Escalating to medium- versus high-efficacy disease modifying therapy after low-efficacy treatment in relapsing remitting multiple sclerosis.

BACKGROUND: In patients with relapsing remitting multiple sclerosis (RRMS) on low-efficacy disease modifying therapies (DMT), the optimal strategy on how to escalate treatment once needed, remains unknown. METHODS: We studied RRMS patients on low-efficacy DMTs listed in the Swiss National Treatment Registry, who underwent escalation to either medium- or high-efficacy DMTs. Propensity score-based matching was applied using 12 clinically relevant variables. Both groups were also separately matched with control subjects who did not escalate therapy. Time to relapse and to disability worsening were evaluated using Cox proportional hazard models. RESULTS: Of 1037 eligible patients, we 1:1 matched 450 MS patients who switched from low-efficacy to medium-efficacy (n = 225; 76.0% females, aged 42.4 ± 9.9 years [mean ± SD], median EDSS 3.0 [IQR 2-4]) or high-efficacy DMTs (n = 225; 72.4% females, aged 42.2 ± 10.6 years, median EDSS 3.0 [IQR 2-4]). Escalation to high-efficacy DMTs was associated with lower hazards of relapses than medium-efficacy DMTs (HR = 0.67, 95% CI 0.47-0.95, p = .027) or control subjects (HR = 0.61, 95% CI 0.44-0.84, p = .003). By contrast, escalation from low to medium-efficacy DMTs did not alter the hazard for relapses when compared to controls (i.e. patients on low-efficacy DMT who did not escalate DMT during follow-up) CONCLUSION: Our nationwide registry analysis suggests that, once escalation from a low-efficacy DMT is indicated, switching directly to a high-efficacy treatment is superior to a stepwise escalation starting with a moderate-efficacy treatment.

Anti-CD20 immunotherapy in progressive multiple sclerosis: 2-year real-world follow-up of 108 patients.

BACKGROUND: Anti-CD20 monoclonal antibodies are recently introduced treatments in progressive MS and real-world data are lacking. OBJECTIVE: The aim of this study is to describe a cohort of progressive MS patients treated with ocrelizumab or rituximab in a real-world setting. METHODS: This monocentric prospective cohort study at the University Hospital of Strasbourg included patients with primary progressive or secondary progressive MS that started treatment with anti-CD20 antibodies before June 2019. Every six months, patients were assessed using the following standardized clinical evaluations: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9-HPT) and Symbol Digit Modalities Test (SDMT). The primary analysis considered EDSS progression (of at least 1.0 if EDSS ≤ 5.5 and at least 0.5 if EDSS ≥ 6.0). RESULTS: We included 108 patients, with a median age upon inclusion of 53 years [48.0-58.0]. 72% were classified as primary progressive forms. Median baseline EDSS was 6.0 [4.0-6.5]. EDSS was significantly correlated with T25FW, SDMT and 9-HPT. Following 2 years of treatment, 38.9% of patients presented EDSS progression compared to baseline. CONCLUSION: Our large cohort confirms tolerance of these treatments in a real-world setting. Standardized clinical assessments could improve detection of deteriorating patients. Further studies are needed to establish predictive factors.

A rise in cases of nitrous oxide abuse: neurological complications and biological findings.

BACKGROUND: The recent lockdown due to the COVID-19 pandemic has been linked to a higher incidence of psychiatric manifestations and substance abuse. The recreative use of nitrous oxide is more and more widespread and neurological complications are frequent. METHODS: We report clinical characteristics and biological findings of five consecutive patients presenting to our tertiary care center between April 2020 and February 2021 with various neurological symptoms occurring after recent nitrous oxide abuse. RESULTS: Our patients presented with subacute combined degeneration of the spinal cord (4/5 patients) or with acute inflammatory demyelinating polyneuropathy (1/5 patients). No patient had reduced vitamin B-12 titer, but all had elevated blood levels of homocysteine and methylmalonic acid. This reflects the functional deficit in vitamin B-12 that can be linked to nitrous oxide consumption. After vitamin B-12 supplementation, clinical signs regressed at least partially in all 5 patients. CONCLUSION: We report an elevated incidence of neurological complications of nitrous oxide abuse occurring during the recent COVID-19 lockdown. Nitrous oxide abuse should be tracked down in patients presenting with compatible neurological symptoms and elevated homocysteinemia. Vitamin B-12 should be supplemented as soon as the diagnosis is made.