Adherence to subcutaneous interferon beta-1a treatment using an electronic injection device:a prospective open-label Scandinavian noninterventional study (the ScanSmart study)

Background: Disease modifying drugs help control the course of relapsing remitting multiple sclerosis (RRMS); however, good adherence is needed for long-term outcomes. Objective: To evaluate patient adherence to treatment with subcutaneous interferon beta-1a using RebiSmart® and assess injection-site reactions and treatment satisfaction. Methods: This prospective, single-arm, open-label, noninterventional multicenter Phase IV trial included disease modifying drug-experienced mobile patients with RRMS. Adherence was measured over 12 weeks. Items 13–23, 35, 37, and 38 of the Multiple Sclerosis Treatment Concerns Questionnaire (injection-site reactions and treatment satisfaction) were recorded at 12 weeks. Results: Sixty patients were recruited (mean age 43.7 [±SD 7.9] years; 83% female; mean years since multiple sclerosis diagnosis 6.7 [SD 4.5]). Adherence data were obtained in 54 patients only due to technical problems with six devices. Over 12 weeks, 89% (n=48) of patients had ≥90% adherence to treatment. Most patients experienced mild influenza-like symptoms and injection-site reactions, and global side effects were minimal. Most patients (78%) rated the convenience as the most important aspect of the device, and most experienced no or mild pain. Conclusion: RRMS patients treated with subcutaneous interferon beta-1a, administered with RebiSmart, demonstrated generally good adherence, and the treatment was generally well tolerated

A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis - An explorative study

OBJECTIVE: To compare baseline physical and cognitive performance, neurophysiological, and magnetic resonance imaging (MRI) outcomes and examinetheir interrelationship inparticipants with Multiple Sclerosis (MS), already established aseither responder or non-responder to Fampridine treatment, andto examine associationswiththe expanded disability status scale (EDSS) and 12-item MS walking scale (MSWS-12). METHODS: Baseline data from an explorative longitudinal observational study were analyzed. Participants underwent the Timed 25-Foot Walk Test (T25FW), Six Spot Step Test (SSST), Nine-Hole Peg Test, Five Times Sit-to-Stand Test, Symbol Digit Modalities Test (SDMT), neurophysiological testing, including central motor conduction time (CMCT), peripheral motor conduction time (PMCT), motor evoked potential (MEP) amplitudesand electroneuronographyof the lower extremities, and brain MRI (brain volume, number and volume of T2-weighted lesions and lesion load normalized to brain volume). RESULTS: 41 responders and 8 non-responders were examined. There were no intergroup differences inphysical performance, cognitive, neurophysiological, andMRI outcomes (p > 0.05).CMCT was associated withT25FW, SSST, EDSS, and MSWS-12,(p < 0.05). SDMT was associated with the number and volume of T2-weighted lesions, and lesion load normalized to brain volume (p < 0.05). CONCLUSION: No differences were identified between responders and non-responders to Fampridine treatment regarding physical and cognitive performance, neurophysiological or MRI outcomes. The results call for cautious interpretation and further large-scale studies are needed to expand ourunderstanding of underlying mechanisms discriminating Fampridine responders and non-responders.CMCT may be used as a marker of disability and walking impairment, while SDMT was associated with white matter lesions estimated by MRI. ClinicalTrials.gov identifier: NCT03401307

Clinical Study Interferon Alpha Association with Neuromyelitis Optica

Interferon-alpha (IFN-) has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN-in neuromyelitis optica (NMO) patients. Thirty-six NMO and 41 multiple sclerosis (MS) patients from a population-based retrospective case series were included. Expanded Disability Status Scale (EDSS) score and MRI findings determined disease activity. Linear regression was used to assess the effects of the level of IFN-on disability (EDSS). IFN-was determined by sensitive ELISA assays. IFN-was detectable in sera from 9/36 NMO patients, significantly more often than in the MS group (2/41) ( = 0.0197). A higher frequency of IFN-was observed in NMO patients with acute relapse compared to NMO patients in remission ( &lt; 0.001) and compared to the MS patients with relapse ( = 0.010). In NMO patients, the levels of IFN-were significantly associated with EDSS ( = 0.0062). It may be concluded that IFN-was detectable in a subgroup of NMO patients. Association of IFN-levels with clinical disease activity and severity suggests a role for IFN-in disease perpetuation and may provide a plausible explanation for a negative effect of IFN-1 treatment in NMO patients

Magnetic resonance imaging outcomes from a phase III trial of teriflunomide

Objective: The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis (MS) pathology inferred by magnetic resonance imaging (MRI). Methods: Patients ( n=1088) with relapsing MS were randomized to once-daily teriflunomide 7 mg or 14 mg, or placebo, for 108 weeks. MRI was recorded at baseline, 24, 48, 72 and 108 weeks. Annualized relapse rate and confirmed progression of disability (sustained ≥12 weeks) were the primary and key secondary outcomes. The principal MRI outcome was change in total lesion volume. Results: After 108 weeks, increase in total lesion volume was 67.4% ( p=0.0003) and 39.4% ( p=0.0317) lower in the 14 and 7 mg dose groups versus placebo. Other measures favoring teriflunomide were accumulated enhanced lesions, combined unique activity, T2-hyperintense and T1-hypointense component lesion volumes, white matter volume, and a composite MRI score; all were significant for teriflunomide 14 mg and most significant for 7 mg versus placebo. Conclusions: Teriflunomide provided benefits on brain MRI activity across multiple measures, with a dose effect evident on several markers. These effects were also consistent across selected subgroups of the study population. These findings complement clinical data showing significant teriflunomide-related reductions in relapse rate and disease progression, and demonstrate containment of MRI-defined disease progression

Short and Long Term Variation in Ultraviolet Radiation and Multiple Sclerosis

We examined the role of ultraviolet radiation (UVR) in persons diagnosed with multiple sclerosis (MS) in four different populations, Italians, Danish, White and African Americans. We tested whether variation in UVR as determined by seasons (short term variation) and solar cycles (long term variation) is related to MS birth month and to survival as measured by lifespan. Cases were selected from three Italian MS Case Registries (2,737); from the United States National Center for Health Statistics (56,020); and from the Danish Multiple Sclerosis registry (15,900). Chi-square tests were used to study the pattern of month of birth distribution in patients with MS comparing with general population data. T-tests were employed to study solar cycles association with lifespan. A surplus of births was observed in June for White Americans. A decrease of births in October and November, though not significant after multiple testing correction, was observed in the three populations. In White American with MS overall, males and females, we found that solar cycle is associated with lifespan. We found that season and solar cycles have some role in MS susceptibility and life duration. However, this is an exploratory analysis and further work is needed to discern the association

Mobile Phones and Multiple Sclerosis – A Nationwide Cohort Study in Denmark

We investigated the risk of, prognosis of and symptoms of multiple sclerosis (MS) among all Danish residents who owned a mobile phone subscription before 1996. Using the Danish Multiple Sclerosis Registry and Civil Registration System, study subjects were followed up for MS through 2004. Poisson models were used to calculate incidence rate ratios (IRR, age range: 18–64 years) and mortality rate ratios (MRR, age range: 18+) and to compare presenting symptoms among subscribers and all non-subscribers. A total of 405 971 subscription holders accrued four million years of follow up, with men accounting for 86% of the observation time. Among subscription holding men, the IRR of MS was close to unity, overall as well as 13+ years after first subscription (IRR 1.02, 95% CI: 0.48–2.16). Among women, the IRR was 3.43 (95% CI: 0.86–13.72) 13+ years after first subscription, however, based on only two cases. Presenting symptoms of MS differed between subscribers and non-subscribers (p = 0.03), with slightly increased risk of diplopia in both genders (IRR: 1.38, 95% CI: 1.02–1.86), an increased risk of fatigue among women (IRR: 3.02, 95% CI: 1.45–6.28), and of optic neuritis among men (IRR: 1.38, 95% CI: 1.03–1.86). Overall the MRR was close to one (MRR: 0.91, 95%CI 0.70–1.19) among MS-patients with a subscription and although we observed some increased MRR estimates among women, these were based on small numbers. In conclusion, we found little evidence for a pronounced association between mobile phone use and risk of MS or mortality rate among MS patients. Symptoms of MS differed between subscribers and nonsubscribers for symptoms previously suggested to be associated with mobile phone use. This deserves further attention, as does the increased long-term risk of MS among female subscribers, although small numbers and lack of consistency between genders prevent causal interpretation