurement analysis was performed on change from baseline in MASES score and non-responder imputation for resolution of enthesitis at Week 16; data are reported as observed at Week 52. Results 355 (70.4%), 58 (76.3%) and 280 (72%) patients had BLE in the 150 mg, 300 mg and placebo groups, respectively. Baseline characteristics were comparable across groups. At Week 16, mean change from baseline for overall MASES and at AxS was greater for secukinumab 150 mg (−2.4, −2.3) and 300 mg (−2.9, −2.9) vs placebo (−1.9, −1.8; P < 0.05, P < 0.01). At Week 16, patients treated with secukinumab 150 mg (40.8%, 42.7%) and 300 mg (36.2%, 42.1%) vs placebo (28.9%, 30.1%) achieved CR of enthesitis at overall MASES and AxS. Secukinumab 150 mg and 300 mg were consistently associated with a higher mean change in MASES and CR of enthesitis at PS and AT vs placebo. More patients treated with secukinumab 150/300 mg vs placebo achieved a higher threshold of improvement (≥5 counts) in overall MASES at Week 16. Further improvements were observed for all endpoints at Week 52 (Table 1). Conclusion Secukinumab 150 mg and 300 mg were associated with a higher mean change in MASES and CR of enthesitis for overall MASES and at AxS vs placebo in AS patients at Week 16, which further improved through Week 52. Disclosures N. Barkham Grants/research support; Novartis, Eli Lilly, UCB, Celgene. G. Schett None. X. Baraliakos Consultancies; AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos. Member of speakers’ bureau; AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma. Grants/research support; AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer, Roche, UCB. F. van den Bosch Consultancies; AbbVie, Bristol-Myers Squibb, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, Pfizer, UCB. A. Deodhar Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, UCB. L.S. Gensler Consultancies; Novartis, Lilly, Janssen. Grants/research support; AbbVie, Amgen, UCB Pharma. M. Ǿstergaard Consultancies; AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, UCB. Member of speakers’ bureau; AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, UCB. Grants/research support; AbbVie, Celgene, Centocor, Merck, Novartis. S. Agawane Other; Employee of: Novartis. A. Das Gupta Other; Employee of: Novartis. S. Mpofu Other; Employee of: Novartis. T. Fox Other; Employee of: Novartis. A. Winseck Other; Employee of: Novartis. A. Shete Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. B. Porter Shareholder/stock ownership; Novartis. Other; Employee of: Novartis.

Purpose To evaluate the long-term (24-month) efficacy and safety of ranibizumab 0.5 mg administered pro re nata (PRN) with or without laser using an individualized visual acuity (VA) stabilization criteria in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). Design Phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study. Participants A total of 455 patients. Methods Patients were randomized (2:2:1) to ranibizumab 0.5 mg (n = 183), ranibizumab 0.5 mg with laser (n = 180), or laser (with optional ranibizumab 0.5 mg after month 6; n = 92). After initial 3 monthly injections, patients in the ranibizumab with or without laser arms received VA stabilization criteria-driven PRN treatment. Patients assigned to the laser arm received laser at the investigator's discretion. Main Outcome Measures Mean (and mean average) change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) from baseline to month 24, and safety over 24 months. Results A total of 380 patients (83.5%) completed the study. Ranibizumab with or without laser led to superior BCVA outcomes versus laser (monotherapy and combined with ranibizumab from month 6; 17.3/15.5 vs. 11.6 letters; P P P = 0.4259). A greater reduction in CSFT was seen with ranibizumab with or without laser versus laser monotherapy over 24 months from baseline (ranibizumab monotherapy −224.7 μm, ranibizumab with laser −248.9 μm, laser [monotherapy and combined with ranibizumab from month 6] −197.5 μm). Presence of macular ischemia did not affect BCVA outcome or treatment frequency. There were no reports of neovascular glaucoma or iris neovascularization. No new safety signals were identified. Conclusions The BRIGHTER study results confirmed the long-term efficacy and safety profile of PRN dosing driven by individualized VA stabilization criteria using ranibizumab 0.5 mg in patients with BRVO. Addition of laser did not lead to better functional outcomes or lower treatment need. The safety results were consistent with the well-established safety profile of ranibizumab.

Objective The objective of this study was to report the incidence of uveitis in secukinumab-treated patients with ankylosing spondylitis (AS) in a pooled analysis of three phase 3 trials (MEASURE 1-3 [ClinicalTrials.gov identifiers NCT01358175, NCT01649375, NCT02008916]). Methods Analysis included pooled patient-level data from all patients (N = 794) who received any dose (one or more) of secukinumab up to the last patient attending the week 156 study visit in MEASURE 1 and up to the week 156 visit in MEASURE 2 and the week 104 visit in MEASURE 3 for each patient. Postmarketing data were from the periodic safety update report. Incidence of uveitis is reported as the exposure-adjusted incidence rate (EAIR) per 100 patient-years of secukinumab exposure. Results Overall, 135 (17%) patients reported preexisting (but not active or ongoing) uveitis at baseline, and 589 (74.2%) patients were HLA antigen B27 positive. The EAIR for uveitis was 1.4 per 100 patient-years over the entire treatment period. Among all cases of uveitis (n = 26), 14 (54%) were flares. The exposure-adjusted reporting rate of uveitis in the postmarketing data (which included patients across the three approved indications of psoriasis, psoriatic arthritis, and AS) was 0.03 per 100 patient-years based on cumulative secukinumab exposure of 96 054 patient-years. Conclusion The incidence rate of uveitis in secukinumab-treated patients with active AS does not suggest an increased risk with secukinumab treatment.

Background Enthesitis can be a debilitating extra-articular spondyloarthritis (SpA) manifestation and cause of considerable pain and reduced quality of life/physical function.1,2 Objectives To evaluate the effect of secukinumab (SEC) on axial and peripheral enthesitis in ankylosing spondylitis (AS) patients (pts) with baseline enthesitis (BLE) across all Maastricht AS EnthesiS (MASES) sites (N=13), axial MASES sites [N=11; 13 MASES minus Achilles tendons (AT); AxS], peripheral sites (N=6; AT + lateral condyles of humerus/femur; PS) and the AT (N=2; AT) at Weeks (W) 16 and 52. Methods This post hoc analysis pooled data across 4 SEC studies in AS (MEASURE 1-4) from pts originally randomised to SEC 150mg (approved dose in AS), 300mg (MEASURE 3 only), or placebo (PBO) with BLE (MASES >0). Study designs have been reported previously. Evaluations include mean change from BL in MASES score, complete resolution (CR; MASES=0) and improvement from BL in MASES score of ≥5 counts. Mixed-effect model repeat measurement (MMRM) analysis was done on change from BL in MASES score and non-responder imputation for resolution of enthesitis at W16; data are reported as observed at W52. Results A total of 355 (70.4%), 58 (76.3%), and 280 (72%) pts had BLE in 150mg, 300mg and PBO groups, respectively. BL characteristics were generally comparable across groups. At W16, mean change from BL for overall MASES and at AxS was greater for SEC 150mg (-2.4 and -2.3) and 300mg (-2.9 and -2.9) vs PBO (-1.9 and -1.8; P Conclusion Secukinumab was associated with higher mean change in MASES and complete resolution of enthesitis compared to placebo at Week 16, which further improved through Week 52. References [1] Braun J, et al.Nat Clin Pract Rheumatol. 2006;2:536-45; 2. Schett G, et al. Nat Rev Rheumatol. 2017;13:731-741. Disclosure of Interests Georg Schett: None declared, Xenofon Baraliakos Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Pfizer, Merck Sharp & Dohme, UCB Pharma, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Atul Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Lianne S. Gensler Grant/research support from: Abbvie, Amgen, UCB Pharma , Consultant for: Novartis, Lilly, Janssen, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Shital Agawane Employee of: Novartis, Ayan Das Gupta Employee of: Novartis, Shephard Mpofu Employee of: Novartis, Todd Fox Employee of: Novartis, Adam Winseck Employee of: Novartis, Abhijit Shete Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, Brian Porter Shareholder of: Novartis, Employee of: Novartis

Background Secukinumab (SEC) has provided significant and sustained improvement in the signs and symptoms of active psoriatic arthritis (PsA) and ankylosing spondylitis 1. Evidence on the efficacy of biologics in the treatment of PsA patients (pts) with axial manifestations affecting 30–70% of PsA pts is limited2, particularly as validated classification criteria for this subtype of PsA are not yet available; an effort to develop criteria is being undertaken by ASAS/GRAPPA. MAXIMISE is an ongoing study evaluating the efficacy and safety of secukinumab 300 or 150mg in managing axial manifestations in PsA pts Objectives To report the primary analysis results at Week (Wk) 12 from MAXIMISE (NCT02721966) trial Methods This phase 3b, double blind, placebo (PBO)-controlled, multicentre 52-wk trial included 498 pts (aged ≥18 years) with PsA (CASPAR criteria), clinician-diagnosed axial involvements, spinal pain VAS >40/100 and BASDAI >4 despite trial of at least two NSAIDs. Pts were randomised to subcutaneous (SC) SEC (300/150 mg) or PBO weekly for 4 wks and every 4 wks thereafter. At Wk 12, PBO pts were re-randomised to SC SEC 300/150 mg. The primary endpoint was proportion of pts achieving ASAS20 response with SEC 300 mg at Wk 12. The key secondary endpoint was ASAS20 response with SEC 150 mg at Wk 12 after superiority of 300 mg was established. Analyses used multiple imputation Results Demographic and baseline (BL) disease characteristics were comparable across groups (Table). Primary and key secondary endpoints were met; ASAS20 response rates at Wk 12 were 63.1% (SEC 300 mg; P Conclusion MAXIMISE is the first randomised controlled trial evaluating the efficacy of a biologic in the management of the axial manifestations of PsA. SEC 300 and 150 mg provided rapid and significant improvement in ASAS20 responses through Wk 12 in PsA pts with axial manifestations and inadequate responses to NSAIDs References [1] Lubrano E and Perrotta FM. Ther Clin Risk Manag. 2016;12:1587-92 [2] Feld J, et al. Rheum Rev.2018;14:363 M, number of pts with available HLA-B27 status Disclosure of Interests Xenofon Baraliakos Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Pfizer, Merck Sharp & Dohme, UCB Pharma, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Laura C Coates Grant/research support from: AbbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead Sciences Inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB, Laure Gossec Grant/research support from: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Sanofi, and UCB, Consultant for: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, MSD, Nordic Pharma, Novartis-Sandoz, Pfizer, Roche, Sanofi, and UCB, Consultant for: L Gossec has received honoraria from Celgene as investigator for this study, Slawomir Jeka: None declared, ANTONIO MERA VARELA: None declared, Barbara Schulz Employee of: Novartis, Michael Rissler Employee of: Novartis, Ayan Das Gupta Employee of: Novartis, Chiara Perella Employee of: Novartis, Effie Pournara Shareholder of: Novartis, Employee of: Novartis

To assess the efficacy and safety profile of an individualized, stabilization criteria-driven regimen of ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to central retinal vein occlusion (CRVO).A 24-month, prospective, open-label, single-arm, multicenter study.A total of 357 patients.Patients received monthly ranibizumab 0.5 mg injections (minimum, 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg injections were administered if monitoring indicated a loss of VA due to disease activity. The primary outcome results have been published previously.Mean change from baseline at months 1 through 24 in best-corrected VA (BCVA) in the overall population and in subgroups categorized according to baseline BCVA, CRVO duration, or presence of macular ischemia.The baseline mean BCVA was 53.0 letters and baseline mean CRVO duration was 8.9 months (median, 2.4 months). The mean (standard deviation) gain in BCVA from baseline with ranibizumab 0.5 mg at month 24 was 12.1 (18.60) letters (P0.0001). Best-corrected VA gains at month 24 were similar in patients with or without baseline macular ischemia (mean change, 11.1 and 12.9 letters, respectively). The mean BCVA gain at month 24 was higher in patients with CRVO duration3 months (13.2 letters) compared with that in those with CRVO duration9 months (10.5 letters). Patients with lower baseline BCVA had larger mean BCVA gains at month 24 (≤39 letters; 18.5 letters) than those with higher baseline BCVA (40-59/≥60 letters; 13.9/7.2 letters), although the absolute BCVA values at month 24 were higher in patients with higher baseline BCVA. The mean (standard deviation) and median number of ranibizumab injections up to month 23 were 13.1 (6.39) and 15.0 injections, respectively. No new ocular or nonocular safety events were reported.An individualized, stabilization criteria-driven dosing regimen of ranibizumab 0.5 mg led to sustained BCVA gains for up to 24 months in patients with CRVO. The presence of macular ischemia at baseline did not influence VA gains. Shorter duration of CRVO at baseline was associated with better VA gains. Safety findings were consistent with those reported in previous ranibizumab studies in patients with CRVO.

To evaluate the long-term (24-month) efficacy and safety of ranibizumab 0.5 mg administered pro re nata (PRN) with or without laser using an individualized visual acuity (VA) stabilization criteria in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO).Phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study.A total of 455 patients.Patients were randomized (2:2:1) to ranibizumab 0.5 mg (n = 183), ranibizumab 0.5 mg with laser (n = 180), or laser (with optional ranibizumab 0.5 mg after month 6; n = 92). After initial 3 monthly injections, patients in the ranibizumab with or without laser arms received VA stabilization criteria-driven PRN treatment. Patients assigned to the laser arm received laser at the investigator's discretion.Mean (and mean average) change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) from baseline to month 24, and safety over 24 months.A total of 380 patients (83.5%) completed the study. Ranibizumab with or without laser led to superior BCVA outcomes versus laser (monotherapy and combined with ranibizumab from month 6; 17.3/15.5 vs. 11.6 letters; P0.0001). Ranibizumab with laser was noninferior to ranibizumab monotherapy (mean average BCVA change: 15.4 vs. 15.0 letters; P0.0001). However, addition of laser did not reduce the number of ranibizumab injections (mean injections: 11.4 vs. 11.3; P = 0.4259). A greater reduction in CSFT was seen with ranibizumab with or without laser versus laser monotherapy over 24 months from baseline (ranibizumab monotherapy -224.7 μm, ranibizumab with laser -248.9 μm, laser [monotherapy and combined with ranibizumab from month 6] -197.5 μm). Presence of macular ischemia did not affect BCVA outcome or treatment frequency. There were no reports of neovascular glaucoma or iris neovascularization. No new safety signals were identified.The BRIGHTER study results confirmed the long-term efficacy and safety profile of PRN dosing driven by individualized VA stabilization criteria using ranibizumab 0.5 mg in patients with BRVO. Addition of laser did not lead to better functional outcomes or lower treatment need. The safety results were consistent with the well-established safety profile of ranibizumab.