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.

Pregnancy and reproductive health in women with multiple sclerosis: an update.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, neuro-degenerative disease of the central nervous system, prevalent in women of reproductive age. Today, many women want to start a family after MS diagnosis. There are over 20 treatments for MS, and safely navigating family planning is important. We review updated information on family planning, preconception, and peri-partum considerations, and reproductive concerns in special populations with MS. RECENT FINDINGS: There are no MS-related restrictions on any available and appropriate contraceptive method in women with MS. The question of MS and pregnancy outcomes following assisted reproduction, remains somewhat unsettled. In many studies, no elevated relapse risk is confirmed regardless of the type of fertility treatment. MRI status may offer better assessment of postpartum disease stability than relapse rate alone. Ongoing effective MS treatments during fertility assistance and before pregnancy, can further reduce the relapse risk. B-cell depleting therapies are emerging as safe and effective treatments for peripartum MS patients. SUMMARY: Patients with MS should receive accurate support and counseling related to their reproductive options. The general outlook on pregnancy and MS remains positive. The ever-increasing therapeutic complexity of MS calls for ongoing education and updated guidance for neuroimmunology and obstetrics healthcare providers.

Efficacy and Safety of Ponesimod Compared with Teriflunomide in Female Patients with Relapsing Multiple Sclerosis: Findings from the Pivotal OPTIMUM Study.

Background: Multiple sclerosis (MS) is threefold more prevalent in women than men. However, sex-specific efficacy analysis for MS disease-modifying therapies is not typically performed. Methods: Post hoc analyses of data from female patients enrolled in the phase 3, double-blind OPTIMUM study of relapsing MS were carried out. Eligible adults were randomized to ponesimod 20 mg or teriflunomide 14 mg once daily for up to 108 weeks. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included change in symptom domain of Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) at week 108, number of combined unique active lesions (CUALs) per year on magnetic resonance imaging, and time to 12- and 24-week confirmed disability accumulation (CDA). Results: A total of 735 female patients (581 of childbearing potential) were randomized to ponesimod (n = 363, 49.4%) or teriflunomide (n = 372, 50.6%). Relative risk reduction in the ARR for ponesimod versus teriflunomide was 33.1% (mean, 0.192 vs. 0.286, respectively; p < 0.002). Mean difference in FSIQ-RMS for ponesimod versus teriflunomide was -4.34 (0.12 vs. 4.46; p = 0.002); rate ratio in CUALs per year, 0.601 (1.45 vs. 2.41; p < 0.0001), and hazard ratio for time to 12- and 24-week CDA risk estimates, 0.83 (10.7% vs. 12.9%; p = 0.38) and 0.91 (8.8% vs. 9.7%; p = 0.69), respectively. Incidence of treatment-emergent adverse events was similar between treatment groups (89.0% and 90.1%). Conclusions: Analyses demonstrate the efficacy and safety of ponesimod, versus active comparator, for women with relapsing MS, supporting data-informed decision-making for women with MS. Clinical Trial Registration Number: NCT02425644.

Disparities by Race in Pregnancy Care and Clinical Outcomes in Women With Multiple Sclerosis: A Diverse Multicenter Cohort

BACKGROUND AND OBJECTIVES: Racial disparities exist in both neurologic and obstetric populations, underscoring the importance of evaluating pregnancy outcomes in diverse women with multiple sclerosis (MS). The objective of this multicenter retrospective study was to compare pregnancy care and outcomes between Black and Hispanic (underrepresented) and White women with MS. METHODS: Demographic and clinical data were extracted from medical records of 9 US MS centers for women with MS/clinically isolated syndrome who delivered live births between 2010 and 2021. Sites identified at last 15 consecutive Black/Hispanic women and a matching number of White women. Socioeconomic factors, pregnancy, and MS care/outcomes were compared between groups (underrepresented and White and then Black and Hispanic) using Wilcoxon rank sum (U statistic and effect size r reported), χ2, t tests and logistic regressions as appropriate to data type. Multiple imputation by chained equation was used to account for missing data. RESULTS: Overall, 294 pregnancies resulting in live births were analyzed ( 81 Black, 67 Hispanic, and 146 White mothers). Relative to underrepresented women, White women lived in areas of higher median (interquartile range [IQR]) Child Opportunity Index (79 [45.8] vs 22 [45.8], U = 3,824, r = 0.56, p < 0.0001) and were more often employed (84.9% vs 75%, odds ratio [OR] 2.57, CI 1.46-4.50, p = 0.0008) and privately insured (93.8% vs 56.8%, OR 11.6, CI 5.5-24.5, p < 0.0001) and more received a 14-week ultrasound (98.6% vs 93.9%, OR 4.66, CI 0.99-21.96, p = 0.027). Mode of delivery was significantly different between the three groups (X2(10,294) = 20.38, p = 0.03); notably, Black women had the highest rates of emergency cesarean deliveries, and Hispanic women highest rates of uncomplicated vaginal deliveries. Babies born to underrepresented women had lower median (IQR) birthweights than babies born to White women (3,198 g [435.3 g] vs 3,275 g [412.5 g], U = 9,255, r = 0.12, p = 0.04) and shorter median (IQR) breastfeeding duration (4.5 [3.3] vs 6.0 [4.2] months, U = 8,184, r = 0.21, p = 0.003). While underrepresented women were younger than White women (mean [SD] 30.9 [4.8] vs 33.8 [4.0], t = 1.97, CI 1.96-3.98, p < 0.0001), their median (Q1-Q3, IQR) Expanded Disability Status Scale was higher (1.5 [1-2.5, 1.5] vs 1 [0-1.5, 1.5], U = 7,260, r = 0.29, p < 0.0001) before pregnancy. Finally, medical records were missing more key data for Black women (19.7% missing vs 8.9% missing, OR 2.54, CI 1.25-5.06, p = 0.008). DISCUSSION: In this geographically diverse multicenter cohort, underrepresented women entered pregnancy with higher disability and fewer health care resources. Pregnancy represents a pivotal window where structural factors affect maternal and fetal health and neurologic trajectories; it is a critical period to optimize care and health outcomes.

Final analysis of 379 pregnancy outcomes after exposure to dimethyl fumarate in a prospective international registry.

BACKGROUND: Dimethyl fumarate (DMF) has a favorable benefit-risk profile treating people with multiple sclerosis and should be used in pregnant women only if the potential benefits outweigh potential risks to the fetus. OBJECTIVE: Assess pregnancy outcomes in a completed international registry (TecGistry) of women with MS exposed to DMF. METHODS: TecGistry included pregnant women with MS exposed to DMF, with data collected at enrollment, 6-7 months gestation, 4 weeks after estimated due date, and at postpartum weeks 4, 12, and 52. Outcomes included live births, gestational size, pregnancy loss, ectopic/molar pregnancies, birth defects, and infant/maternal death. RESULTS: Of 397 enrolled, median (range) age was 32 years (19-43). Median (range) gestational week at enrollment was 10 (0-39) and at first DMF exposure was 1 (0-13). Median (range) duration of gestational DMF exposure was 5 weeks (0-40). Fifteen (3.8%) spontaneous abortions occurred. Of 360 (89.1%) live births, 323 were full term and 37 were premature. One neonatal death and no maternal deaths occurred. Adjudicator-confirmed EUROCAT birth defects were found in 2.2%. CONCLUSION: DMF exposure during pregnancy did not adversely affect pregnancy outcomes; birth defects, preterm birth, and spontaneous abortion were in line with rates from the general population.

Inflammatory Activity After Diverse Fertility Treatments: A Multicenter Analysis in the Modern Multiple Sclerosis Treatment Era.

BACKGROUND AND OBJECTIVES: Patients with multiple sclerosis (MS) may seek fertility treatment (FT)-including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse. METHODS: Patients with clinically isolated syndrome (CIS) or MS aged 18-45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported. RESULTS: One hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25, p = 0.37), and the IRR was 0.95 (95% CI: 0.52-1.76, p = 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS, p = 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p = 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI. DISCUSSION: In this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

COVID-19 severity is associated with worsened neurological outcomes in multiple sclerosis and related disorders.

BACKGROUND: Neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 is not well understood. The objective of this study was to investigate neurologic outcomes in patients with MSRD post-COVID-19. METHODS: This was a retrospective medical records review study of adult patients with MSRD and COVID-19 infection at the Brigham MS Center. Neurologic worsening post-COVID-19 was defined as having a relapse, pseudorelapse, new brain MRI activity, worsening of preexisting MSRD symptoms, or development of other long-term neurologic symptoms. RESULTS: 111 patients, 85 (76.6%) females, with a mean [SD] age of 49.3 [12.2] years and median [range] EDSS of 2.5 [0, 8.5] were identified. 41 patients (36.9%) had neurologic worsening post-COVID-19. Of those, 19 (46.3%) had pseudorelapses, 2 (4.8%) had relapses, and 24 (58.5%) patients reported worsening of preexisting MSRD symptoms, or other new long-term neurologic symptoms. Neurologic worsening was associated with hospitalized (moderate or severe) COVID-19 (p = 0.001), treatment for COVID-19 (p = 0.006), and incomplete COVID-19 recovery (p = 0.0267) but not with age, sex, MS type, race, disease duration, EDSS, vitamin D use, or disease modifying therapy use. CONCLUSIONS: COVID-19 severity and lack of complete systemic recovery were associated with new or worsening neurologic symptoms in 36.9% of MSRD patients.

Pregnancy Management in Multiple Sclerosis and Other Demyelinating Diseases.

PURPOSE OF REVIEW: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs) are chronic autoimmune demyelinating conditions of the central nervous system often diagnosed in women of childbearing age. Therefore, safe family planning, pregnancy, and postpartum management are important considerations for many patients with MS or NMOSD. RECENT FINDINGS: Many patients with MS can safely become pregnant and remain well throughout pregnancy and the postpartum period with guidance from specialists on treatment planning. During pregnancy, women with NMOSD may face some increased risk of both neurologic and obstetric complications. Recent attention has focused on evaluating the safety of pharmacologic agents during pregnancy and breastfeeding. Unfortunately, care disparities remain common in both MS and NMOSD, and recovery of function is often not optimally managed in the postpartum period. SUMMARY: This article reviews the current state of knowledge on peripartum management in these neurologic conditions and offers practical considerations and case studies. When caring for women with MS and NMOSD of childbearing potential, treatment planning is important to optimize outcomes in both patient and newborn.

Risk factors for peripartum depression in women with multiple sclerosis.

BACKGROUND: Peripartum depression (PPD) is underexplored in multiple sclerosis (MS). OBJECTIVE: To evaluate prevalence of and risk factors for PPD in women with MS. METHODS: Retrospective single-center analysis of women with MS with a live birth. Prevalence of PPD was estimated with logistic regression with generalized estimating equations (GEE). GEE evaluated predictors of PPD (e.g. age, marital status, parity, pre-pregnancy depression/anxiety, antidepressant discontinuation, sleep disturbance, breastfeeding, relapses, gadolinium-enhancing lesions, and disability). Factors significant in univariable analyses were included in multivariable analysis. RESULTS: We identified 143 live births in 111 women (mean age 33.1 ± 4.7 years). PPD was found in 18/143 pregnancies (12.6%, 95% CI = 7.3-17.8). Factors associated with PPD included older age (OR 1.16, 95% CI = 1.03-1.32 for 1-year increase), primiparity (OR 4.02, CI = 1.14-14.23), pre-pregnancy depression (OR 3.70, CI = 1.27-10.01), sleep disturbance (OR 3.23, CI = 1.17-8.91), and breastfeeding difficulty (OR 3.58, CI = 1.27-10.08). Maternal age (OR 1.17, CI = 1.02-1.34), primiparity (OR 8.10, CI = 1.38-47.40), and pre-pregnancy depression (OR 3.89, CI = 1.04-14.60) remained significant in multivariable analyses. Relapses, MRI activity, and disability were not associated with PPD. CONCLUSION: The prevalence of PPD in MS appeared similar to the general population, but was likely underestimated due to lack of screening. PPD can affect MS self-management and offspring development, and prospective studies are needed.

COVID-19 mRNA vaccination leading to CNS inflammation: a case series.

The availability of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), provides hope towards mitigation of the coronavirus disease 2019 (COVID-19) pandemic. Vaccine safety and efficacy has not been established in individuals with chronic autoimmune diseases such as multiple sclerosis (MS). Anecdotal reports suggest that the vaccines may be associated with brain, spinal cord, peripheral nervous system, and cardiac inflammation. Based on the high morbidity and unpredictable course of COVID-19, and the need to achieve herd immunity, vaccination has been recommended for patients with MS. We report clinical and MRI features of seven individuals who received the Moderna (n = 3) or Pfizer (n = 4) SARS-CoV-2 mRNA vaccines. Within one to 21 days of either the first (n = 2) or second (n = 5) vaccine dose, these patients developed neurologic symptoms and MRI findings consistent with active CNS demyelination of the optic nerve, brain, and/or spinal cord. Symptoms included visual loss, dysmetria, gait instability, paresthesias, sphincter disturbance, and limb weakness. Age ranged from 24 to 64 (mean 39.1) years; five were woman (71.4%). The final diagnosis was exacerbation of known stable MS (n = 4, two were receiving disease-modifying therapy at the time of vaccination), new onset MS (n = 2), or new onset neuromyelitis optica (n = 1). All responded to corticosteroid (n = 7) or plasma exchange (n = 1) therapy, with five returning to baseline and two approaching baseline. Large prospective studies are required to further investigate any possible relationship between COVID-19 vaccines and acute CNS demyelination.

Interim Analysis of Pregnancy Outcomes After Exposure to Dimethyl Fumarate in a Prospective International Registry.

BACKGROUND AND OBJECTIVES: Oral delayed-release dimethyl fumarate (DMF) is not recommended during pregnancy and should only be used if the potential benefit justifies the potential fetal risk. Although DMF was well tolerated in clinical trials with consistent safety results in postmarketing surveillance, data are limited in pregnant women. The objective was to provide pregnancy outcomes and DMF exposure information from an interim analysis from a prospective, international registry (TecGistry; NCT01911767). METHODS: Women exposed to DMF from the first day of their last menstrual period before conception or during pregnancy were evaluated. Data were obtained at enrollment; 6-7 months' gestation; 4 weeks after estimated due date; and 4, 12, and 52 weeks after birth. Outcomes included live births, gestational size, pregnancy loss, birth defects, and infant or maternal death after delivery. Outcomes were analyzed cumulatively from October 30, 2013 (the start of TecGistry), to April 8, 2020. RESULTS: Of 345 enrolled patients, median (range) age was 32 (20-43) years. The mean (SD) duration of gestational weeks of DMF exposure was 4.9 (3.8). Most infants were full-term at birth (n = 249/274; 91%) and of average gestational size (n = 190/232; 82%). Of 351 outcomes, 277 were live births; 17 (5%) spontaneous abortions (95% confidence interval [CI] 2.6%-7.1%), including 1 (<1%) molar and 1 (<1%) ectopic pregnancy, were reported. There were 8 (2.9% [95% CI 1.3%-5.6%]) adjudicator-confirmed birth defects among the 277 live births. DISCUSSION: Interim results from this large registry indicate that early DMF exposure was not significantly associated with adverse pregnancy outcomes. Outcomes are consistent with previous smaller reports and with the general population. TRIAL REGISTRATION INFORMATION: TecGistry; clinical trial registration number: NCT01911767.

Clinical and Radiologic Disease Activity in Pregnancy and Postpartum in MS.

OBJECTIVE: To evaluate radiologic and clinical inflammatory activity in women with MS during pregnancy and postpartum. METHODS: We performed a retrospective analysis of prospectively collected clinical and MRI reports for women who became pregnant while followed at the University of California, San Francisco MS Center between 2005 and 2018. Proportion of brain MRIs with new T2-hyperintense or gadolinium enhancing (Gd+) lesions (primary outcome) and annualized relapse rate (ARR; secondary) were compared before and after pregnancy. RESULTS: We identified 155 pregnancies in 119 women (median Expanded Disability Status Scale [EDSS] 2.0). For the 146 live birth pregnancies, prepregnancy ARR was 0.33; ARR decreased during pregnancy, particularly the third trimester (ARR 0.10, p = 0.017) and increased in the 3 months postpartum (ARR 0.61, p = 0.012); and 16% of women experienced a clinically meaningful increase in EDSS. Among 70 pregnancies with paired brain MRIs available, 53% had new T2 and/or Gd+ lesions postpartum compared with 32% prepregnancy (p < 0.001). Postpartum clinical relapses were associated with Gd+ lesions (p < 0.001). However, even for patients without postpartum relapses, surveillance brain MRIs revealed new T2 and/or Gd+ lesions in 31%. Protective effects of exclusive breastfeeding for ≥3 months (odds ratio = 0.3, 95% confidence interval 0.1-0.9) were observed for relapses. CONCLUSIONS: Building on previous reports of increased relapse rate in the first 3 months postpartum, we report a significant association between inflammation on MRI and this clinical activity. We also detected postpartum radiologic activity in the absence of relapses. Both clinical and radiologic reassessment may inform optimal treatment decision-making during the high-risk early postpartum period.

Live birth rates, infertility diagnosis, and infertility treatment in women with and without multiple sclerosis: Data from an administrative claims database.

BACKGROUND: Real-world data regarding live birth rates (LBRs) and infertility in women with multiple sclerosis (MS) are lacking. This study compared LBRs, infertility diagnoses, and infertility treatments in women with and without MS. METHODS: Using a retrospective US administrative claims database, patients 18-55 years with MS were matched 1:1 to patients without MS to compare LBRs, infertility diagnoses, and infertility treatments used between cohorts. RESULTS: Overall LBRs were lower in women with MS (n=96,937) versus women without (n=96,937; 5.0% vs 7.0%; p<0.0001). A greater proportion of women with MS than without had a diagnosis of infertility (8.5% vs 8.1%; p=0.0006). Fewer women with MS than without used any infertility treatment (1.0% vs 1.2%; p=0.0002). Among women with or without MS who received infertility treatments, no significant difference was observed in LBRs with oral (32.2% vs 31.5%; p=0.8536) or injectable (44.0% vs 49.3%; p=0.2603) treatment. CONCLUSION: Women with MS had a lower LBR, received more infertility diagnoses, and were less likely to receive infertility treatment than women without MS. There was no difference in LBRs following infertility treatment. Claims-data studies provide valuable exploratory analyses that reflect interactions between patients and the healthcare system.

COVID-19 in teriflunomide-treated patients with multiple sclerosis.

The outbreak of a severe acute respiratory syndrome caused by a novel coronavirus (COVID-19), has raised health concerns for patients with multiple sclerosis (MS) who are commonly on long-term immunotherapies. Managing MS during the pandemic remains challenging with little published experience and no evidence-based guidelines. We present five teriflunomide-treated patients with MS who subsequently developed active COVID-19 infection. The patients continued teriflunomide therapy and had self-limiting infection, without relapse of their MS. These observations have implications for the management of MS in the setting of the COVID-19 pandemic.

Relapses and disease-modifying drug treatment in pregnancy and live birth in US women with MS.

OBJECTIVE: To evaluate relapse rates and disease-modifying drug (DMD) treatment in US women with multiple sclerosis (MS) and a live birth. METHODS: This retrospective administrative claims database study used US commercial health plan data from women with MS and a live birth from January 1, 2006, to June 30, 2015. Relapses and DMD treatment were evaluated 1-year prepregnancy, during pregnancy, during puerperium (6 weeks postpregnancy), and 1-year postpregnancy. Relapse was defined as MS-related hospitalization, emergency room visit, or outpatient visit with corticosteroid prescription within 7 days. Generalized estimating equation models for longitudinal data tested for differences between prepregnancy vs the other time periods. RESULTS: A total of 2,158 patients were eligible. The odds of relapse declined during pregnancy (odds ratio [OR] 0.623, 95% confidence interval [CI] 0.521-0.744; p < 0.0001), increased during puerperium (OR 1.710, 95% CI 1.358-2.152; p < 0.0001), and ended at a higher level during the last 3 postpartum quarters (OR 1.216, 95% CI 1.052-1.406; p = 0.0081). The proportion of women with DMD treatment was rather low overall: approximately 20% prepregnancy, bottoming to 1.9% during the second trimester, and peaking at 25.5% 9 to 12 months postpartum. DMD treatment declined significantly during pregnancy (OR 0.171, 95% CI 0.144-0.203; p < 0.0001), remained lower during puerperium (OR 0.361, 95% CI 0.312-0.418; p < 0.0001), and ended at a higher level during the last 3 postpartum quarters (OR 1.259, 95% CI 1.156-1.371; p < 0.0001). CONCLUSIONS: The rate of MS relapse decreased during pregnancy, increased 6 months postpartum, and decreased 6 to 12 months postpartum. DMD treatment was uncommon in the year before pregnancy, further decreased immediately prepregnancy and during pregnancy, and increased postpartum.

Pregnancy rates and outcomes in women with and without MS in the United States.

OBJECTIVE: To compare pregnancy prevalence and complications in women with and without multiple sclerosis (MS). METHODS: This retrospective US administrative claims study used data from January 1, 2006, to June 30, 2015. All data for women with MS were included. A nationally representative 5% random sample from approximately 58 million women without MS was used to compute the dataset. Annual pregnancy rates, identified via diagnosis/procedure codes and adjusted for covariates, were estimated via logistic regression. Claims for pregnancy and labor/delivery complications were compared using propensity score matching. RESULTS: From 2006 to 2014, the adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%; the adjusted proportion without MS and with pregnancy decreased from 8.83% to 7.75%. The difference in linear trend (0.17% increase and 0.15% decrease in per-annum pregnancy rates) was significant (t statistic = 7.8; p < 0.0001). After matching (n = 2,115 per group), a higher proportion of women with MS than without had claims for premature labor (31.4% vs 27.4%; p = 0.005), infection (13.3% vs 10.9%; p = 0.016), cardiovascular disease (3.0% vs 1.9%; p = 0.028), anemia/acquired coagulation disorders (2.5% vs 1.3%; p = 0.007), neurologic complications (1.6% vs 0.6%; p = 0.005), sexually transmitted diseases (0.4% vs 0.1%; p = 0.045), acquired fetal damage (27.8% vs 23.5%; p = 0.002), and congenital fetal malformations (13.2% vs 10.3%; p = 0.004). CONCLUSIONS: Pregnancy rates in this population of women with MS have been increasing. High rates of claims for several peripartum complications were observed in women with and those without MS. Claims data provide knowledge of interactions patients have with the health care system and are valuable initial exploratory analyses.

A case for gender-based approach to multiple sclerosis therapeutics.

Despite established sex differences in multiple sclerosis (MS) risk and course, sex-specific efficacy and toxicity of existing MS therapies, and possible sex-specific therapeutic approaches, remain underexplored. We systematically reviewed published sex differences from Phase III pivotal trials for FDA or EMA-approved MS disease modifying therapies (DMTs), along with additional information from pharmaceutical companies, for pre-specified or post-hoc baseline characteristics, efficacy and safety outcomes by sex, and sex-specific concerns. Then, we reviewed trials testing hormonal therapies in MS. None of the Phase III clinical trials performed baseline sex-specific analyses or were powered to evaluated DMTs in menopausal/older populations. Some recent trials performed pre-specified or post-hoc stratification of outcomes by sex. Sex-specific hormonal intervention trials were limited. Adequately powered, pre-specified analyses accounting for baseline sex and age are required to maximize safety and efficacy in specific patient populations.