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A critical issue in the management of relapsing MS (RMS) is the discontinuation of disease-modifying treatments (DMT) due to lack of efficacy, intolerability or impending risks. With new therapeutic agents introduced into the treatment of RMS, immediate- and long-term consequences of sequential drug use, as well as the effect of the sequence in which the drugs are given, are unclear but may affect efficacy, adverse events, and long-term immunocompetence. In the absence of clinical studies specifically addressing these concerns, observations from clinical practice are of particular value in guiding current management algorithms. Prompted by a study published by Ferraro et al. in this journal, we set out to provide an overview of the published real-world evidence on the effectiveness and safety of switching from fingolimod to another DMT in patients with active RMS. Seventeen publications reporting relevant information were identified. The literature suggests that immune cell depletion induced by alemtuzumab or ocrelizumab is associated with an increased risk of relapse and worsening disability in patients switching from fingolimod compared to patients switching from other therapeutic agents. However, the evidence reported for natalizumab and cladribine is inconclusive. While shortening of the washout period may limit early disease reactivation after fingolimod discontinuation, there is no strong evidence that the duration of the washout period or the absolute lymphocyte count at baseline are predictors of attenuated long-term efficacy. Further real-world studies are required to better understand outcomes among patients who are under-represented in controlled trials. [ABSTRACT FROM AUTHOR]

Objective: Progressive multifocal leukoencephalopathy (PML) is a serious viral infection associated with disease-modifying therapies (DMT) for multiple sclerosis (MS) including sphingosine 1-phosphate receptor (S1PR) modulators. The objective of this review was to investigate the characteristics of PML in MS patients associated with drugs of the S1PR modulator. Methods: We conducted a literature review and analysis of 24 patients from 12 publications in PubMed, SCOPUS and EMBASE. This is a descriptive analysis and study of characteristics of PML associated fingolimod and related S1PR modulator group of DMT. Results: A total of 24 cases of PML in MS patients treated with fingolimod were identified. Of these, 21 cases contained data regarding changes in the expanded disability status scale (EDSS). One case of PML in association with ozanimod treatment in a clinical trial was also identified. In PML cases associated with fingolimod, the mean age at the time of PML diagnosis was 50.91 ± 11.5 years. All patients were treated with fingolimod for more than 24 months. Compared to patients who improved or were stable, in terms of EDSS, after symptomatic management of PML, the non-improved groups were significantly older. There were no fatalities in either group during the reported follow-up period. Conclusion: The incidence of PML appears to be extremely low in MS patients treated with S1PR modulators. Risk of PML increases with increase in duration of treatment with S1PR modulators like fingolimod, and increased age at the time of PML diagnosis is associated with worse prognosis. [ABSTRACT FROM AUTHOR]

Background: Nonadherence to disease-modifying drugs (DMDs) for multiple sclerosis (MS) is associated with poorer clinical outcomes, including higher rates of relapse and disease progression, and higher medical resource use. A systematic review and quantification of adherence and persistence with oral DMDs would help clarify the extent of nonadherence and nonpersistence in patients with MS to help prescribers make informed treatment plans and optimize patient care. The objectives were to: 1) conduct a systematic literature review to assess the availability and variability of oral DMD adherence and/or persistence rates across 'real-world' data sources; and 2) conduct meta-analyses of the rates of adherence and persistence for once- and twice-daily oral DMDs in patients with MS using real-world data. Methods: A systematic review of studies published between January 2010 and April 2018 in the PubMed database was performed. Only studies assessing once- and twice-daily oral DMDs were available for inclusion in the analysis. Study quality was evaluated using a modified version of the Newcastle-Ottawa Scale, a tool for assessing quality of observational studies. The random effects model evaluated pooled summary estimates of nonadherence. Results: From 510 abstracts, 31 studies comprising 16,398 patients with MS treated with daily oral DMDs were included. Overall 1-year mean medication possession ratio (MPR; n = 4 studies) was 83.3% (95% confidence interval [CI] 74.5–92.1%) and proportion of days covered (PDC; n = 4 studies) was 76.5% (95% CI 72.0–81.1%). Pooled 1-year MPR ≥80% adherence (n = 6) was 78.5% (95% CI 63.5–88.5%) and PDC ≥80% (n = 5 studies) was 71.8% (95% CI 59.1–81.9%). Pooled 1-year discontinuation (n = 20) was 25.4% (95% CI 21.6–29.7%). Conclusions: Approximately one in five patients with MS do not adhere to, and one in four discontinue, daily oral DMDs before 1 year. Opportunities to improve adherence and ultimately patient outcomes, such as patient education, medication support/reminders, simplified dosing regimens, and reducing administration or monitoring requirements, remain. Implementation of efforts to improve adherence are essential to improving care of patients with MS. [ABSTRACT FROM AUTHOR]