Information on pregnancy and infant outcomes after cladribine tablets exposure is limited, as its use is not recommended during pregnancy. This is a summary of the original published article ‘Pregnancy and infant outcomes in multiple sclerosis: findings from the Global MAPLE-MS Pharmacovigilance Program’. The primary outcome is the prevalence of major congenital anomalies (MCAs) in babies. Secondary outcomes include other pregnancy outcomes (live birth, elective termination, spontaneous abortion, ectopic pregnancy, and stillbirth).

Myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are antibody-mediated neuroimmune disorders that frequently affect women in their reproductive years and require careful treatment planning around pregnancy. Disease exacerbations (for myasthenia gravis) and attacks (for NMOSD and MOGAD) can occur during pregnancy, are common postpartum, and can cause preventable, long-term maternal disability. Many drug labels are conservative or recommend unnecessary prolonged washouts or avoidance of breastfeeding, creating uncertainty for physicians and patients. This Personal View integrates available evidence on conventional immunosuppressants and biological therapies, including complement inhibition, B-cell depletion, and neonatal Fc receptor blockade. Although data on pregnancy safety for newer treatments are few, preliminary data suggest that selected therapies could be continued during pregnancy to maintain disease stability and are compatible with breastfeeding. We offer expert recommendations for therapy choice, infant vaccinations, and fetal and infant monitoring in myasthenia gravis, NMOSD, and MOGAD.

Abstract Background Neuromyelitis optica spectrum disorders (NMOSD) are associated with a high burden of depression, pain, and physical disability, all of which significantly impair quality of life. At the same time, discussions on the cost-effectiveness of treatment strategies are gaining importance. However, it is not yet known whether specific symptom burdens are particularly cost-driving. This study aims to provide a comprehensive cost analysis considering depression and pain to optimise future healthcare strategies. Methods This prospective cross-sectional multicentre study was conducted at twelve centres of the Neuromyelitis Optica Study Group (NEMOS). Over a three-year period, 115 NMOSD patients were recruited. Disease-related costs, pain, and depression were assessed using standardised questionnaires. A generalised linear model analysis and graphical sub-cost analysis were performed to identify key cost drivers. The robustness of our findings was confirmed using two independent depression rating scales. Results In our sample of 115 patients, 77% suffered from chronic pain with a median pain intensity of 4.0 on the numeric rating scale (NRS). Moreover, 56% of patients reported depressive symptoms. In multivariate regression analysis, depression emerged as a significant predictor of total costs (p < 0.001) alongside the EDSS score (p < 0.001) and age (p = 0.004). In contrast, pain was not significantly influencing total costs (p = 0.057), despite being reported by the majority of patients. Graphical analyses highlighted informal costs as the main cost driver in patients with increasing depressive symptoms. Conclusions Depressive symptoms are not only common in NMOSD patients but also represent a major cost driver alongside neurological disability. Addressing these symptoms is essential for optimal patient care and may help reduce the socioeconomic burden.

Purpose of Review:As the life expectancy of people with multiple sclerosis (PwMS) increases, the importance of recognizing and addressing specific needs and challenges faced by those undergoing age-related sex hormone changes and hypogonadism is becoming increasingly evident. We present expert-led, practical recommendations from a consensus program that address gaps in age-related sex hormone changes and hypogonadism in PwMS not sufficiently addressed in current literature and guidelines. A multidisciplinary steering committee (SC) of 15 international experts identified 18 key clinical questions across 6 themes: climacteric symptoms in women with MS; impact of MS on the climacteric stage; impact of menopause on MS disease activity and progression; treatment and management of climacteric symptoms in women with MS; late-onset hypogonadism (LOH) in men with MS; and patient-centered care. After thorough review of the evidence from a systematic literature review, the SC formulated 18 clinical recommendations to address the questions. These recommendations were voted on by the SC and an extended faculty of 23 health care professionals from 16 countries, including 2 nurses and 1 patient association representative. Recent Findings:Consensus was reached when ≥75% of respondents expressed agreement, with a score of 7-9 on a 9-point scale. After a single voting round, all 18 recommendations reached consensus (14 reaching consensus at 90%-100% and 4 at 80%-90%). The clinical recommendations addressed the following: the potential overlap and exacerbation of MS symptoms during the climacteric stage; the need for preventive care and screening during the menopausal transition; the potential for, and a paucity of data on, differential efficacy and tolerability of MS medications in menopausal/postmenopausal women; the complex causal interplay between hormonal and/or immunologic changes and natural aging in PwMS switching to a more progressive phase of disease; consideration of behavioral/lifestyle interventions alongside pharmacologic treatments; effects of hormonal treatments on MS symptoms; and management of LOH in men with MS. Summary:These recommendations were based on a robust modified Delphi consensus approach and present a valuable framework for improved patient care. These results emphasize the need to address critical gaps in our understanding and management of PwMS undergoing age-related sex hormone changes and hypogonadism.

OBJECTIVES:Vaccinations are important for patients with immune-mediated inflammatory diseases (IMID), including multiple sclerosis (MS), inflammatory rheumatic and musculoskeletal diseases (iRMD), or inflammatory bowel diseases (IBD). However, safety concerns persist regarding potential disease worsening. This study assessed the risk of IMID worsening requiring emergency hospitalization following pneumococcal or influenza vaccination. METHODS:In this retrospective population-based cohort study, six target trial emulations with time-dependent matching were performed using claims data from the German statutory health insurance BARMER from January 2013 to December 2019. Covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS:Of 432,768 IMID patients, 9526 MS, 108,422 iRMD, and 19,238 IBD patients were included in pneumococcal trials, and 30,416 MS, 265,850 iRMD, and 53,056 IBD patients in influenza trials. No increased risk was found; instead, a trend toward risk reduction was observed. Pneumococcal trials showed HRs of 0.91 [95% CI: 0.58-1.42] for MS, 0.60 [0.38-0.94] for iRMD, and 0.89 [0.62-1.26] for IBD. The influenza trials showed similar results (MS: 0.94 [0.73-1.21]; iRMD: 0.79 [0.63-1.00]; IBD: 0.83 [0.68-1.03]). CONCLUSIONS:No evidence of increased IMID worsening requiring emergency hospitalization after pneumococcal or influenza vaccination was found, supporting the safety of immunizing these patients.

OBJECTIVE:This article provides evidence-based advice to facilitate early, explicit, and continuous consideration of family planning, enabling effective treatment selection and allowing people living with neuroinflammatory disorders to balance disease control with optimal pregnancy outcomes. LATEST DEVELOPMENTS:There has been a paradigm shift in treatment approaches for women living with active neuroinflammatory disease who are considering pregnancy. Women with active multiple sclerosis are at risk of disabling relapse if immunosequestering therapy is withdrawn for pregnancy, making it essential that pregnancies are well planned. For those taking CD20-antibody or induction therapies, relapse rates remain suppressed during pregnancy with low postpartum relapse risk, even when treatment is discontinued during pregnancy and not directly restarted after birth. In patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), CD20 antibodies are increasingly used around pregnancy, with additional promising early data regarding the safety of eculizumab and interleukin-6 antibodies. All monoclonal antibodies used in multiple sclerosis, NMOSD, and MOGAD are potentially suitable for use during breastfeeding, particularly in women with more active prepregnancy disease, due to low rates of breakthrough relapses combined with an absence of breastmilk transfer. ESSENTIAL POINTS:Balancing disease control with pregnancy and neonatal considerations in people with neuroinflammatory disease throughout the family planning, pregnancy, and postpartum periods is crucial. Modern treatment paradigms enable women to safely become pregnant and breastfeed alongside effective disease management. Shared decision-making is an important part of this process.

Patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) have an increased risk of infections due to immunosuppression and autoimmune disease. While vaccinations are an important preventive strategy, vaccination coverage remains insufficient in Germany. The study aimed to identify barriers and facilitators for vaccination uptake from the perspective of iRMD patients, general practitioners (GPs), and rheumatologists. We conducted semi-structured, qualitative interviews with German iRMD patients (n = 15), GPs (n = 10), and rheumatologists (n = 5). Data were analyzed using Kuckartz’s structured content analysis. The analysis focused on attitudes towards vaccination, information needs, decision-making, and perceived role distribution in care. A trust-based doctor-patient relationship and consistent, comprehensible information promoted willingness to vaccinate. Barriers included uncertainties regarding immunosuppressants, unclear responsibilities between GPs and rheumatologists, and inconsistent or conflicting medical recommendations. Patients desired a proactive approach from physicians and clearly assigned responsibilities. Physicians emphasized interprofessional exchange but stated time and structural challenges. The results underline the importance of coordinated communication and clear responsibilities in the vaccination process for iRMD patients. To increase vaccination rates among patients with iRMD, the focus should be on targeted information services, improved allocation of tasks between GPs and rheumatologists, timely scheduling of vaccinations (ideally before initiating immunosuppressive therapy), clear responsibilities for initiating and coordination of vaccination, and a structured, transparent flow of evidence-based information between specialists. The results provide a basis for the development of practical intervention strategies to increase vaccination uptake in this high-risk group. The study was registered at the German Register of Clinical Studies (DRKS): https://drks.de/search/de/trial/DRKS00031559 (Registration Date: 28.08.2023).

BACKGROUND:Multiple sclerosis (MS) is the most common neuroimmunological disease in young adults. Data on its clinical onset before the age of 18 (paediatric-onset MS (POMS)) are limited. METHODS:This observational study present data on >1000 POMS compared with adult-onset MS (AOMS) and analysed patients regarding diagnostic delay, initial symptoms and long-term outcome using generalised additive models and adjustment for relevant confounders. RESULTS:The results showed a diagnostic delay and a higher proportion of women with POMS vs AOMS. Sensory (57%) and visual (48%) disturbances were the most common initial symptoms of POMS. Relapse rates were higher in POMS than in AOMS within the first 15 years after the clinical onset. The proportion of patients reaching an Expanded Disability Status Scale (EDSS) score of 3.0 by 15 years was lower in POMS (41%) than in AOMS (age-dependent, 48%-71%). A plateau phase in EDSS was observed in patients with POMS after age 40, which was not seen in those with AOMS. This plateau phase was responsible for the equalisation of the EDSS score with advanced age between POMS and AOMS. Cerebellar and polysymptomatic symptoms at clinical onset and male sex were predictors of higher EDSS scores in POMS, whereas in AOMS, pyramidal dysfunction was a predictor of worse outcomes. CONCLUSIONS:This largest and longest follow-up study of POMS to date revealed that women are more likely to develop MS at younger ages and experience different symptoms than men. Patients with POMS tend to have higher relapse rates but may recover more quickly from relapses and experience a more stable disease course later in life.

BACKGROUD:Uncertainty concerning motherhood is common among women with multiple sclerosis (wwMS). Therefore, we developed and pre-tested a patient decision aid (PtDA) and a nurse-led decision coaching intervention (DC) to support motherhood choice. The DC includes the PtDA, a decision guide on motherhood choice, and decision coaching. METHODS:We conducted a randomised pilot trial across Germany to test feasibility, with decisional conflict (Decisional Conflict Scale, DCS) as an exploratory endpoint. Initially, we planned a 3:1 randomisation ratio (planned; PtDA = 48, DC = 16). Due to recruitment difficulties, we switched to a 1:1 randomisation ratio to ensure an appropriate sample size (PtDA > 20, DC > 10). Women between 18 and 45 years old with relapsing-remitting MS or clinically isolated syndrome, and who had not yet decided about motherhood, were eligible. We recruited two nurses for our decision coaching training course. We used questionnaires to measure decisional conflict, programme feasibility, knowledge, and worries regarding pregnancy in MS. Interviews were conducted to gain in-depth information on the potential feasibility of the programmes. Interviews were analysed thematically and questionnaires descriptively. We conducted explorative group comparisons and merged findings using joint display analysis. RESULTS:We trained two decision coaches in the DC group and recruited 35 wwMS (PtDA = 22; DC = 13) over five months. Median DCS scores in the DC group were 49 at baseline and 15 at follow-up (range 0-100; higher scores indicate greater decisional conflict). In the PtDA group, scores were 54 (baseline) and 31 (follow-up). Explorative group comparison indicated lower decisional conflict at follow-up in the DC group than in the PtDA group (p = 0.035). Interviewees (PtDA = 5; DC = 6; nurses = 2) described both interventions as helpful for decision-making. Qualitative findings indicate greater satisfaction levels in the DC group. CONCLUSION:Both interventions appear useful for wwMS in making motherhood choices. The DC programme seems more promising in supporting decision-making. TRIAL REGISTRATION:German Clinical Trials Register (DRKS); DRKS00038534.

Introduction MINORE et SOPRANINO ont montré un transfert minimal de l’ocrélizumab dans le placenta et le lait maternel. Les données sur la première année de vie du nourrisson manquent. Objectifs Évaluer santé, croissance, développement, évolution des lymphocytes B (LB) et réponses aux vaccins à 1 an chez les nourrissons potentiellement exposés à ocrélizumab pendant la grossesse (MINORE) ou l’allaitement (SOPRANINO). Méthodes MINORE a inclus 35 femmes SEP enceintes avec dernière perfusion d’ocrélizumab 6 mois avant leurs dernières règles ou au cours du premier trimestre. SOPRANINO 13 femmes SEP allaitantes ayant reçu ocrélizumab entre 2 et 24 semaines après l’accouchement et leurs nourrissons. LB et réponses humorales des nourrissons ont été mesurés à l’âge de 13 mois, croissance et développement évalués aux mois 2, 4, 6, 9 et 12 et sécurité évaluée tout au long de l’étude. Résultats Les taux de LB des nourrissons sont restés dans les limites normales au 13e mois chez 95 % (20/21) des nourrissons MINORE et 100 % (11/11) des nourrissons SOPRANINO. Des réponses humorales séroprotectrices ont été détectées chez la plupart des nourrissons. Les événements indésirables étaient ceux généralement observés pendant la période. Les données complètes sur les réponses humorales et la croissance/le développement au cours de la première année de vie seront présentées. Discussion Les données MINORE et SOPRANINO montrent que la majorité des nourrissons potentiellement exposés à ocrélizumab pendant la grossesse ou l’allaitement ont présenté des réponses humorales aux vaccins infantiles, malgré la variabilité des taux de réponse. Conclusion Ces données élargissent les connaissances sur l’ocrélizumab dans le contexte de la planification familiale et fournissent une base factuelle pour la prise en charge clinique des femmes atteintes de SEP.

BACKGROUND:Women with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) and highly active disease may benefit from early post partum reinitiation of disease-modifying therapy (DMT), but safety data to monoclonal antibody (mAb) use while breastfeeding are limited. This study examined infant development and health following potential mAb exposure during breastfeeding. METHODS:A prospective monocentric cohort study of infants, born in 2013-2022, in the German MS and Pregnancy Registry, followed up 6-36 months post partum via telephone interviews. 183 infants breastfed during maternal mAb therapy (mAb use during breastfeeding (mAb-BF)) were matched 1:1 (DMT pregnancy exposure) to infants of DMT-naïve mothers (no-DMT-BF). Primary outcomes included developmental delay, systemic antibiotic use, hospitalisation, severe infection and growth. Adjusted regression models estimated the beta coefficient, OR or rate ratio with 95% CI. RESULTS:The study included 366 infants. Among 183 mAb-BF infants, most were breastfed on natalizumab (n=125), followed by ocrelizumab (n=34), rituximab (n=11) and ofatumumab (n=10); three had multiple exposures. Developmental delays occurred in 8.2% mAb-BF and in 7.1% no-DMT-BF infants (p=0.844). A comparable number of infants used a systemic antibiotic (n=33/183, 18.0% vs n=29/183, 15.8%; p=0.676), were hospitalised (n=18/183, 9.8% vs 19/183, 10.4%; p=1.000) or had a severe infection (n=14/183, 7.7% vs n=13/183, 7.1%; p=1.000). The physical growth and adjusted model outcomes were also similar. CONCLUSIONS:The results indicate that infants of mothers with neuroimmunological diseases, breastfed under mAbs, did not experience negative consequences for their development and health within the initial 6-36 months of life. This may encourage mothers with highly active disease to breastfeed.

Background: Bladder dysfunctions (BL-D) are common in people with multiple sclerosis (pwMS), significantly affecting daily life, infection risk, and survival. Nonetheless, BL-D are frequently stigmatized and inadequately addressed in clinical practice. To date, no comprehensive analysis of BL-D has been conducted in Germany. Objective: To assess the prevalence of BL-D and its subtypes in a German cohort and identify associated factors and treatment patterns. Methods: Data were analyzed from individuals enrolled in the German MS Register, aged ⩾18 with definite MS. Inclusion required ⩾3 visits and complete data on MS onset, diagnosis date, and BL-D status. BL-D were subclassified into urinary urgency, voiding dysfunction, bladder incontinence, and other BL-D. PwMS with different subtypes were compared regarding clinical, sociodemographic, and therapeutic characteristics and associated factors were identified using logistic regression. Results: The study cohort included 10,572 pwMS (71.7% female) with a mean age of 48.2 years, disease duration of 16.0 years, and median Expanded Disability Status Scale score of 2.0. BL-D was present in 38.0% of pwMS, with urinary urgency being the leading subtype (41.0%). Associations included older age, longer disease duration, progressive disease course, polysymptomatic onset, and receiving disease-modifying therapy. Interestingly, 37.1% of pwMS with BL-D received no bladder treatment, while 36.9% received pharmaceutical and 36.4% non-pharmaceutical bladder treatment. Conclusion: The results highlight the clinical relevance and burden of BL-D in MS and provide first insights into subtype-specific differences in the German MS population. Providing appropriate BL-D care requires investigation into causal factors and a deeper understanding of the underlying reasons of the treatment gap. Design: Retrospective, cross-sectional study.

BACKGROUND:Individuals with autoimmune or immune mediated diseases (AID) are more susceptible to infections and often experience worse outcomes if infected, underscoring the importance of vaccination. However, it remains unclear whether vaccine effectiveness (VE) differs between persons with and without AID. Our aim was to compare the effectiveness of influenza and herpes zoster vaccines in both groups, where the AID group consists of individuals with either multiple sclerosis (MS), chronic inflammatory bowel disease (IBD) or chronic inflammatory rheumatic disorders (CIRD). METHODS:We emulated five target trials using claims data from a large German health insurance provider: one for herpes zoster and four for influenza across different seasons. We used 1:1 balanced risk set matching and Cox proportional hazards models with interaction terms between vaccination status and AID status to estimate VE and differences in VE across groups. RESULTS:For the herpes zoster trial, 169,054 vaccinated individuals were matched to the same number of controls, including 10,994 AID individuals per group. Herpes zoster VE was 68.73 (95% CI 55.75-77.91) in the AID group and 60.30 (55.59-64.52) in the non-AID group (VE ratio: 1.14, 95% CI 0.93-1.30). Across four influenza seasons (2015/2016-2018/2019) between 1403,342 and 1713,064 individuals were included, including between 56,662 and 78,320 AID individuals. Influenza VE varied by outcome, season, and assumptions, but VE ratios remained near one in most analyses (VE ratios: -0.92-3.77), with all CIs including one. CONCLUSIONS:There was no evidence that VE differs meaningfully between individuals with and without AID, conditional on the included confounders. Both vaccines were similarly effective across groups, suggesting that VE is not reduced in MS, IBD, or CIRD patients. Further research is necessary to validate these findings for other AID and infections.

Women's neurology and obstetrics/gynecology experts convened to consolidate the best available evidence on multiple sclerosis (MS) management in reproductive-aged women, especially regarding the use of MS disease-modifying therapies (DMTs) surrounding pregnancy and lactation. To update 2014 clinical recommendations, an expert clinical review informed by a systematic literature search of PubMed, LactMed, and ClinicalTrials.gov was conducted utilizing keywords "multiple sclerosis" and "pregnancy." A total of 774 papers were screened for inclusion. To provide updated guidelines, two reviewers prioritized studies according to strength of evidence and relevance to validating/updating our clinical management recommendations. To provide updated information about pregnancy and lactation safety of available MS DMTs, an additional reviewer synthesized all available studies. All authors then reviewed data to craft consensus guidelines. We encourage collaborative care models to optimize symptom control, social support, and maternal wellbeing before, during, and after pregnancy. In most cases, MS is not associated with increased risks of adverse pregnancy outcomes, although some studies have reported slightly elevated risks of lower birthweight, preterm birth, and operative delivery. With appropriate monitoring, MS disease activity can often be minimized throughout the childbearing period by continuation or strategic timing of many DMTs to optimize maternal disease control while minimizing fetal risk. The postpartum period represents a period of increased medical and psychological risk, and close follow-up is recommended. After childbearing is complete, gynecological care can shift to prevention and management of gynecological complications (DMT-associated infections and risk of cervical dysplasia) and of the menopausal transition.

Prevalence of Multiple Sclerosis (MS) has increased over the last decades, primarily among women of childbearing age. Several algorithms for identifying MS have been described in the literature, providing heterogeneous prevalence estimates. We compared five algorithms to identify MS in women of childbearing age and estimated MS prevalence by time period and age-group. The study population included women aged 15 to 49 years-old between 2005 and 2019, from three data sources including all women (from Italy, Norway, and Wales), and three including pregnant women only (from France, Finland, and Spain; data collected around pregnancy). Five algorithms were tested: MS1 to MS3 combined MS diagnoses and MS-medicine prescriptions/dispensations, requiring 1, 2, or 3 occurrences, respectively; MS4 and MS5 used only MS diagnoses, requiring at least 2 occurrences (MS4 allowed just 1 if diagnosis was from inpatient care). In 2015–2019, MS prevalence based on MS1 ranged from 109 to 359 per 100,000 women: 109 in France, 121 in Spain, 195 in Wales, 232 in Finland, 264 in Italy, and 359 in Norway. More restrictive algorithms led to greater disparity, with MS3 ranging from 53 in Spain to 325 in Norway, and MS5 from 21 in France to 345 in Norway. All algorithms showed expected prevalence trends by time and age among women of childbearing age, though lower than in the literature. Overall, MS1 provided prevalence estimates most closely aligned with existing literature. This study offers key insights into choosing algorithms for identifying MS in women of childbearing age and in pregnant women.

BACKGROUND AND OBJECTIVES:With its use being contradicted during pregnancy, limited information exists concerning pregnancy and infant outcomes on exposure to cladribine tablets before or during pregnancy in women with multiple sclerosis (MS). In this study, we assess cumulative pregnancy exposure to cladribine tablets and prevalence of pregnancy and infant outcomes in women with MS exposed during pregnancy or within 6 months before conception and pregnancies fathered by men with MS exposed within 6 months before conception. METHODS:MAPLE-MS, a 10-year enhanced pharmacovigilance program, uses a global patient safety database to assess pregnancy outcomes potentially associated with cladribine tablets exposure in MS. Data collection began after the first approval of cladribine tablets (August 22, 2017). The primary outcome is the prevalence of major congenital anomalies (MCAs) in offspring. Secondary outcomes include other pregnancy outcomes (live birth, elective termination, spontaneous abortion, ectopic pregnancy, and stillbirth). RESULTS:In this Year 7 interim analysis, of 383 pregnancies analyzed, 336 (87.7%) involved maternal exposure to cladribine tablets and 47 (12.3%) were associated with paternal exposure. In the maternal exposure group, MCA prevalence (excluding genetic anomalies) in pregnancies with known outcomes was 1.1% (95% confidence interval [CI] 0.0-6.7; an atrial septal defect). Prevalence of live births in the maternal exposure group was 57.3% (95% CI 49.5-64.8). Secondary outcomes in the maternal exposure group were elective terminations (21.0% [95% CI 15.3-28.1]), spontaneous abortions (20.4% [95% CI 14.8-27.4]), and ectopic pregnancies (1.3% [95% CI 0.1-4.8]). In the paternal exposure group, no cases of MCA were observed in live births with known outcomes. Prevalence of live births was 81.3% (95% CI 56.2-94.2). Spontaneous abortions occurred in 12.5% (95% CI 2.2-37.3) and stillbirths in 6.3% (95% CI 0.0-30.3) of cases. DISCUSSION:Results are limited by the small number of pregnancies with known outcomes. Of pregnancies with known outcomes, the majority resulted in live births, with low frequencies of elective terminations and stillbirths reported. Since 2017, a single MCA (atrial septal defect) has been reported to the global patients' safety database. The results align with published estimates from the general population and MS patient cohorts.