Acapella: Real-World Experience with Ocrelizumab: An Observational Study Evaluating Safety in Patients with Relapsing and Progressive MS, Year Five Data

Background: Ocrelizumab (OCR) is a humanized, monoclonal antibody targeting CD20+ B cells and is approved for treatment of relapsing remitting (RRMS) and primary progressive MS (PPMS). The ACAPELLA trial is a prospective study with a primary objective of assessing OCR-associated adverse events (AEs) in a real-world MS population. ACAPELLA includes patients with preexisting conditions exempted from the phase II & III clinical trials, such as a prior history of malignancy, prior immunosuppressive treatment, and more advanced age and/or disability.

Objectives: We sought to describe the occurrence of serious infections and malignancies in a real-world population receiving OCR, including those with characteristics outside the inclusion parameters of the phase II and III trials.

Methods: The study includes all subjects treated with OCR at the Elliot Lewis Center since its commercial release in March 2017. Initial assessments include EDSS, brain MRI, mammograms (standard of care), collection of medical history including prior serious or recurrent infections, history of malignancy and exposure to immunosuppressive treatment, JCV index, and CD19 count.

Results: As of December 31, 2021, 365 subjects were actively enrolled, 322 subjects completed 2 cycles of OCR, 285 subjects completed 3 cycles, 246 subjects completed 4 cycles, 206 subjects completed 5 cycles, 160 subjects completed 6 cycles, 123 patients completed 7 cycles, 82 subjects completed 8 cycles, 41 subjects completed 9 cycles, and 8 subjects completed 10 cycles. The patient population was 28% male, 72% female, with an age range of 18-73. Sixty-six percent had RRMS and 34% PMS (PPMS and SPMS) with an EDSS range of 0–7.5; ­­­­22% had a baseline EDSS of ≥ 6.0 with a median of 3.0.

In the five years of our study, 14 patients had a serious infection not related to COVID-19. Serious infection is defined as requiring hospitalization. Twelve subjects had clinical or MRI relapses during this 5-year period; 25 subjects had a history of prior neoplasm (excluding basal cell carcinoma). Six new malignancies occurred during OCR treatment. Forty- nine subjects were diagnosed with COVID-19 infection, and 6 required hospitalization.

Conclusions: Thus far, the incidence of AEs is comparable to that seen in the phase III trials and in previously reported ACAPELLA data. Additional topics of interest in the ACAPELLA population include the effect of continued OCR dosing on JCV index values and immunoglobulin levels, and changes in EDSS and MRI over time.