Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: A pilot randomized controlled trial.

Background: Patients with MS have an altered gut microbiota compared to healthy individuals, as well as elevated small intestinal permeability, which may be contributing to the development and progression of the disease. Objective: We sought to investigate if fecal microbiota transplantation was safe and tolerable in MS patients and if it could improve abnormal intestinal permeability. Methods: Nine patients with MS were recruited and provided monthly FMTs for up to six months. The primary outcome investigated was change in peripheral blood cytokine concentrations. The secondary outcomes were gut microbiota composition, intestinal permeability, and safety (assessed with EDSS and MRI). Results: The study was terminated early and was subsequently underpowered to assess whether peripheral blood cytokines were altered following FMTs. FMTs were safe in this group of patients. Two of five patients had elevated small intestinal permeability at baseline that improved to normal values following FMTs. Significant, donor-specific, beneficial alterations to the MS patient gut microbiota were observed following FMT. Conclusion: FMT was safe and tolerable in this cohort of RRMS patients, may improve elevated small intestinal permeability, and has the potential to enrich for an MS-protective microbiota. Further studies with longer follow-up and larger sample sizes are required to determine if FMT is a suitable therapy for MS.

Predictive validity of NEDA in the 16- and 21-year follow-up from the pivotal trial of interferon beta-1b.

BACKGROUND: Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) permitted the assessment of different definitions of no evidence of disease activity (NEDA) for predicting long-term outcome in multiple sclerosis (MS). OBJECTIVE: To examine the predictive validity of different NEDA definitions. METHODS: Predictive validity for negative disability outcomes (NDOs) at 16 years and survival at 21 years post-randomization were assessed. NEDA in the first 2 years was defined as follows: clinical NEDA: no relapses or Expanded Disability Status Scale (EDSS) progression from baseline to Year 2; NEDA-3a: no relapses, no confirmed ⩾1-point EDSS progression, and no new T2-active lesions; NEDA-3b: no relapses, no EDSS progression, and no increase in T2 burden of disease (T2-BOD); and NEDA-4: no relapses, no EDSS progression, and no increase in T2-BOD or atrophy. NDOs were defined as death, need for wheelchair, EDSS ⩾6, or progressive MS. RESULTS: A total of 245 and 371 patients were evaluated at 16 and 21 years, respectively. Clinical NEDA predicted NDOs ( p = 0.0029), as did baseline EDSS ( p < 0.0001), baseline T2-BOD ( p < 0.0001), and change in T2-BOD ( p = 0.0033). IFNB-1b treatment ( p = 0.0251), relapse rate in the 2 years before study start ( p = 0.0260), T2-BOD at baseline ( p = 0.0014), and change in T2-BOD ( p = 0.0129) predicted survival at 21 years. CONCLUSION: Clinical NEDA predicted long-term disability outcome. By contrast, definitions of NEDA that included on-therapy changes in magnetic resonance imaging variables did not increase the predictive validity.

Long-term outcomes of peginterferon beta-1a in multiple sclerosis: results from the ADVANCE extension study, ATTAIN.

BACKGROUND: ADVANCE was a phase III trial of the efficacy and safety of subcutaneous peginterferon beta-1a 125 µg every 2 or 4 weeks in patients with relapsing-remitting multiple sclerosis (RRMS). ATTAIN was a 2-year extension study of ADVANCE. The aim was to evaluate the long-term safety, tolerability, and efficacy of peginterferon beta-1a 125 µg every 2 or 4 weeks in ATTAIN. METHODS: ADVANCE dosing schedules were maintained in ATTAIN, except that every-4-weeks dosing patients were switched to every-2-weeks dosing after conversion of the study to an open-label protocol. ATTAIN was considered complete when the last patient completed the 96-week extension study. Primary endpoints included adverse event (AE) and serious AE (SAE) incidence. Secondary endpoints included relapse, magnetic resonance imaging, and disability outcomes. RESULTS: Of the 1512 patients randomized in ADVANCE, 1076 (71%) continued treatment in ATTAIN; of these, 842 (78%) completed the open-label extension study. During ATTAIN, 478 patients (87%) in the every-2-weeks group and 471 patients (89%) in the every-4-weeks group experienced an AE; SAEs were reported in 90 patients (16%) in the every-2-weeks group and 113 patients (21%) in the every-4-weeks group. The most frequent AEs reported were injection site reactions and flu-like symptoms, both of which numerically decreased over time. Peginterferon beta-1a every 2 weeks versus every 4 weeks significantly reduced the adjusted annualized relapse rate over 6 years (0.188 versus 0.263, p = 0.0052) and the risk of relapse over 5 years (36% versus 49%, p = 0.0018). Fewer new T1, new/newly enlarging T2, and gadolinium-enhancing magnetic resonance imaging lesions were observed with every-2-weeks dosing than every-4-weeks dosing over 4 years. CONCLUSIONS: Results from the ADVANCE extension study, ATTAIN, confirm the favorable long-term safety and tolerability profile of peginterferon beta-1a in patients with RRMS and provide additional evidence for the clinical and radiological benefits associated with this therapy.

Common variation near IRF6 is associated with IFN-ß-induced liver injury in multiple sclerosis.

Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-ß (IFN-ß). Up to 60% of IFN-ß-exposed MS patients develop abnormal biochemical liver test results1,2, and 1 in 50 experiences drug-induced liver injury3. Since genomic variation contributes to other forms of drug-induced liver injury4,5, we aimed to identify biomarkers of IFN-ß-induced liver injury using a two-stage genome-wide association study. The rs2205986 variant, previously linked to differential expression of IRF6, surpassed genome-wide significance in the combined two-stage analysis (P = 2.3 × 10-8, odds ratio = 8.3, 95% confidence interval = 3.6-19.2). Analysis of an independent cohort of IFN-ß-treated MS patients identified via electronic medical records showed that rs2205986 was also associated with increased peak levels of aspartate aminotransferase (P = 7.6 × 10-5) and alkaline phosphatase (P = 4.9 × 10-4). We show that these findings may be applicable to predicting IFN-ß-induced liver injury, offering insight into its safer use.

Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial.

Importance: Intravenous (IV) administration of corticosteroids is the standard of care in the treatment of acute optic neuritis. However, it is uncertain whether a bioequivalent dose of corticosteroid administered orally, which may be more cost-efficient and convenient for patients, is as effective as IV administration in the treatment of acute optic neuritis. Objective: To determine whether recovery of vision following treatment of acute optic neuritis with a high-dose IV corticosteroid is superior to that with a bioequivalent dose of an oral corticosteroid. Design, Setting, and Participants: This single-blind (participants unblinded) randomized clinical trial with 6-month follow-up was conducted at a single tertiary care center in London, Ontario, Canada. Participants were enrolled from March 2012 to May 2015, with the last participant's final visit occurring November 2015. Patients 18 to 64 years of age presenting within 14 days of acute optic neuritis onset, without any recovery at time of randomization and without history of optic neuritis in the same eye, were screened. Inclusion criteria included best-corrected visual acuity (BCVA) of 20/40 or worse and corticosteroids deemed required by treating physician. In total, 89 participants were screened; 64 were eligible, but 9 declined to participate. Thus, 55 participants were enrolled and randomized. Primary analysis was unadjusted and according to the intention-to-treat principle. Interventions: Participants were randomized 1:1 to the IV methylprednisolone sodium succinate (1000-mg) or oral prednisone (1250-mg) group. Main Outcomes and Measures: Primary outcome was recovery of the latency of the P100 component of the visual evoked potential at 6 months. Secondary outcomes were the P100 latency at 1 month and BCVA as assessed with Early Treatment Diabetic Retinopathy Study letter scores on the alphabet chart and scores on low-contrast letters at 1 and 6 months. Results: Of 55 randomized participants, the final analyzed cohort comprised 23 participants in the IV and 22 in the oral treatment groups. The mean (SD) age of the cohort was 34.6 (9.5) years, and there were 28 women (62.2%). At 6 months' recovery, P100 latency in the IV group improved by 62.9 milliseconds (from a mean [SD] of 181.9 [53.6] to 119.0 [16.5] milliseconds), and the oral group improved by 66.7 milliseconds (from a mean [SD] of 200.5 [67.2] to 133.8 [31.5] milliseconds), with no significant difference between groups (P = .07). Similarly, no significant group difference was found in the mean P100 latency recovery at 1 month. For BCVA, recovery between the groups did not reach statistical significance at 1 month or 6 months. In addition, improvements in low-contrast (1.25% and 2.5%) BCVA were not significantly different between treatment groups at 1 or 6 months' recovery. Conclusions and Relevance: This study finds that bioequivalent doses of oral corticosteroids may be used as an alternative to IV corticosteroids to treat acute optic neuritis. Trial Registration: clinicaltrials.gov Identifier: NCT01524250.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

BACKGROUND: On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis. METHODS: During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T2-weighted MRI, cumulative number of new lesions enhanced on T1-weighted MRI ["enhancing lesions"], and cumulative combined number of unique lesions [new enhancing lesions on T1-weighted MRI plus new and newly enlarged lesions on T2-weighted MRI]). RESULTS: A total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval [CI], 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95% CI, 3.7 to 33.3; P=0.01); the unadjusted risk difference was not significant at the 24-month secondary outcome time point (P=0.06). All secondary MRI outcomes favored minocycline over placebo at 6 months but not at 24 months. Trial withdrawals and adverse events of rash, dizziness, and dental discoloration were more frequent among participants who received minocycline than among those who received placebo. CONCLUSIONS: The risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).

Breaking down the gut microbiome composition in multiple sclerosis.

BACKGROUND: The gut microbiome, which consists of a highly diverse ecologic community of micro-organisms, has increasingly been studied regarding its role in multiple sclerosis (MS) immunopathogenesis. This review critically examines the literature investigating the gut microbiome in MS. METHODS: A comprehensive search was performed of PubMed databases and ECTRIMS meeting abstracts for literature relating to the gut microbiome in MS. Controlled studies examining the gut microbiome in patients with MS were included for review. RESULTS: Identified studies were predominantly case-control in their design and consistently found differences in the gut microbiome of MS patients compared to controls. We examine plausible mechanistic links between these differences and MS immunopathogenesis, and discuss the therapeutic implications of these findings. CONCLUSIONS: Review of the available literature reveals potential immunopathogenic links between the gut microbiome and MS, identifies avenues for therapeutic advancement, and emphasizes the need for further systematic study in this emerging field.

Canadian Experience with Fingolimod: Adherence to Treatment and Monitoring.

BACKGROUND: The Canadian GILENYA® Go ProgramTM provides education and support to people with relapsing-remitting multiple sclerosis during fingolimod treatment. METHODS: Data were collected and analyzed from the time of the first individual enrolled in March 2011 to March 31, 2014. Individuals were excluded if they withdrew from the program prior to receiving the first dose, or had not completed the first dose observation (FDO) at the time of data cut-off. Reports of adverse effects were validated with a database of adverse events reported to Novartis Pharmaceuticals Canada Inc. RESULTS: A total of 2,399 individuals had completed FDO at the end of the three-year observation period. Mean age was 41.2 years; 75.2% were female. The most recent prior therapies reported were interferon-ß agents (50.2%), glatiramer acetate (31.1%), natalizumab (14.2%), no prior therapy (3.3%), and other agent (1.1%). Reasons for switching to fingolimod were lack of efficacy (34.9%), side effects (34.6%), and dissatisfaction with injections/infusion (30.4%). Continuation rates with fingolimod at 12, 24 and 30 months were 80.7%, 76.6% and 76.0%, respectively. The discontinuation rate due to reported lack of efficacy during the three-year period was 1.3%. There was 94.4% adherence to the scheduled ophthalmic examination. CONCLUSIONS: The GILENYA® Go ProgramTM captures data for virtually all fingolimod-treated patients in Canada, enabling the evaluation of fingolimod use in routine practice. Ongoing patient support and reminders to take the medication, in conjunction with physicians' and/or patients' perception of the efficacy and tolerability of fingolimod, resulted in a high rate of continuation during longer-term therapy.

Consensus Management of Gastrointestinal Events Associated with Delayed-Release Dimethyl Fumarate: A Delphi Study.

INTRODUCTION: Delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF) is indicated for the treatment of patients with relapsing multiple sclerosis. Gastrointestinal (GI) adverse events (AEs) occur with DMF therapy. METHODS: We used a Delphi process to reach consensus among North American clinicians on effective real-world management strategies for GI AEs associated with DMF. Clinicians were asked to complete two rounds of questionnaires developed by a steering committee; consensus in round 2 was attained if ≥70% of respondents agreed on a particular strategy. RESULTS: Consensus was reached on several strategies to manage GI AEs, including administering DMF with food, slow titration, dose reduction, and use of symptomatic therapies. CONCLUSION: These consensus strategies provide clinicians with information on real-world approaches used to address the tolerability of DMF in patients with multiple sclerosis. FUNDING: Biogen.

Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15.

AIM: An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) ß-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing-remitting multiple sclerosis (RRMS). METHODS: Patients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN ß-1a dose groups, and according to total time receiving sc IFN ß-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed. RESULTS: Of 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS ≥ 4 or ≥ 6, ≤ 5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years. CONCLUSIONS: These findings suggest that higher cumulative exposure to sc IFN ß-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS.

Autonomic dysfunction in multiple sclerosis.

Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

Systematic review of efficacy of TENS for management of central pain in people with multiple sclerosis.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological therapy that can be used for central pain (CP) management without the side effects of pharmacological interventions. Currently, the efficacy of TENS for management of CP in people living with multiple sclerosis (MS) is considered questionable. METHODS: Relevant electronic databases were searched from their inception to November 2014 using appropriate terms for case-control (CC) studies or randomized controlled trials (RCTs) utilizing TENS for management of CP in MS. Included studies were combined in a meta-analysis. A standardized mean difference (SMD) expressed as Hedges׳ g and 95% confidence interval (CI) of efficacy of TENS intervention were computed using a random effects model. The resulting evidence was graded in accordance to the GRADE system. RESULTS: A total of 11 effect sizes were extracted from four studies. High and low frequency TENS was utilized in separate subgroup of participants in three studies and conventional TENS in one study. These seven effect sizes were combined for the final analysis (one effect size for each subgroup of participants). Two studies measured pain using visual analog scale and McGill Pain Questionnaire. The findings of this study demonstrate a medium sized statistically significant effect of TENS for management of CP in people with MS [Hedges׳ g=0.35; p=0.009]. The frequency of TENS or outcome used to measure pain had no effect on our study results. These findings are consistent with GRADE 2 level of evidence. CONCLUSION: TENS is a safe and effective non-pharmacological alternative in the management of central pain in people living with MS. TENS intervention to address CP is desirable.

Cardiovascular autonomic dysfunction in multiple sclerosis: a meta-analysis.

BACKGROUND AND OBJECTIVE: The definition of cardiovascular autonomic dysfunction in patients with multiple sclerosis is controversial. Thus, its true prevalence is unknown. We performed a systematic review and meta-analysis to compare the proportion of patients with multiple sclerosis that would be diagnosed with cardiovascular dysautonomia using a definition of at least one abnormal cardiac autonomic test vs. at least two abnormal studies. METHODS: We searched PubMed, Embase, and Scopus from 1980 to December 2013 for publications reporting abnormal autonomic tests in patients with multiple sclerosis. We performed random-effects meta-analyses for calculating the proportion of patients diagnosed with autonomic dysfunction with both definitions. RESULTS: We included 16 studies comprising 611 patients with multiple sclerosis, assessing ≥3 cardiovascular autonomic tests. The proportion of patients with autonomic dysfunction was two-fold higher (p=0.006) when using the definition of only one abnormal autonomic test (42.1%) compared to that using at least two abnormal results (18.8%). CONCLUSIONS: We found a wide variation in the proportion of patients with multiple sclerosis diagnosed with cardiovascular dysautonomia by using the two definitions. Consensus is needed to define autonomic dysfunction in patients with multiple sclerosis. In the meantime, we encourage investigators to report results using both thresholds.

Evolving role of MRI in optimizing the treatment of multiple sclerosis: Canadian Consensus recommendations.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly important for the early detection of suboptimal responders to disease-modifying therapy for relapsing-remitting multiple sclerosis. Treatment response criteria are becoming more stringent with the use of composite measures, such as no evidence of disease activity (NEDA), which combines clinical and radiological measures, and NEDA-4, which includes the evaluation of brain atrophy. METHODS: The Canadian MRI Working Group of neurologists and radiologists convened to discuss the use of brain and spinal cord imaging in the assessment of relapsing-remitting multiple sclerosis patients during the treatment course. RESULTS: Nine key recommendations were developed based on published sources and expert opinion. Recommendations addressed image acquisition, use of gadolinium, MRI requisitioning by clinicians, and reporting of lesions and brain atrophy by radiologists. Routine MRI follow-ups are recommended beginning at three to six months after treatment initiation, at six to 12 months after the reference scan, and annually thereafter. The interval between scans may be altered according to clinical circumstances. CONCLUSIONS: The Canadian recommendations update the 2006 Consortium of MS Centers Consensus revised guidelines to assist physicians in their management of MS patients and to aid in treatment decision making.

Characteristics associated with drug-induced liver injury from interferon beta in multiple sclerosis patients.

OBJECTIVE: To identify and characterize drug-induced liver injury (DILI) associated with IFN-ß in multiple sclerosis (MS) using recommended criteria. METHODS: This retrospective, mixed methods design included a cohort of IFN-ß exposed MS patients from British Columbia (BC), Canada and a series of DILI cases from other Canadian provinces and two adverse drug reaction (ADR) networks (USA and Sweden). Associations between sex, age and IFN-ß product, and DILI were explored in BC cohort using Cox proportional hazard analyses. Characteristics, including the time to DILI, were compared between sites. RESULTS: In BC, 18/942 (1.9%) of IFN-ß exposed MS patients met criteria for DILI, with a trend toward an increased risk for women and those exposed to IFN-ß-1a SC (44 mcg 3 × weekly) (adjusted Hazard Ratios: 3.15;95% CI:0.72 - 13.72, p = 0.13 and 6.26;95%CI:0.78 - 50.39, p = 0.08, respectively). Twenty-four additional cases were identified from other sites; the median time to DILI was comparable between BC and other Canadian cases (105 and 90 days, respectively), but longer for the ADR network cases (590 days, p = 0.006). CONCLUSIONS: Approximately 1 in 50 IFN-ß exposed patients developed DILI in BC, Canada. Identification of DILI cases from diverse sources highlighted that this reaction occurs even after years of exposure.

Multiple sclerosis: improved identification of disease-relevant changes in gray and white matter by using susceptibility-based MR imaging.

PURPOSE: To evaluate the potential of quantitative susceptibility (QS) and R2* mapping as surrogate biomarkers of clinically relevant, age-adjusted demyelination and iron deposition in multiple sclerosis (MS). MATERIALS AND METHODS: All study participants gave written informed consent, and the study was approved by the institutional review board. Quantitative maps of the magnetic resonance imaging susceptibility parameters (R2* and QS) were computed for 25 patients with either clinically isolated syndrome (CIS) or relapsing-remitting MS, as well as for 15 age- and sex-matched control subjects imaged at 7 T. The candidate MR imaging biomarkers were correlated with Extended Disability Status Scale (EDSS), time since CIS diagnosis, time since MS diagnosis, and age. RESULTS: QS maps aided identification of significant, voxel-level increases in iron deposition in subcortical gray matter (GM) of patients with MS compared with control subjects. These voxel-level increases were not observed on R2* maps. Region-of-interest analysis of mean R2* and QS in subcortical GM demonstrated that R2* (R ≥ 0.39, P < .01) and QS (R ≥ 0.44, P < .01) were strongly correlated with EDSS. In white matter (WM), the volume of total WM damage (defined by a z score of less than -2.0 criterion, indicating demyelination) on QS maps correlated significantly with EDSS (R = 0.46, P = .02). Voxelwise QS also supported a significant contribution of age to demyelination in patients with MS, suggesting that age-adjusted clinical scores may provide more robust measures of MS disease severity compared with non-age-adjusted scores. CONCLUSION: Using QS and R2* mapping, evidence of both significant increases in iron deposition in subcortical GM and myelin degeneration along the WM skeleton of patients with MS was identified. Both effects correlated strongly with EDSS.

Pegylated interferons: a nurses' review of a novel multiple sclerosis therapy.

Most multiple sclerosis (MS) therapies are injectable drugs, and the frequency of injections has been shown to be inversely proportional to overall compliance. One method of improving therapeutic compliance and thus clinical outcomes is to develop medications that require less frequent dosing. One of the most promising modification techniques to extend the bioavailability of a drug is poly(ethylene glycol) conjugation (pegylation), which increases the size of a molecule by attaching polyethylene glycol moieties to the parent compound, resulting in slower clearance and metabolism. This approach has been used to improve the efficacy of a number of therapeutic molecules, including interferons. Peginterferon beta-1a, a pegylated form of interferon beta-1a, is currently in phase III clinical trials for relapsing MS and has the potential to improve patient compliance by reducing the number of injections while maintaining clinical efficacy. The role of nurses in educating patients about the effective use of this new MS therapy is discussed.