Rituximab treatment of MS: a single centre retrospective observational study

Abstract

Abstract Degree Project thesis in Programme in Medicine, 2015 Rituximab treatment of MS: a single centre retrospective observational study F.Holm, M.Axelsson University of Gothenburg, Department of Clinical Neuroscience and Rehabilitation, Gothenburg, Sweden, 2015 Background Monoclonal antibodies targeting B-cells has become one of the most promising options in the treatment of autoimmune diseases. In multiple sclerosis (MS), rituximab (RTX) has been evaluated in two phase II studies. While RTX showed beneficial effects in relapsing-remitting (RR) MS, the study of primary progressive (PP) MS was negative. Yet, a subgroup analysis revealed lower rate of progression in younger patients with ≥1 contrast enhancing lesion on MRI (Magnetic Resonance Imaging). RTX is not approved for MS, but the off-label use has over recent years increased in Sweden and comprises 19,2% (May 2015) of all MS treatments. Objectives To evaluate the reason for use, efficacy, safety and tolerability of RTX treatment in MS. Method In this retrospective study we searched the Swedish MS register (SMSreg) and treatment registers for MS patients treated with RTX between 2008 to 2014. We identified 105 patients; 41 RRMS, 41 secondary progressive (SP) MS and 23 PPMS. Data were extracted from the SMSreg and medical chart review. RTX was initiated with 2 infusions of 1000 mg, 2 weeks apart, and then as single infusions at 6 months intervals. Results Reasons for switching to RTX varied from one to several combined causes. In RRMS patients (n=41) the reason was treatment failure on other disease modifying therapies (DMTs, 56%), JC virus antibody (JCV+) in natalizumab treated patients (34%), adverse events (AE) from previous DMT (Disease Modifying Treatment)(20%), and neutralizing antibodies (NAB) against interferon beta or nataluzimab (7%). The corresponding reasons for RTX in the PMS group (n=64, both SPMS and PPMS) was disease activity and progression (90%), JCV+ (12%), AE (6%) and NAB (3%). Comparing the number of patients having “relapses the last two years” and “relapses after RTX start” shows a reduction in both the RRMS patients (from 36.6% to 9.8%) and PMS patients (from 21.8% to 7.8%). RTX median treatment time was 13 (3-74) months. During RTX treatment of RRMS and PMS the median expanded disability status scale (EDSS) increased (+0.5, range 0-8.0 and +0.5, range 1.5-8.5, respectively), median multiple sclerosis severity scale (MSSS) decreased (-0.66, range 0.86-9.94 and -0.19, range 1.43-9.95, respectively). However the MSSS-score did not show statistical significance, p=0.077. Infusion related reactions was 49.5% at first infusion, 13.3% at 2nd infusion, and 9.5% at 3rd RTX infusion. No severe AE was recorded. 16 patients stopped RTX treatment; 6 due to AE, 4 due to treatment failure and 6 of unknown reasons. Conclusions RTX was used as treatment primarily as a last line of treatment after having disease activity in previous treatments. RTX was well tolerated with no severe AE. RTX had no obvious effect on EDSS progression but decreased relapse rate and MSSS which could indicate a beneficial effect in both RRMS and PMS.