Alemtuzumab improves quality-of-life outcomes compared with subcutaneous interferon beta-1a in patients with active relapsing-remitting multiple sclerosis.

BACKGROUND: Alemtuzumab was superior on clinical and magnetic resonance imaging (MRI) outcomes versus subcutaneous interferon beta-1a in phase 3 trials in patients with relapsing-remitting multiple sclerosis. OBJECTIVE: To examine quality-of-life (QoL) outcomes in the alemtuzumab phase 3 trials. METHODS: Patients who were treatment naive (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis I [CARE-MS I]) or had an inadequate response to prior therapy (CARE-MS II) received annual courses of alemtuzumab 12 mg/day at baseline (5 days) and Month 12 (3 days) or subcutaneous interferon beta-1a 44 µg three times/week. QoL was measured every 6 or 12 months using Functional Assessment of Multiple Sclerosis (FAMS), European Quality of Life-5 Dimensions (EQ-5D) and its visual analog scale (EQ-VAS), and 36-Item Short-Form Survey (SF-36). RESULTS: Statistically significant improvements from baseline with alemtuzumab were observed on all three QoL instruments at the earliest post-baseline assessment and sustained through Year 2. Statistically significant greater QoL improvements over subcutaneous interferon beta-1a were seen at all time points in CARE-MS II with FAMS, EQ-VAS and SF-36 physical component summary, and in CARE-MS I with FAMS. CONCLUSION: Patients treated with alemtuzumab had improvements in physical, mental, and emotional QoL regardless of treatment history. Improvements were significantly greater with alemtuzumab versus subcutaneous interferon beta-1a on both disease-specific and general measures of QoL.

Impact of a switch to fingolimod versus staying on glatiramer acetate or beta interferons on patient- and physician-reported outcomes in relapsing multiple sclerosis: post hoc analyses of the EPOC trial.

BACKGROUND: The Evaluate Patient OutComes (EPOC) study assessed physician- and patient-reported outcomes in individuals with relapsing multiple sclerosis who switched directly from injectable disease-modifying therapy (iDMT; glatiramer acetate, intramuscular or subcutaneous interferon beta-1a, or interferon beta-1b) to once-daily, oral fingolimod. Post hoc analyses evaluated the impact of a switch to fingolimod versus staying on each of the four individual iDMTs. METHODS: Overall, 1053 patients were randomized 3:1 to switch to fingolimod or remain on iDMT. The primary endpoint was the change in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction score. Secondary endpoints included changes in scores for TSQM Effectiveness, Side Effects and Convenience subscales, Beck Depression Inventory-II (BDI-II), Fatigue Severity Scale (FSS), Patient-Reported Outcome Indices for Multiple Sclerosis (PRIMUS) Activities, 36-item Short-Form Health Survey (SF-36) Mental Component Summary (MCS) and Physical Component Summary (PCS) and mean investigator-reported Clinical Global Impressions of Improvement (CGI-I). All outcomes were evaluated after 6 months of treatment. RESULTS: Changes in TSQM Global Satisfaction scores were superior after a switch to fingolimod when compared with scores in patients remaining on any of the iDMTs (all p <0.001). Likewise, all TSQM subscale scores improved following a switch to fingolimod (all p <0.001), except when compared with glatiramer acetate for the TSQM Side Effects subscale (p = 0.111). FSS scores were found to be superior for fingolimod versus remaining on subcutaneous interferon beta-1a and interferon beta-1b, BDI-II scores were significantly improved for fingolimod except for the comparison with intramuscular interferon beta-1a, and SF-36 scores were superior with fingolimod compared with remaining on interferon beta-1b (MCS and PCS; p = 0.030 and p = 0.022, respectively) and subcutaneous interferon beta-1a (PCS only; p = 0.024). Mean CGI-I scores were superior with fingolimod when compared with continuing treatment with any of the iDMTs (all p <0.001). CONCLUSIONS: After 6 months, a switch to fingolimod showed superiority compared with remaining on each iDMT for a range of patient- and physician-reported outcomes, including global satisfaction with treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT01216072 .

Practical Considerations for Managing Pregnancy in Patients With Multiple Sclerosis: Dispelling the Myths.

Purpose of Review: Lack of consistent data and guidance have led to variations between clinicians in the management of pregnancy in women with multiple sclerosis (MS). Pregnant and/or lactating women are often excluded from clinical trials conducted in MS, and thus, the labeling for most disease-modifying therapies (DMTs) excludes use during pregnancy. This has led to heterogeneity in interpretation and labeling regarding the safety of DMTs during pregnancy and lactation and the required preconception washout periods. This review identifies key themes where there is conflicting information surrounding family planning and pregnancy in MS, focusing on the most common discussion points between physicians and patients during preconception planning, pregnancy, postpartum, and lactation. The goal was to inform the patient-physician conversation and provide best practice recommendations based on expert clinical expertise and experience. Recent Findings: We outline the latest evidence-based data for DMT use during pregnancy and lactation, the effect of MS on fertility and fertility treatments, the risk of adverse pregnancy and delivery outcomes, the risk of postpartum relapse, and immunization and clinical imaging safety during pregnancy and breastfeeding. Summary: Management of family planning and pregnancy in patients with MS requires the most current information. Health care providers should discuss family planning early and frequently with patients with MS, and partners where practicable. Because management of pregnant people with MS will often require a risk/benefit analysis of their needs, shared decision-making in family planning discussions is emphasized. Additional data are needed for specific and underrepresented populations with MS (e.g., single parents or those from the LGBTQ+ community) and those at risk of racial and socioeconomic disparities in care. Pregnancy registries and the design and conduct of clinical trials focused on pregnant and lactating patients should provide additional data to guide the ongoing management of patients with MS.

Managing the symptoms of multiple sclerosis: a multimodal approach.

BACKGROUND: Patients with multiple sclerosis (MS) may experience numerous symptoms, including spasticity, fatigue, cognitive dysfunction, depression, bladder dysfunction, bowel dysfunction, sexual dysfunction, and pain. OBJECTIVE: This article reviews the pharmacologic and nonpharmacologic interventions used to manage the symptoms of MS and discusses how interventions for a particular MS symptom may have an impact on other symptoms. METHODS: The English-language literature was reviewed through November 2005 using MEDLINE and the Cochrane Database of Systematic Reviews, with no restriction on year. The search terms included multiple sclerosis, disease-modifying therapies, adverse events, and combinations of multiple sclerosis with terms such as spasticity, fatigue, depression, mood disorders, pain, bladder dysfunction, bowel dysfunction, sexual dysfunction, cognitive dysfunction, and quality of life. RESULTS: The numerous options for the treatment of MS symptoms have shown varying degrees of efficacy and tolerability. Certain symptoms, if left untreated, may precipitate exacerbation of others. For example, spasticity may lead to pain and bladder and bowel dysfunction, whereas fatigue can compromise cognitive function. Similarly, the adverse effects of treatments for certain symptoms may further compromise other aspects of function. For example, the use of antidepressants may lead to sexual dysfunction, and treatments for spasticity and pain may cause sedation, which can worsen fatigue, cognitive dysfunction, and depressed mood. CONCLUSIONS: MS is associated with numerous symptoms that can be adversely affected by each other and by therapeutic interventions. Careful clinical monitoring and individualization of pharmacologic and non-pharmacologic therapies are recommended to manage the symptoms of MS, with the goals of improving or maintaining function and preserving the patient's quality of life.

Patient perspectives and experience with dalfampridine treatment in multiple sclerosis-related walking impairment: the step together program.

BACKGROUND: Dalfampridine extended-release tablets (dalfampridine-ER; in Europe, prolonged-release fampridine, and elsewhere, fampridine modified or fampridine sustained release), 10 mg twice daily, are available for the treatment of improvement of walking in patients with multiple sclerosis, as demonstrated by an increase in walking speed. On-drug patient perspectives and experiences are valuable to understand and manage this patient population. OBJECTIVE: The objective of this study was to examine perspectives and experiences of patients receiving dalfampridine-ER in a real-world setting. METHODS: Step Together, an ongoing program that captures real-world patient experience with dalfampridine-ER treatment, consists of a survey administered at baseline (before dalfampridine-ER initiation) and at 30 (first follow-up) and 60 days (second follow-up) after initiation. The survey includes modified versions of the 12-item Multiple Sclerosis Walking Scale (mMSWS-12) and the Sheehan Disability Scale (mSDS) to assess walking ability and functional impairment, respectively. RESULTS: As of September 2013, 2,248 patients participated in the baseline survey and 522 completed both follow-up surveys (completers). Among the completers, improvements in walking ability and function relative to baseline were significant at both follow-ups as measured by mMSWS-12 and mSDS scores, respectively. Notably, 69-74 % of completers at both follow-ups had improved mMSWS-12 scores, with scores greater than the range considered to be minimally clinically significant. Patients who completed the program expressed satisfaction with overall dalfampridine-ER treatment, and 69 % indicated that the survey would help them communicate better with their healthcare providers. CONCLUSION: Results highlight the utility of patient-reported outcomes in the assessment of patient perspective and experience, providing a useful supplement to traditional objective measures used in clinical studies.

Outcomes of switching directly to oral fingolimod from injectable therapies: Results of the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis.

BACKGROUND: The Evaluate Patient OutComes (ClinicalTrials.gov Identifier: NCT01216072) study was conducted in North America to assess patient- and physician-reported treatment satisfaction in patients with relapsing multiple sclerosis (MS) who received oral fingolimod for 6 months after switching from an injectable disease-modifying therapy (iDMT), without an intervening washout. METHODS: In this open-label, multicenter study, patients were randomized 3:1 to once-daily fingolimod 0.5mg or iDMT. The primary study objective was to evaluate differences in satisfaction measured using the Treatment Satisfaction Questionnaire for Medication v1.4. RESULTS: Of 1053 patients randomized, 790 patients received fingolimod and 263 patients received iDMT. Treatment satisfaction improved significantly in patients who switched to fingolimod compared with those who continued iDMT. Patients also reported significant improvements in health-related quality of life, reduced depression, and reduced fatigue severity after a switch to fingolimod. No difference between the treatment groups was detected on the Patient Reported Indices for MS Activities scale. The safety profile of fingolimod was consistent with that reported in the pivotal phase 3 studies. The most commonly reported adverse events were more prevalent in patients who switched to fingolimod than in those who continued iDMT (headache: 12% vs 3%; fatigue: 12% vs 6%). No significant relationship between lymphocyte counts and infection rates was observed and there was no evidence of additive immune-system effects, which might be expected when switching to a different class of immunomodulatory therapy with no intervening washout. CONCLUSION: Patients who switched from iDMT to fingolimod had significant improvements in most self-reported outcomes compared with those who continued iDMT.

A multimodal approach to managing the symptoms of multiple sclerosis.

Multiple sclerosis (MS) is a disease of the CNS with a challenging clinical course characterized by heterogeneous symptoms related to inflammation and demyelination. Disease-modifying agents (DMAs) are used to treat the related neuronal degradation. Certain symptoms occur regularly, although with variable frequency, regardless of treatment with DMAs. Because there is no cure for MS at this time, symptom management is critically important to quality of life. Symptoms commonly seen are spasticity, fatigue, sexual dysfunction, bladder dysfunction, pain, and cognitive dysfunction. Other symptoms include depression, bowel dysfunction, paroxysmal symptoms, and weakness. The symptom management model that provides optimal results for patients with MS is a multimodal approach using effective communication, patient education, physical modalities and activities, occupational and other therapies, and pharmacologic interventions. Individualizing treatment for each patient involves gaining control of symptoms as early as possible to prevent cycles of symptoms from developing.