Utilization, safety, and tolerability of ocrelizumab: Year 4 data from the Providence Ocrelizumab Registry

Introduction: Ocrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, was approved in the US in 2017 for the treatment of relapsing MS (RMS) and primary progressive MS (PPMS). The Providence OCR Registry (POR) was established to monitor long-term treatment and safety outcomes. Objective: To evaluate OCR treatment outcomes using real-world data from a diverse, community-based MS population. Methods: Adult MS patients who have been prescribed OCR were eligible. Chart reviews at OCR start date and every 6 months were done by a trained RN. Expanded Disability Status Scale (EDSS) scores were determined on the start date and then yearly. Descriptive statistics and paired t-tests were used. Results: Of the 437 patients enrolled from March 2017 to March 2021, 73.4% were female;mean age was 51.9 (±12.6) years;80.7% had RMS, 12.2% had SPMS, and 7.1% had PPMS. Median baseline EDSS [interquartile range (IQR)] was 3.0 [2.0, 4.0], 6.5 [6.0, 7.5], and 6.5 [6.0, 7.0] respectively. The RMS cohort had an annualized relapse rate (ARR) of 0.33 prior to starting OCR. Among all patients who had > 1 dose of OCR (n=407), ARR was 0.07. Median EDSS scores at 12 months were 3.0 [2.0, 4.5] (n=184) for RMS patients, 6.5 [6.5, 7.5] (n=32) for SPMS, and 6.5 [5.6, 7.5] (n=16) for PPMS. Infusion reactions occurred in 33.2% of patients during dose one, becoming less frequent with subsequent doses. Respiratory infections occurred in 40.5% of patients followed by urinary tract infections (UTI) (36.6%). Eight patients developed SARS-CoV-2 with no reported hospitalizations or deaths. Of 50 patients hospitalized, 19 had multiple hospitalizations. Over half of the hospitalizations were due to infections, and 69% (n=27) were 55 years or older. Of the 93 patients (21.3%) patients who stopped OCR, 47 patients stopped due to side effects with recurrent infections being the main reason for stopping followed by fatigue/malaise. The median time to discontinuation was 19.6 [IQR: 9.5, 30.2] months. There have been 7 deaths. Ninety-three patients who had baseline and 12 month Modified Fatigue Inventory (MFIS) had significant improvement at 12 months (mean difference -3.6 (±13.9), (p=0.01). Conclusions: Our study showed that OCR was effective in controlling relapse and disability worsening and reported similar rates of infusion reactions compared to earlier phase III clinical trials. A small number of our patients have developed SARS-CoV-2 with no adverse outcomes.