Treatment of MOG-IgG-associated demyelination with Rituximab: a multinational study of 98 patients (S13.003)

Objective: To evaluate the effectiveness of Rituximab in preventing relapses of MOG-IgG-associated demyelination. Background: MOG-IgG-associated demyelination (MOG-D) is increasingly recognised, where diagnostic testing is available, as a distinct non-MS CNS demyelinating disease that shares many features with aquaporin-4-IgG-associated neuromyelitis optica spectrum disorders (AQP4-NMOSD). In retrospective series, Rituximab was shown to reduce relapses in AQP4-NMOSD by up to 80%. The efficacy of Rituximab in MOG-D is unknown. Design/Methods: Retrospective review of all Rituximab-treated MOG-D patients (n = 112) from 25 centres in Europe (16), USA (4), Argentina (1), Brazil (1), India (1), Korea (1) and Japan (1). Results: After excluding cases of diagnostic uncertainty (1), inadequate treatment (3) and incomplete data (10), 98 cases were analysed (59% female; median age at disease onset of 26.1years). Median disease duration prior to treatment was 19.5months and median time on Rituximab was 12.2months. 81 patients (83%) had relapsing disease prior to Rituximab treatment. 58 patients (59%) received Rituximab as first line therapy. For patients with relapsing disease prior to starting Rituximab (n = 81), there was a 42% reduction in relapse rate on Rituximab (95%CI=21–57%, p=0.001, Poisson regression). Median annualised relapse rates (for patients with a minimum duration of follow-up of 6months pre-and post-Rituximab, n = 51) fell from 0.9 (range 0.1–6.0) to 0.0 (range 0.0–4.0) (p=0.013, Wilcoxon SR test). Survival analysis predicts that 63% (95%CI=49–73%) and 35% (95%CI=19–49%) of Rituximab-treated patients will be relapse-free at one and three years respectively. Median time to first relapse on Rituximab (n = 39) was 5.0months (range 0.9–23.7 months). Some relapses occurred despite confirmed B-cell depletion. Of the 17 patients with only one event prior to starting Rituximab, 5 had at least one relapse on treatment with Rituximab. Conclusions: Rituximab treatment of MOG-D reduces relapse rates significantly. Compared to similar studies on AQP4-NMOSD, the benefit seems less marked and requires further study. Disclosure: Dr. Whittam has nothing to disclose. Dr. Cobo-Calvo has nothing to disclose. Dr. Lopez has nothing to disclose. Dr. Pardo has nothing to disclose. Dr. Dodd has nothing to disclose. Dr. Brandt has nothing to disclose. Dr. Berek has nothing to disclose. Dr. Berger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from Almirall, Biogen, Celgene, Genzyme, Merck, Novartis, Octapharma, Roche, Sanofi Adventist/TEVA. Dr. Berger has received research support from His institution has received financial support by unrestricted research grants (Biogen, Novartis, Roche, Sanofi Aventis/TEVA) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma,. Dr. Gombolay has nothing to disclose. Dr. Oliveira has nothing to disclose. Dr. Callegaro has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck, Roche, Genzyme. Dr. Kaneko has nothing to disclose. Dr. Misu has nothing to disclose. Dr. Brochet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Biogen-idec, Genzyme, Medday. Dr. Brochet has received research support from Teva, Biogen, Medday, Novartis, Roche, Actelion, Genzyme, Merck, Bayer. Dr. Audoin has nothing to disclose. Dr. Mathey has nothing to disclose. Dr. Laplaud has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Biogen, Roche, Merck. Dr. Laplaud has received research support from Novartis, Biogen, Roche, Merck. Dr. Thouvenot has nothing to disclose. Dr. Cohen has nothing to disclose. Dr. Tourbah has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, MedDay, Merck serono, Roche, Sanofi-Genzyme, Teva. Dr. Maillart has nothing to disclose. Dr. Ciron has nothing to disclose. Dr. Deschamps has nothing to disclose. Dr. Biotti has nothing to disclose. Dr. Matiello has nothing to disclose. Dr. Palace has nothing to disclose. Dr. Lim has nothing to disclose. Dr. Fujihara has nothing to disclose. Dr. Nakashima has nothing to disclose. Dr. Bennett has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting / advisory board: Genentech, MedImmune, EMD Serono, Teva Neuroscience, Genzyme. Dr. Bennett has received royalty, license fees, or contractual rights payments from Royalty payments for intellectual property on Aquaporumab. Dr. Bennett has received research support from EMD Serono. Dr. Pandit has nothing to disclose. Dr. Chitnis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, Novartis, Sanofi-Genzyme, Roche-Genentech. Dr. Weinshenker has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Alexion, MedImmune, Caladrius Biosciences, Brainstorm Therapeutics. Dr. Wildemann has nothing to disclose. Dr. Sato has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Reindl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Speaker honoraria and compensation of travel costs from Chugai. Dr. Reindl has received research support from The Neurological Research Laboratory (Markus Reindl, Medical University of Innsbruck and Tirol Kliniken) receives payments for antibody assays (AQP4- and anti-neuronal antibodies) and for AQP4- and MOG-antibody validation experiments organized by Euroimmu. Dr. Levy has nothing to disclose. Dr. Jarius has nothing to disclose. Dr. Tenembaum has nothing to disclose. Dr. Paul has nothing to disclose. Dr. Pittock has nothing to disclose. Dr. Marignier has nothing to disclose. Dr. Jacob has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Chugai, Sanofi-Genzyme and Terumo-BCT. Dr. Jacob has received research support from Biogen Adec, Alexion Pharmaceuticals.