Subject terms
tissue damage, retinal degeneration, RRMS, PPMS, Confirmed disability, multiple sclerosis, neurological deficits, disability
SCLEROSIS, RETINAL DEGENERATION, DISEASE COURSE, DISEASE, LYSIS, CDA, MULTIPLE SCLEROSIS
Ocrelizumab is a B cell-depleting drug widely used in relapsing–remitting multiple sclerosis (RRMS) and primary-progressive MS. In RRMS, it is becoming increasingly apparent that accumulation of disability not only manifests as relapse-associated worsening (RAW) but also as progression independent of relapse activity (PIRA) throughout the disease course. This study’s objective was to investigate the role of PIRA in RRMS patients treated with ocrelizumab. We performed a single-center, retrospective, cross-sectional study of clinical data acquired at a German tertiary multiple sclerosis referral center from 2018 to 2022. All patients with RRMS treated with ocrelizumab for at least six months and complete datasets were analyzed. Confirmed disability accumulation (CDA) was defined as a ≥ 12-week confirmed increase from the previous expanded disability status scale (EDSS) score of ≥ 1.0 if the previous EDSS was ≤  5.5 or a ≥ 0.5-point increase if the previous EDSS was > 5.5. PIRA was defined as CDA without relapse since the last EDSS measurement and at least for the preceding 12 weeks. RAW was defined as CDA in an interval of EDSS measurements with ≥ 1 relapses. Cox proportional hazard models were used to analyze the probability of developing PIRA depending on various factors, including disease duration, previous disease-modifying treatments (DMTs), and optical coherence tomography-assessed retinal degeneration parameters. 97 patients were included in the analysis. Mean follow-up time was 29 months (range 6 to 51 months). 23.5% developed CDA under ocrelizumab therapy (n = 23). Of those, the majority developed PIRA (87.0% of CDA, n = 20) rather than RAW (13.0% of CDA, n = 3). An exploratory investigation using Cox proportional hazards ratios revealed two possible factors associated with an increased probability of developing PIRA: a shorter disease duration prior to ocrelizumab (Open Access funding enabled and organized by Projekt DEAL.Multiple sclerosis (MS) is a disease of the central nervous system in which inflammation-associated tissue damage translates into neurological deficits of the patients. Classically, the disease is categorized as Ocrelizumab is a potent immunotherapy used for treatment of PPMS and RRMS. The monoclonal antibody directed against the CD20 molecule leads to lysis and depletion of B cells. In PPMS, it remains the only approved disease-modifying treatment option to this day. In RRMS, it is most commonly used as second-line therapy when first-line treatment options turn out to be insufficiently effective. However, in highly-active disease, it is also used as first-line medication. Using data from the pivotal phase 3 randomized controlled trials (RCTs) OPERA I and OPERA IIData from RCTs remain the indispensable golden standard for proving the efficacy and safety of new drugs. Some of RCTs' most significant strengths, i.e. homogeneity of the population, tight control of per-protocol application of the drug, very close clinical follow-up, can sometimes also be a disadvantage when the study conditions do not reflect real world clinical setting well. Therefore, complementary to RCT data, so-called real-world data play an increasing role in clinicians' decision-making in general