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Judicious multiple sclerosis (MS) diagnosis and early start of disease modifying therapy significantly improves long-term disability outcomes in persons with MS (pwMS). Retrospective analysis based on 25-year New York State MS Consortium (NYSMSC) data determined the effect of changes in the respective diagnostic criteria in shortening the time between symptom onset to MS diagnosis. Based on 9378 current and historical MS cases, there was a significant decrease in time to diagnosis in pwMS from 1982–2001 to >2017 periods (average 4.2 vs. 1.1 years, p < 0.001). Additional improvements and better implementation of the MS diagnostic criteria can further decrease the diagnosis lag. [ABSTRACT FROM AUTHOR]

Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study of patients with relapsing-remitting multiple sclerosis, treatment with cladribine tablets 3.5 mg/kg (CladT) significantly reduced the annualised relapse rate (ARR) versus placebo; this effect was sustained in CLARITY Extension, without further treatment. Objective: To assess the frequency and severity of relapses in patients treated with CladT versus placebo in CLARITY over 2 years and evaluate the durability of effect in patients who received no further treatment for 2 years in CLARITY Extension. Methods: In this post hoc analysis, ARRs were calculated for qualifying and all relapses, and qualifying and all severe relapses (i.e. requiring steroid treatment or leading to hospitalisation) in patients treated with CladT (n = 433) and placebo (n = 437) in CLARITY, and those from the CladT group who received placebo in CLARITY Extension (n = 98). Results: At Month 6, Year 1 and Year 2, patients receiving CladT had a significantly lower risk of qualifying or all relapses (all p < 0.0001), and qualifying or all severe relapses (all p < 0.005), compared with placebo. This effect was sustained in CLARITY Extension without further treatment. Conclusion: The results show durable efficacy of cladribine tablets 3.5 mg/kg for reducing frequency and severity of relapses in patients with relapsing-remitting multiple sclerosis. CLARITY: NCT00213135; CLARITY Extension: NCT00641537 [ABSTRACT FROM AUTHOR]

DMTs should be trialed in individuals with PPMS and SPMS with or without recent disease activity - Yes There is only one approved DMT for primary progressive (PP) MS, ocrelizumab.[1] There is a single modern era-positive phase-III trial in secondary progressive (SP) MS, with siponimod.[2] Many DMTs are approved by the Food and Drug Administration (FDA) for active SPMS, which they declared to be a form of relapsing MS. Multiple sclerosis (MS) is the poster child for success in Neurology, with multiple disease-modifying therapies (DMTs) developed to treat relapsing forms of MS. [Extracted from the article]

Background: In the Phase 3, 96-week ORACLE-MS study, cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dosage over two years) significantly reduced lesions associated with multiple sclerosis versus placebo in participants following a first clinical demyelinating event (FCDE). Objective: To determine the timing of effects of cladribine tablets on lesion activity assessed by magnetic resonance imaging (MRI). Methods: This post hoc analysis assessed the effect of cladribine tablets versus placebo in ORACLE-MS on secondary MRI endpoints including T1 gadolinium-enhancing (Gd+), new or enlarging T2 lesions, and combined unique active lesions assessed on MRI scans performed at screening and every 3 months thereafter. Results: Compared to placebo, cladribine tablets 3.5 mg/kg treatment appeared to lead to a trend of reductions in the mean number of T1 Gd+ lesions by Week 13 (first post-baseline scan: 0.37 vs. 1.00), new or enlarging T2 (0.20 vs. 1.01) and combined unique active (0.29 vs. 1.91) lesions by Week 24. Low lesion counts were maintained with cladribine tablets throughout 96weeks. Similar results were observed with the 5.25 mg/kg dosage. Conclusion: In participants with an FCDE, cladribine tablets appeared to reduce lesion numbers within 13 weeks (time of first evaluation). [ABSTRACT FROM AUTHOR]

Background: Teriflunomide is contraindicated in pregnancy. Some pregnancies have occurred despite guidance to use effective contraception. Objectives: To report outcomes of pregnancies occurring in teriflunomide clinical trials and the post-marketing setting. Methods: Outcomes are summarized for pregnancies in teriflunomide monotherapy clinical trials and the post-marketing setting (data cutoff: December 2017). Results: Of 437 confirmed teriflunomide-exposed pregnancies, 222 had known outcomes (70 from clinical trials; 152 from the post-marketing setting); 161 were reported prospectively and 61 retrospectively. There were 107 (48.2%) live births, 63 (28.4%) elective abortions, 47 (21.2%) spontaneous abortions, 3 (1.4%) ectopic pregnancies, 1 (0.5%) stillbirth, and 1 (0.5%) maternal death leading to fetal death. Four birth defects were reported among cases with known pregnancy outcome: ureteropyeloectasia (only defect considered major); congenital hydrocephalus; ventricular septal defect; and malformation of right foot valgus. A case of cystic hygroma was identified on antenatal ultrasound (pregnancy outcome unknown). One elective abortion followed prenatal diagnosis of fetal anomaly (blighted ovum). The risk of major birth defects in prospectively reported live birth/stillbirth outcomes was 3.6% (1/28) in clinical trials and 0.0% (0/51) in post-marketing reports. Conclusions: Outcomes were consistent with the general population. Current human data do not indicate a teratogenic signal in teriflunomide-exposed pregnancies. [ABSTRACT FROM AUTHOR]

Background: Fatigue is one of the most common and distressing symptoms among persons with multiple sclerosis (pwMS). Objective: The aim of this study is to evaluate fatigue as a predictor for disease worsening among pwMS. Methods: In this retrospective cohort study of New York State MS Consortium (NYSMSC) registry, MS patients reporting moderate-to-severe fatigue at study enrollment (n = 2714) were frequency matched to less-fatigued subjects (n = 2714) on age, baseline Kurtzke Expanded Disability Status Scale (EDSS), disease duration, and MS phenotype. Change from baseline patient-reported outcomes (PROs), as measured by LIFEware™, categorized participants into two groups: those with stable/improved outcomes and those who worsened. In a subgroup of patients with longitudinal data (n = 1951), sustained EDSS worsening was analyzed using Cox proportional hazards modeling to explore the effect of fatigue. Results: The median survival time from study enrollment to sustained EDSS worsening was 8.7 years (CI: 7.2–10.1). Participants who reported fatigue at baseline were more likely to experience sustained EDSS worsening during follow-up (HR: 1.4, 95% CI: 1.2–1.7). Patients who were fatigued at baseline were also more likely to report worsening psychosocial limitations (all p s ⩽ 0.01). Conclusion: In addition to being a common symptom of MS, severe fatigue was a significant predictor for EDSS worsening in the NYSMSC. [ABSTRACT FROM AUTHOR]

Background: The Treatment Satisfaction Questionnaire for Medication (TSQM) was designed to assess patient treatment satisfaction in chronic diseases. Its performance has not been examined in multiple sclerosis (MS). The 14 items of the TSQM cover four domains: Effectiveness, Side Effects, Convenience, and Global Satisfaction. Objective: To evaluate performance of the TSQM in patients with relapsing MS, using data collected from the TENERE study (NCT00883337), in which 324 patients received oral teriflunomide or subcutaneous interferon beta-1a for ≥48 weeks. Methods: Five measurement properties were examined using traditional psychometric methods: data completeness, scale-to-sample targeting, scaling assumptions, reliability (including test-retest), and construct validity (internal: item-level scaling success, confirmatory factor analysis, and exploratory factor analysis; external: convergence, discrimination, and group differences). Results: There were few (<2%) missing item data; domain scores could be computed for all patients. Score distributions were skewed toward higher satisfaction; two domains had marked ceiling effects. Scaling assumptions were supported. Internal consistency reliability was high (Cronbach's α > 0.90). Internal validity tests supported item groupings. Correlations supported convergent and discriminant construct validity; hypothesis testing supported group differences validity. Conclusion: This investigation found the TSQM to be a useful tool, exhibiting good psychometric measurement properties in patients with relapsing MS in the TENERE study. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a major acquired neurologic disease of young adults. The prototypic patient is a young woman of reproductive age. Gender preference is becoming more pronounced, since MS is increasing specifically among women. Any healthcare provider who deals with MS must be prepared to discuss pregnancy issues, and provide appropriate counseling. This is now complicated by the availability of multiple treatment options. There is growing literature on which to base recommendations, particularly regarding washout periods. After a brief background introduction, this review will discuss state-of-the-art family planning counseling in the treatment era, divided into prepregnancy, pregnancy, and postpartum MS issues. [ABSTRACT FROM AUTHOR]

Healthy control participants (46 women, M age 44.3 yr., SD= 7.6; 29 men) were recruited to undergo a comprehensive neuropsychological battery and serve as a comparison group in a study of cognitive functioning in patients with Lyme disease. Participants were selected using Mitofsky-Waksberg random digit dialing. The Buschke 12-word, six-trial Selective Reminding Test was administered as part of the neuropsychological battery and normative data are presented stratified by age and sex. Performance on alternate forms of this measure were examined. Mean education, intelligence quotient, and Wide Range Achievement Test-3 Reading scores are reported. [ABSTRACT FROM AUTHOR]