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: Post-hoc analysis of pooled data from 6155 patients in 13 clinical trials.
Methods: Descriptive analyses of clinical characteristics and outcomes were reported over ⩽14 years. A Poisson Generalized Estimating Equation model was constructed to examine risk factors in a subgroup of patients with longer exposure to OCR (n = 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.
Keywords: comorbidities; disease-modifying therapies; infections; long-term data; multiple sclerosis; safety; serious infections.
Is continued treatment with ocrelizumab associated with a higher risk of infections and serious infections in patients with multiple sclerosis? Patients with multiple sclerosis (PwMS) are at an increased risk of infections compared with the general population. Infections are also among the most frequently reported side effect in PwMS treated with ocrelizumab. Initial analyses have shown that serious infection (SI) rates in PwMS treated with ocrelizumab were stable over 6 years, but there is concern that this rate may increase with continued treatment. This study aimed to describe infections and SIs in PwMS treated with ocrelizumab and look into factors that increase patients’ susceptibility to infections. We analyzed the largest population of PwMS ever treated with ocrelizumab, including 6155 patients from 13 clinical trials. Some of these patients received ocrelizumab for as long as 14 years. Approximately 7 out of every 100 patients experienced SIs, excluding COVID-19 infections, with no increase in yearly rates of SIs over time. Pneumonia and urinary tract infections were the most common SIs. Almost all patients recovered from their infections (>9 out of 10 cases), and continued treatment with ocrelizumab (>8 out of 10 cases). When looking at factors that made PwMS more prone to SIs, we found that patients with relapsing MS had an increased risk if they had experienced recent MS relapses, severe walking difficulties, or other health conditions like diabetes and bladder problems. Patients with primary progressive MS (PPMS) with severe walking difficulties were four times more likely to have SIs. Having other health conditions like heart or bladder problems, low levels of immunoglobulin M, or excess weight also increased the risk of SIs in patients with PPMS. In conclusion, continued treatment with ocrelizumab did not increase the risk of SIs, and most of those infections resolved without stopping ocrelizumab treatment. Addressing certain health conditions and achieving a good control of the MS disease may help to reduce the risk of SIs.
© The Author(s), 2024.