Anti-CD20 monoclonal antibodies(BASF Corp.)

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.

To study infection rates over time in a real-world cohort of people treated with ocrelizumab for MS, and their relationship to serum immunoglobulin.

Observational study of 152 people receiving ocrelizumab for MS followed for up to 5.6 years (mean 2.7 years).

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.

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.

Anti-Jo-1 antisynthetase syndrome (Jo1⁺ASyS) is the most common form of idiopathic inflammatory myopathy with high relapse rates and limited treatment options beyond csDMARDs, which frequently fail to achieve adequate disease control. This study aimed to evaluate the efficacy and safety of anti-CD20 monoclonal antibodies (CD20mAbs) compared to conventional synthetic(cs) DMARDs in patients with Jo1⁺ASyS.

A single-center retrospective cohort of patients with Jo1⁺ASyS were collected at RenJi Hospital in China (2007-2023). A prevalent new-user design with time-based propensity scores, applied without replacement, was used to match CD20mAb and csDMARD users. The primary outcome was the percentage of patients reaching Low Disease Activity (5-item LDA), as defined by the absence of active arthritis, myositis, ILD, fever, and prednisone dosage ≤7.5 mg/day.

A total of 166 eligible treatment regimens, including CD20mAbs and csDMARDs, were extracted from 128 Jo1⁺ASyS patients with a median follow-up period of 5 years. Utilizing propensity score, 49 pairs of individual prescriptions for CD20mAbs and csDMARDs users were matched. The group treated with CD20mAbs exhibited a significantly higher rate of achieving LDA compared to those treated with csDMARDs (46.9 % vs. 22.4 %, p = 0.011). No significant differences in exposure-adjusted incidence rate were detected between the two treatment modalities (CD20mAbs vs. csDMARDs = 7.911 vs. 6.479 per 100 patient-yr, RR = 1.22; 95 % CI: 0.64, 2.36), with respect to major infections. Sensitivity analyses further confirmed the robustness of the superior effectiveness of the CD20mAbs compared to the csDMARDs.

CD20mAbs exhibited remarkable treatment efficacy and acceptable safety in patients with Jo1⁺ASyS. Cumulative evidence, including ours suggested that CD20mAbs should be considered as a first-line option for Jo1⁺ASyS.