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

Treatment adherence in multiple sclerosis: a survey of Belgian neurologists

Danny Decoo,1 Mathieu Vokaer2 1Department of Neurology and Neurorehab, AZ Alma, Sijsele, Belgium; 2Multiple Sclerosis Clinic, Edith Cavell Hospital, CHIREC group, Brussels, Belgium Background: Poor treatment adherence is common among patients with multiple sclerosis (MS). This survey evaluated neurologists’ perception of treatment adherence among MS patients.Materials and methods: This questionnaire-based survey of Belgian neurologists treating MS patients was conducted between June and July 2014. Face-to-face interviews with the neurologists were based on a semistructured questionnaire containing questions regarding the perception of the treatment-adherence level.Results: A total of 41 neurologists participated in the survey. Of these, 88% indicated frequent discussions about treatment adherence as beneficial for treatment efficacy. The mean time spent on the treatment-adherence discussion during the initial consultation was 11 minutes, with 24% of doctors spending 5 minutes and 24% of doctors spending 10 minutes discussing this issue. The majority of neurologists (56%) perceived the adherence level in MS as good, and 12% perceived it as excellent. The majority of neurologists (64%) indicated intolerance as a main cause of poor adherence, and all neurologists reported insufficient efficacy as a consequence of nonadherence. The importance of adherence in the neurologists’ practice was evaluated on a scale of 1–10, with 1= “not very important” and 10= “very important”: 44% of doctors indicated a score of 10, and the mean score was 9.0.Conclusion: Belgian neurologists consider treatment adherence in MS as essential for the benefits of therapies. However, although neurologists are aware of the consequences of nonadherence, they generally spend limited time discussing the importance of treatment adherence with their patients. Keywords: multiple sclerosis, treatment adherence, physician surve

Amiodarone: neurologische afwijkingen.

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Co-registration of PET and MRI in different courses of MS using cobalt-55 as a calcium-tracer.

Multiple Sclerosis (MS) is an auto-immune central nervous system (CNS) inflammation. At this moment, MRI is the most accurate paraclinical test in MS to monitor disease activity, although poorly correlated with clinical impairment. PET using Co-55 as a Ca-tracer may visualize Co-transport across the neuronal membrane, Ca-mediated inflammatory processes and passive leakage through a breach in the blood-brain barrier. Co-registration of MRI and Co-PET may actually allow identification of clinically active lesions. MRI and Co-PET were performed as described elsewhere. Based on a statistic parametric mapping (Spume)-software package, MRI and Co-PET were superimposed. A semi-automated technique was used to count the MS-lesions. We included four groups of eight MS-patients with relapsing-remitting (RR), primary progressive (PP), progressive relapsing (PR) and secondary progressive (SP) courses and with healthy volunteers. MS was assessed in terms of impairment using Kurtzke's Expanded Disability Status Scale (EDSS) and Scripps Neurological Rating Scale (NRS). Co-PET displayed focal uptake throughout the MS brain, both in the grey and white matter. All four patients groups (as compared to controls) demonstrated a more inhomogeneous distribution of Co-spots with a tendency to show clustering, most evident in RR-MS. SPM-analysis revealed an essentially different distribution pattern of MS spots on MRI and Co-PET. (Merging of) Co-PET and MRI may eventually form complementary tools for identifying clinically relevant lesions, thus providing a more reliable secondary outcome measure in MS