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. Interim data analyses occur on a biannual basis and findings are reported yearly. This is the third iteration.
We sought to determine the frequency of serious infections and malignancy in a real-world population receiving OCR with characteristics outside the inclusion parameters of the phase II and III trials.
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.
As of interim analysis in December 2019, 291 subjects were enrolled, 181 subjects had reached 12 months of treatment, 131 subjects had reached 18 months, and 84 subjects had reached 24 months. Subjects were 29% male, 71% female, with an age range of 18-73. Sixty three percent had RRMS and 37% PMS (PPMS and progressive RRMS) with an EDSS range of 0–7.5; 25% had a baseline EDSS of ≥ 6.0 with a median of 3.0.
The rate of infections for all OCR-treated patients was 43% (6% bronchitis, 2% zoster, 56% URIs, 30% UTIs, 4% HSV, and 25% other infections). Four percent of subjects had a serious infection (one that required hospitalization, was felt to be life-threatening, or resulted in death). Three percent of subjects had clinical or MRI relapses. 8% of subjects had a history of prior neoplasm (excluding basal cell carcinoma). Two malignancies have occurred during OCR treatment.
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.