Comparative effectiveness of autologous hematopoietic stem cell transplant vs fingolimod, natalizumab, and ocrelizumab in highly active relapsing-remitting multiple sclerosis

Importance: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). Objective: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. Design, Setting, and Participants: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. Exposure: AHSCT vs fingolimod, natalizumab, or ocrelizumab. Main outcomes: Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Results: Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). Conclusion: In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time

Long-term outcomes in patients presenting with optic neuritis: Analyses of the MSBase registry

Background: Short-term outcomes of optic neuritis (ON) have been well characterized. Limited data exists on longer-term visual outcomes in patients who present with ON. The large MSBase registry allows for characterization of long-term visual outcomes after ON. Methods: Via the MSBase Registry, data on patients from 41 centers was collected during routine clinical and research visits. Physical and visual disability were measured using the expanded disability status scale (EDSS) and the visual function score (VFS). Inclusion criteria for this analysis included age ≥ 18 years, clinically isolated syndrome (CIS), ON-onset, baseline visit within 6 months of onset, and at least one follow-up visit. Survival analysis was used to evaluate the association of disease-modifying treatment with time to conversion to clinically definite MS or sustained EDSS/VFS progression. Results: Data from 60,933 patients were obtained from the MSBase registry in July 2019. Of these, 1317 patients met inclusion criteria; 935 were treated at some point in disease course, while 382 were never treated. At baseline, mean age was 32.3 ± 8.8 years, 74% were female, median EDSS was 2 (IQR 1–2), and median VFS was 1 (IQR 0–2). Median follow-up time was 5.2 years (IQR 2.4–9.3). Treatment was associated with reduced risk and delayed conversion to clinically definite MS (HR = 0.70, p < 0.001), sustained EDSS progression (HR = 0.46, p < 0.0001) and sustained VFS (HR = 0.41, p < 0.001) progression. Conclusions: In the MSBase cohort, treatment after ON was associated with better visual and neurological outcomes compared to no treatment. These results support early treatment for patients presenting with ON as the first manifestation of MS

Examining cross-sectional relationships of optical coherence tomography, cervical cord MRI and disability in secondary progressive MS

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