Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis.

Importance: Ocrelizumab, a humanized monoclonal antibody targeted against CD20+ B cells, reduces the frequency of relapses by 46% and disability worsening by 40% compared with interferon beta 1a in relapsing-remitting multiple sclerosis (MS). Rituximab, a chimeric monoclonal anti-CD20 agent, is often prescribed as an off-label alternative to ocrelizumab. Objective: To evaluate whether the effectiveness of rituximab is noninferior to ocrelizumab in relapsing-remitting MS. Design, Setting, and Participants: This was an observational cohort study conducted between January 2015 and March 2021. Patients were included in the treatment group for the duration of study therapy and were recruited from the MSBase registry and Danish MS Registry (DMSR). Included patients had a history of relapsing-remitting MS treated with ocrelizumab or rituximab, a minimum 6 months of follow-up, and sufficient data to calculate the propensity score. Patients with comparable baseline characteristics were 1:6 matched with propensity score on age, sex, MS duration, disability (Expanded Disability Status Scale), prior relapse rate, prior therapy, disease activity (relapses, disability accumulation, or both), magnetic resonance imaging lesion burden (missing values imputed), and country. Exposure: Treatment with ocrelizumab or rituximab after 2015. Main outcomes and Measures: Noninferiority comparison of annualized rate of relapses (ARRs), with a prespecified noninferiority margin of 1.63 rate ratio. Secondary end points were relapse and 6-month confirmed disability accumulation in pairwise-censored groups. Results: Of the 6027 patients with MS who were treated with ocrelizumab or rituximab, a total of 1613 (mean [SD] age; 42.0 [10.8] years; 1089 female [68%]) fulfilled the inclusion criteria and were included in the analysis (898 MSBase, 715 DMSR). A total of 710 patients treated with ocrelizumab (414 MSBase, 296 DMSR) were matched with 186 patients treated with rituximab (110 MSBase, 76 DMSR). Over a pairwise censored mean (SD) follow-up of 1.4 (0.7) years, the ARR ratio was higher in patients treated with rituximab than in those treated with ocrelizumab (rate ratio, 1.8; 95% CI, 1.4-2.4; ARR, 0.20 vs 0.09; P < .001). The cumulative hazard of relapses was higher among patients treated with rituximab than those treated with ocrelizumab (hazard ratio, 2.1; 95% CI, 1.5-3.0). No difference in the risk of disability accumulation was observed between groups. Results were confirmed in sensitivity analyses. Conclusion: In this noninferiority comparative effectiveness observational cohort study, results did not show noninferiority of treatment with rituximab compared with ocrelizumab. As administered in everyday practice, rituximab was associated with a higher risk of relapses than ocrelizumab. The efficacy of rituximab and ocrelizumab administered at uniform doses and intervals is being further evaluated in randomized noninferiority clinical trials.

Focal segmental glomerulosclerosis in a patient with multiple sclerosis treated with Teriflunomide and Ocrelizumab.

We describe the case of a 24-year-old male patient with multiple sclerosis (MS) who was treated with Teriflunomide for eight months. However, due to MS progression, treatment was switched to Ocrelizumab. After 15 months of therapy with Ocrelizumab the patient developed edema and nephrotic-range albuminuria. Kidney biopsy showed focal segmental glomerulosclerosis (FSGS) and Ocrelizumab treatment was stopped. Teriflunomide is less likely to have caused FSGS due to a three week wash-out period and a timespan of 15 months between the last Teriflunomide dose and development of albuminuria. Treatment with Ocrelizumab has been associated with organ-specific inflammation in MS-patients, thus an association between the development of FSGS and Ocrelizumab therapy is possible, and this case suggests considering this potential association.

Initial high-efficacy disease-modifying therapy in multiple sclerosis: A nationwide cohort study.

OBJECTIVE: To determine the effectiveness of high-efficacy disease-modifying therapies (heDMTs) vs medium-efficacy disease-modifying therapies (meDMT) as the first treatment choice in treatment-naive patients with multiple sclerosis (MS) on disability worsening and relapses. We assessed this using a nationwide population-based MS registry. METHODS: We identified all patients starting a heDMT as first-time treatment from the Danish Multiple Sclerosis Registry and compared treatment outcomes with a propensity score matched sample of patients starting meDMT. RESULTS: We included 388 patients in the study: 194 starting initial therapy with heDMT matched to 194 patients starting meDMT. At 4 years of follow-up, the probabilities of a 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening were 16.7% (95% confidence interval [CI] 10.4%-23.0%) and 30.1% (95% CI 23.1%-37.1%) for heDMT and meDMT initiators, respectively (hazard ratio [HR] 0.53, 95% CI 0.33-0.83, p = 0.006). Patients initiating heDMT also had a lower probability of a first relapse (HR 0.50, 95% CI 0.37-0.67). Results were similar after pairwise censoring and in subgroups with high baseline activity, diagnosis after 2006, or information on baseline T2 lesion load. CONCLUSION: We found a lower probability of 6-month confirmed EDSS score worsening and lower probability of a first relapse in patients starting a heDMT as first therapy, compared to a matched sample starting meDMT. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with MS, starting heDMT lowers the risk of EDSS worsening and relapses compared to starting meDMT.

[Valproate can induce reversible encephalopathy]. / Valproat kan inducere reversibel encefalopati.

Valproate (VPA) is a widely used antiepileptic drug ­ also in the elderly. A female patient was diagnosed with epilepsy at the age 60 of years and treated with VPA for 16 years before developing tremor, rigidity, cognitive impairment and descending consciousness progressing to coma. After discontinuation of VPA she regained full consciousness, could talk and feed herself. The extrapyramidal and cognitive symptoms completely subsided during the following months. VPA-induced encephalopathy is an uncommon but serious adverse effect that should be considered in patients with cognitive decline during VPA treatment.

[Valproate can induce reversible encephalopathy].

Valproate (VPA) is a widely used antiepileptic drug - also in the elderly. A female patient was diagnosed with epilepsy at the age of 60 years and treated with VPA for 16 years before developing tremor, rigidity, cognitive impairment and descending consciousness progressing to coma. After discontinuation of VPA she regained full consciousness, could talk and feed herself. The extrapyramidal and cognitive symptoms completely subsided during the following months. VPA-induced encephalopathy is an uncommon but serious adverse effect that should be considered in patients with cognitive decline during VPA treatment.