Interferon beta-1a sc at 25 years: a mainstay in the treatment of multiple sclerosis over the period of one generation.

INTRODUCTION: Interferon beta (IFN beta) preparations are an established group of drugs used for immunomodulation in patients with multiple sclerosis (MS). Subcutaneously (sc) applied interferon beta-1a (IFN beta-1a sc) has been in continuous clinical use for 25 years as a disease-modifying treatment. AREAS COVERED: Based on data published since 2018, we discuss recent insights from analyses of the pivotal trial PRISMS and its long-term extension as well as from newer randomized studies with IFN beta-1a sc as the reference treatment, the use of IFN beta-1a sc across the patient life span and as a bridging therapy, recent data regarding the mechanisms of action, and potential benefits of IFN beta-1a sc regarding vaccine responses. EXPERT OPINION: IFN beta-1a sc paved the way to effective immunomodulatory treatment of MS, enabled meaningful insights into the disease process, and remains a valid therapeutic option in selected vulnerable MS patient groups.

Oral pulsed therapy of relapsing multiple sclerosis with cladribine tablets - expert opinion on issues in clinical practice.

BACKGROUND: Oral cladribine is the first oral pulsed therapy licensed for relapsing multiple sclerosis (RMS). Three years after the introduction into the European market, we evaluated practical aspects in the use of cladribine tablets, incorporating the experience gained in routine clinical practice and real-world studies. METHODS: Based on a structured review process, a panel of nine neurologists experienced in MS therapy discussed salient statements regarding the use of cladribine tables. For each statement the level of evidence was determined according to the levels of evidence recommended by the Centre for Evidence-Based Medicine, Oxford. The strength of each expert statement was then evaluated by means of a linear scale from 1 (very strong rejection) to 9 (very strong approval). Votes were collected by a formalized blinded process. Consent was considered to be reached if at least 75% of the experts agreed on a particular statement (i.e. voted for 7-9 points on the linear scale). RESULTS: . Statements include efficacy in early RMS, risk of side effects and infections, vaccination, pregnancy, and monitoring requirements. CONCLUSION: The consented recommendations summarize the practical experience inthe use of cladribine tablets in a real-world setting. These may provide guidance for unanswered questions arising with the introduction of new treatments such as cladribine tablets.

Effects of Menopause in Women With Multiple Sclerosis: An Evidence-Based Review.

Over two thirds of all individuals who develop multiple sclerosis (MS) will be women prior to the age of menopause. Further, an estimated 30% of the current MS population consists of peri- or postmenopausal women. The presence of MS does not appear to influence age of menopausal onset. In clinical practice, symptoms of MS and menopause can frequently overlap, including disturbances in cognition, mood, sleep, and bladder function, which can create challenges in ascertaining the likely cause of symptoms to be treated. A holistic and comprehensive approach to address these common physical and psychological changes is often suggested to patients during menopause. Although some studies have suggested that women with MS experience reduced relapse rates and increased disability progression post menopause, the data are not consistent enough for firm conclusions to be drawn. Mechanisms through which postmenopausal women with MS may experience disability progression include neuroinflammation and neurodegeneration from age-associated phenomena such as immunosenescence and inflammaging. Additional effects are likely to result from reduced levels of estrogen, which affects MS disease course. Following early retrospective studies of women with MS receiving steroid hormones, more recent interventional trials of exogenous hormone use, albeit as oral contraceptive, have provided some indications of potential benefit on MS outcomes. This review summarizes current research on the effects of menopause in women with MS, including the psychological impact and symptoms of menopause on disease worsening, and the treatment options. Finally, we highlight the need for more inclusion of MS patients from underrepresented racial and geographic groups in clinical trials, including among menopausal women.

Incidence and mitigation of gastrointestinal events in patients with relapsing-remitting multiple sclerosis receiving delayed-release dimethyl fumarate: a German phase IV study (TOLERATE).

BACKGROUND: Gastrointestinal (GI) events are common adverse events (AEs) associated with delayed-release dimethyl fumarate (DMF), an approved treatment for relapsing-remitting multiple sclerosis (RRMS). The objective of the TOLERATE study was to evaluate GI tolerability and GI mitigation via symptomatic therapies in patients initiating DMF in a real-world clinical setting in Germany. METHODS: TOLERATE was a multicentre, open-label, single-arm study performed at 25 German sites. Endpoints were frequency, severity, duration (all primary) and mitigation of GI-related events (secondary). Patients were instructed to take DMF according to the prescribing information for up to 12 weeks and to document GI events and intake of GI-symptomatic therapy on numerical rating scales, using eDiaries. RESULTS: A total of 211 patients were included in the safety population (71% female; mean age 40 ± 11 years). Of these, 185 patients (87.7%) reported GI-related events, out of which nearly half received GI-symptomatic therapy (84/185; 45.4%). The most frequently reported GI events were upper abdominal pain, flatulence and nausea. GI-related events peaked during the first 3 weeks of therapy and rapidly decreased thereafter. The severity of GI events over 12 weeks according to the Modified Overall Gastrointestinal Symptom Scale were mild to moderate in the majority of patients reporting GI-related events and taking symptomatic GI medication (53.6%). Only 10% of all patients discontinued study treatment due to AEs in general, while 6.6% discontinued due to GI-related events. The severity of GI-related events decreased over time in patients who received symptomatic treatment with one or more medications (e.g. acid secretion blockers, antidiarrhoeals or antiemetics). CONCLUSION: Gastrointestinal events associated with delayed-release DMF were mainly mild to moderate in severity. Prevalence of GI events peaked during the first 3 weeks of therapy and rapidly faded thereafter. Although 44.9% of patients experiencing GI events used common GI symptomatic therapies, only 6.6% of patients discontinued DMF because of GI events, suggesting that GI events could be managed well with common symptomatic therapy.

Exclusive Breastfeeding and the Effect on Postpartum Multiple Sclerosis Relapses.

IMPORTANCE: Women with multiple sclerosis (MS) experience an elevated risk of relapse after giving birth. The effect of exclusive breastfeeding on postpartum risk of MS relapse is unclear. OBJECTIVES: To determine the effect of exclusive breastfeeding on postpartum risk of MS relapse and to investigate the effect of introducing supplemental feedings on that risk. DESIGN, SETTING, AND PARTICIPANTS: Data on 201 pregnant women with relapsing-remitting MS were collected prospectively from January 1, 2008, to June 30, 2012, with 1 year follow-up post partum in the nationwide German MS and pregnancy registry. The effect of the intention to breastfeed exclusively (no regular replacement of breastfeeding meals with supplemental feedings) for at least 2 months compared with nonexclusive breastfeeding (partial or no breastfeeding) on the first postpartum MS relapse, using Cox proportional hazards regression model adjusted for age and disease activity, before and during pregnancy was analyzed. Data analysis was performed from August 30, 2013, to May 25, 2015. EXPOSURE: Exclusive breastfeeding defined as at least 2 months of breastfeeding without regular replacement of any meal by supplemental feeding. MAIN OUTCOME AND MEASURE: First postpartum MS relapse. RESULTS: Of 201 women, 120 (59.7%) intended to breastfeed exclusively for at least 2 months and 81 (40.3%) breastfed and included supplemental feeding (42 [20.9%]) or did not breastfeed (39 [19.4%]). Thirty-one women (38.3%) who did not breastfeed exclusively had a relapse within the first 6 months post partum compared with 29 women (24.2%) who intended to breastfeed exclusively for at least 2 months (unadjusted hazard ratio, 1.80; 95% CI, 1.09-2.99; P = .02; adjusted hazard ratio, 1.70; 95% CI, 1.02-2.85; P = .04). The time to first postpartum relapse after the introduction of supplemental feedings did not differ significantly between women who previously breastfed exclusively and those who did not (P = .60). CONCLUSIONS AND RELEVANCE: The findings of this study suggest that exclusive breastfeeding is a modestly effective MS treatment with a natural end date. Our study provides further evidence that women with MS who breastfeed exclusively should be supported to do so since it does not increase the risk of postpartum relapse.

Natalizumab use during the third trimester of pregnancy.

IMPORTANCE: Natalizumab reduces multiple sclerosis relapses very effectively; however, severe disease activity may return once natalizumab treatment is withdrawn, as recommended during pregnancy. Sometimes restarting natalizumab treatment may be the best option for the mother, but the consequences for the infant are unknown. Except for a few single case reports, to our knowledge, comprehensive data about third-trimester natalizumab exposure are scant. OBSERVATIONS: In a case series of 12 women with 13 pregnancies and highly active multiple sclerosis who were treated with natalizumab during their third trimester of pregnancy, we assessed the clinical and laboratory effects on the newborns. We observed mild to moderate hematologic alterations in 10 of 13 infants including thrombocytopenia and anemia. In a subsample of 5 mother-child pairs, we analyzed natalizumab levels in the umbilical cord blood. Natalizumab was detectable in all 5 newborns. CONCLUSION AND RELEVANCE: Natalizumab can be a therapeutic option in patients with highly active multiple sclerosis during pregnancy. We recommend that a pediatrician be available at the time of delivery to evaluate for potential complications of anemia and thrombocytopenia in newborns exposed to natalizumab during the third trimester.