Ocrelizumab 920mg/23ml solution for injection vials

Background: Widespread use of ocrelizumab, an anti-CD20 monoclonal antibody, for treating patients with multiple sclerosis (MS), has led to an increase in reported adverse events following real-world observation. Among these, drug-induced colitis is a rare, but severe side effect, prompting a recent FDA statement regarding this safety concern. Objectives: We analyzed a cohort of ocrelizumab treated patients in our MS center to evaluate the incidence of drug-induced colitis. Methods: We present a critical review of the available literature on diagnosis and management of anti-CD20 induced colitis and display a case series of 3 suspected patients in our cohort. Results: Two patients met the full criteria for ocrelizumab-induced colitis, while a third partially met the criteria. Following symptomatic treatment and discontinuation of ocrelizumab, the patients showed favorable outcomes. Conclusion: Ocrelizumab-induced colitis is a rare, but severe adverse event. Its incidence may be higher than expected, reaching 1,95% in our cohort of MS patients. Further reporting of such cases is essential to broaden our understanding of this side effect.

Abstract licence: CC BY

Background: Patients with multiple sclerosis (PwMS) have an increased risk of infections. Objectives: To characterize incidence, clinical characteristics, outcomes and risk factors of infections, and serious infections (SIs) in ocrelizumab (OCR)-treated PwMS. Design: analysis of pooled data from 6155 patients in 13 clinical trials. Methods: = 2092). Results: Over a median (max) treatment period of 3.7 (13.9) years, 420/6155 patients (6.8%) experienced 583 SIs, excluding coronavirus disease 2019. Incidence rates in relapsing multiple sclerosis (RMS; 1.50 per 100 patient years [95% confidence interval (CI): 1.34-1.68]) and progressive multiple sclerosis (PMS; 3.70 [95% CI: 3.27-4.17]) remained stable over this period. Lower respiratory tract, urinary tract, abdominal and gastrointestinal, and skin infections were the most commonly reported SIs. Most SIs (~90%) resolved, and treatment with OCR was continued in >80% of cases. The presence of 1 or ⩾2 comorbidities (rate ratio = 1.66, 2.73, respectively), recent relapse activity (2.06), and Expanded Disability Status Scale (EDSS) score ⩾6.0 (2.02) were significant risk factors for SIs in patients with RMS treated over a median (max) period of 8.3 (11.2) years. In patients with primary PMS treated over a median (max) period of 7.1 (11.8) years, an EDSS score ⩾6.0 was associated with the greatest risk of SIs, a 4-fold increase (rate ratio, 4.31), followed by abnormal immunoglobulin (Ig)M levels (1.89), the presence of ⩾2 comorbidities (1.80), and having overweight/obesity (1.46). Time on OCR and abnormal IgG levels were not significantly associated with an increased SI risk. Conclusion: Continuous long-term treatment with OCR is associated with a manageable infection risk profile. Optimal disease control and addressing modifiable risk factors may reduce the risk of infections.

Abstract licence: CC BY

BACKGROUND: Anti-CD20 monoclonal antibodies are now a common first-line treatment for multiple sclerosis (MS). Rituximab, ocrelizumab and ofatumumab have all been associated with a dose-dependent risk of hypogammaglobulinaemia, but its relevance in clinical practice remains uncertain. OBJECTIVES: To study infection rates over time in a real-world cohort of people treated with ocrelizumab for MS, and their relationship to serum immunoglobulin. DESIGN: Observational study of 152 people receiving ocrelizumab for MS followed for up to 5.6 years (mean 2.7 years). RESULTS: Mean (SD) annualized changes in immunoglobulins during ocrelizumab treatment were IgM - 0.22 g/L/year (0.4), IgG - 0.38 g/L/year (0.9), IgA - 0.03 g/L/year. Rates of self-reported infection increased significantly during the first 4 years of treatment. Infection rates were not only associated with total immunoglobulin levels but also independently associated with age, comorbidity and female sex. We demonstrated for the first time that 29 out of 34 (87%) people on ocrelizumab with IgG in the lower normal range had sub-protective antibody responses to pneumococcus / haemophilus influenzae. CONCLUSIONS: Real-world observational studies complement open label extensions of clinical trials, often by having a more representative cohort and more complete follow-up. Our data suggest that while serious infections are rare in people on ocrelizumab, non-serious infections become increasingly burdensome. We offer practical suggestions on mitigating the risk of infection on ocrelizumab and other anti-CD20 medications.

Abstract licence: CC BY