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Objective:To compare the clinical effectiveness of high- and low-efficacy treatments in patients with recently active and inactive secondary progressive multiple sclerosis (SPMS) after accounting for therapeutic lag.Methods:Patients treated with high- (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferon β, glatiramer acetate, teriflunomide) therapies after SPMS onset were selected from MSBase and OFSEP, two large observational cohorts. Therapeutic lag was estimated for each patient based on their demographic and clinical characteristics. Propensity score was used to match patients treated with high and low-efficacy therapies. Outcomes after disregarding the period of therapeutic lag were compared in paired, pairwise-censored analyses.Results:1000 patients were included in the primary analysis. Patients with active SPMS treated with high-efficacy therapy experienced less frequent relapses than those on low-efficacy therapy (hazard ratio [HR] 0.7, p=0.006). In patients with inactive SPMS, there was no evidence for a difference in relapse frequency between groups (HR=0.8,p=0.39). No evidence for a difference in the risk of disability progression was observed.Conclusion:In treated patients with SPMS, high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active, but not those with inactive, SPMS. However, more potent therapies do not offer an advantage in reducing disability progression in this patient group.Classification of Evidence:This study provides class III evidence that high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active SPMS whilst we did not find a difference in disability progression between patients treated with high- and low-efficacy therapy.

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Background Multiple sclerosis is an inflammatory and neurodegenerative disease. People with multiple sclerosis (pwMS) experience chronic fatigue which is difficult to deal with therapeutically and greatly affects health-related quality of life (QOL). PwMS are aware of the lack of generalized dietary advice related to their disease, leading to self-experimentation with diet. It is necessary to provide objective information about dietary interventions for pwMS. We aim to provide an objective synthesis of the evidence for efficacy and safety of specific diets in pwMS through a rapid review and meta-analyses of randomized controlled trials (RCTs), examining symptomatic fatigue (MFIS), QOL, Expanded-Disability-Status-Scale (EDSS), and severe adverse events. Methods We have carried out a rapid review (MEDLINE and EMBASE) up to December 2021, with PRISMA methodology, and meta-analyses, of (RCTs). All statistical analyses were performed using the comprehensive meta-analysis (CMA) -RStudio 4.1.3. The analysis used weighted mean differences (WMD) and a 95% confidence interval (CI) using a random-effects model to compare the effects of the dietary intervention with the control. Results Eight studies met the inclusion criteria. Of these eight studies, five analyzed EDSS, three MFIS, and three QOL. A total of 515 patients were analyzed. These meta-analyses cumulative evidence support that dietary intervention is associated with a trend of reduction in fatigue (308 patients studied) -the difference between means (SMD) of the control group and intervention group was -2,033, 95%-IC (-3,195, -0,152), a p-value of 0.0341)-, an increase in QOL (77 patients studied), no significant effect on EDSS (337 patients studied), and no severe adverse events. Conclusions It is difficult to reach a high level of evidence in dietary studies. Our findings show that dietary intervention is associated with a trend of reduction in fatigue in MS. Taking into account the potential of dietary interventions and the benefit/risk ratio in their favor, neurologists must be aware of the great importance of making interventions on diet in MS if necessary. There are dietary interventions with some evidence of benefit for patients with MS, which could be chosen based on adherence, patient preferences, and individual outcomes. Large prospective clinical trials are needed to shed further light on this topic.