Importance Anti-CD20 biologics are widely used as disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), but recent reports have raised concerns about an increased risk of inflammatory bowel disease (IBD) during treatment. This study aimed to assess treatment-associated IBD risk in individuals with RRMS. Objective To compare the risk of new-onset IBD across different therapies for RRMS and relative to the general population. Design, Setting, and Participants This was a population-based cohort study conducted in Sweden. Through the Swedish MS register, initiations of rituximab, natalizumab, dimethyl fumarate, and fingolimod were identified between January 1, 2011, and December 31, 2023, in individuals with RRMS aged 18 to 55 years with at least 10 years of lookback time (5 years for dispensed drugs) and no evidence of previous IBD. These initiations were matched with general population comparator episodes selected from the Swedish population. Exposures Rituximab, comparator DMTs (natalizumab, dimethyl fumarate, fingolimod), or general population comparator. Main Outcomes and Measures New-onset IBD, defined as 2 or more records on separate dates with the International Statistical Classification of Diseases and Related Health Problems , Tenth Revision , codes K50 (Crohn disease), K51 (ulcerative colitis), and/or K52.3 (indeterminate colitis). Results Among the 13 748 therapy episodes (6481 rituximab, 2976 natalizumab, 2767 dimethyl fumarate, 1524 fingolimod) in 9251 individuals (range in mean ages of the exposure groups, 35-38 years) and 61 065 matched general population episodes, 164 IBD events occurred during follow-up (40 with rituximab, 4 with comparator DMTs, and 120 in the general population). The crude incidence rate of IBD was 110 (95% CI, 76-147) per 100 000 person-years for rituximab, 13 (95% CI, 3-30) for the comparator DMTs, and 41 (95% CI, 34-48) for the general population. After adjustment for demographics and MS characteristics, the hazard ratio for the comparator DMTs vs rituximab was 0.10 (95% CI, 0.04-0.22). In the rituximab group, 62% of IBD events were classified as Crohn disease compared with 29% in the general population. The number needed to harm for rituximab vs the comparator DMTs was 131 (95% CI, 93-228) at 5 years, after full adjustment. Conclusions and Relevance Results of this cohort study show that rituximab was associated with an increased risk of IBD compared with other modern MS therapies, after adjustment for differences in characteristics at therapy start. Clinicians and individuals with MS should consider IBD risk in treatment decisions and remain vigilant for gastrointestinal symptoms during anti-CD20 therapy.
This essay describes the author’s experience with severe postpartum anxiety and depression, suicidal ideation, and her time on an inpatient psychiatry unit.
Importance Late-onset epilepsy (LOE; onset at age ≥65 years) is increasingly recognized in older adults and may be associated with vascular risk. Objective To identify vascular risk factors (VRFs) associated with incident LOE in older adults. Design, Setting, and Participants This study is an individual participant data meta-analysis of 6 US population-based prospective cohort studies (the Epilepsy-Cog Study). In 5 cohorts linked to Medicare for epilepsy case ascertainment, follow-up for LOE began when a participant had accrued 2 years of continuous fee-for-service enrollment and was 65 years of age or older and extended to the end of continuous enrollment. Claims linkage covered 1991-2018 in the Atherosclerosis Risk in Communities Study (ARIC), 1992-2019 in the Cardiovascular Health Study (CHS), 2000-2019 in the Multi-Ethnic Study of Atherosclerosis (MESA), 2000-2020 in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS), and 1999-2019 in the Washington Heights/Inwood Columbia Aging Project (WHICAP). In the Northern Manhattan Study (NOMAS), which was not Medicare linked and used cohort-based epilepsy case ascertainment, follow-up for LOE began at cohort entry in 1993-2008 and extended to 2024. Data analysis was completed in January 2026. Exposures Sociodemographic characteristics and VRFs assessed by self-report, examinations, laboratory measures, and medication use. Main Outcome and Measures The primary outcome was incident LOE. Associations between risk factors and incident LOE were evaluated using multivariable Cox proportional hazards models to estimate hazard ratios. Results From 43 753 participants in Epilepsy-Cog, 551 participants with prevalent epilepsy and 945 with no follow-up after Epilepsy-Cog baseline were excluded. Among 42 257 participants (mean [SD] age, 71.4 [6.9] years; 23 383 [56.0%] female) followed up for a mean (SD) of 9.3 (6.2) years, 1500 participants (3.5%) developed LOE (3.8 per 1000 person-years). In fully adjusted models, LOE risk was higher with current smoking (HR = 1.39; 95% CI, 1.18-1.64), hypertension (HR = 1.17; 95% CI, 1.04-1.31), diabetes (HR = 1.42; 95% CI, 1.25-1.62), chronic kidney disease (HR = 1.29; 95% CI, 1.13-1.48), history of stroke (HR = 1.99; 95% CI, 1.63-2.43), and apolipoprotein E ε4 allele (1 ε4 allele: HR = 1.22; 95% CI, 1.07-1.39; 2 ε4 alleles: HR = 1.84; 95% CI, 1.36-2.50). Associations of VRFs with LOE were similar across age, sex, and race and ethnicity subgroups. Conclusions and Relevance In this pooled analysis of 6 US cohorts, multiple VRFs and a history of stroke were associated with incident LOE. These findings suggest that LOE may reflect the underlying burden of brain vascular disease.
Importance Global dementia incidence estimates are limited by underrepresentation of low- and middle-income countries and heterogeneous analytic methods. Due to these limitations, true understanding of the global dementia landscape remains incomplete. Objective To identify dementia incidence rates by age and sex in various regions worldwide (high-income countries and low- and middle-income countries) where data on clinically based dementia diagnoses were available. Data Sources Retrospective community-based cohorts from the Cohort Studies of Memory in an International Consortium (COSMIC); baseline recruitment commenced between January 1990 and December 2011 and follow-up data were collected through the end of 2021. Data were analyzed from June 2024 to June 2025. Study Selection Eligible studies included longitudinal COSMIC cohort studies with a clinically based diagnosis of dementia. Individual participant–level data from 22 population-based longitudinal cohorts (N = 38 418) spanning 18 countries or territories across 6 continents were included. Data Extraction and Synthesis Data extraction and assessment of study quality and validity were conducted according to Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Individual participant–level data were meta-analyzed in a 2-step process using random intercepts for country and study at the global and regional levels and by country income level. Main Outcomes and Measures For each study with a clinically based diagnosis, incidence rates for all-cause dementia were calculated and a 2-step meta-analysis was conducted. Using a person-years at risk framework with inverse-probability censoring weights and Poisson models, age- and sex-specific incidence were estimated and then standardized to the 2023 global age-sex population structure. Results Across 287 632 person-years at risk, 3001 participants developed dementia. Age- and sex-standardized incidence was 9.7 (95% CI, 7.89-11.97) per 1000 person-years at risk. Age-standardized incidence was higher in women than men (10.6; 95% CI, 8.61-13.11 vs 8.6; 95% CI, 6.94-10.72). Standardized incidence was higher in low- and middle-income countries (13.6; 95% CI, 9.67-19.24) than in high-income countries (8.3; 95% CI, 6.57-10.54). Applying age- and sex-specific rates to the projected 2050 population yielded a projected 24.7 million new cases, assuming constant incidence over time. Conclusions and Relevance The harmonized estimates presented in this study provide a comparable benchmark for global dementia incidence and inform planning for prevention, diagnosis, and memory-care services, particularly in underrepresented low- and middle-income country settings.
Importance Migraine affects individuals of reproductive age, but treatment options during pregnancy are limited due to safety concerns. Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are effective for migraine prevention; however, CGRP is important in placental development. Objective To determine whether early pregnancy exposure to anti-CGRP mAbs or propranolol is associated with spontaneous abortion compared with no exposure. Design, Setting, and Participants This retrospective cohort study used data from the AM-PREGNANT cohort, derived from the Merative MarketScan Commercial Database, from 2018 to 2021. Participants were followed up through 20 weeks’ gestation or until spontaneous abortion or censoring. Among 7 991 200 pregnancies identified in the AM-PREGNANT cohort, 7119 individuals contributing 7579 singleton pregnancies met the predefined eligibility criteria, including age 15 to 45 years, continuous insurance enrollment, last menstrual period (LMP) on or after November 1, 2018, pregnancy end or 20-week censoring by December 31, 2021, and pregestational migraine, defined as a migraine diagnosis or triptan or ergot prescription within 6 months before LMP. Data were analyzed in early 2026. Exposures Anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) or propranolol, defined as 1 or more filled prescription or injection procedure claim during follow-up and modeled as time-varying. Main Outcome and Measures Spontaneous abortion occurring at 20 weeks’ or less gestation. Multivariable Cox proportional hazards models adjusted for comorbidities and concomitant medications estimated the risk of spontaneous abortion. Results Among 7579 pregnancies in 7119 individuals (mean [SD] age, 31.6 [5.5] years), 1862 spontaneous abortions occurred. There were 100 spontaneous abortions (28.6%) during anti-CGRP mAb-exposed person-time, compared with 37 events among propranolol-exposed person-time without anti-CGRP mAbs (12.8%). Compared with unexposed individuals, anti-CGRP mAbs exposure was associated with an increased risk of spontaneous abortion (adjusted hazard ratio [aHR], 1.42; 95% CI, 1.12-1.80), which remained similar in bias-adjusted analyses (HR, 1.33; 95% simulation interval [SI], 1.23-1.45). Propranolol exposure was not associated with increased risk (aHR, 1.02; 95% CI, 0.71-1.47; bias-adjusted HR, 1.00; 95% SI, 0.96-1.03). Conclusion and Relevance In this study, early pregnancy exposure to anti-CGRP mAb was associated with a higher risk of spontaneous abortion, while no association was observed with propranolol. These findings support further evaluation of anti-CGRP mAb safety and emphasize counseling for individuals of childbearing potential.
