The Antiretroviral Pregnancy Registry: Three decades of prospective monitoring for birth defects.

PURPOSE: Antiretrovirals (ARVs) are life-saving drugs used for the treatment and prevention of HIV infection and antiviral drugs (AVs) for the treatment of chronic HBV infection. ARVs have proven highly effective in reducing perinatal HIV transmission, however the risk of birth defects from prenatal exposure to ARVs/AVs is an ongoing concern. The Antiretroviral Pregnancy Registry (APR), an international, prospective exposure-registration cohort study, monitors ARV and AV use in pregnancy for early signals of teratogenicity. This communication reports results of 30-years' experience of ARV/AV exposure during pregnancy and lessons learned through continuous quality improvement. METHODS AND RESULTS: Birth defect prevalence is estimated and compared to internal and external groups. Statistical inference is based on exact methods for binomial proportions. Between 2006 and 2023, cumulative enrollment more than tripled from 6893 to 25 960 pregnancies and ARVs/AVs monitored increased from 29 to 222. Through January 2023, there were 21 636 live births and 631 outcomes with birth defects, for overall prevalence of 2.9/100 live births (95% CI 2.7, 3.2). The birth defect prevalence was 3.0% (95% CI 2.7%, 3.3%) among first trimester exposures and 2.8% (95% CI 2.5%, 3.2%) among second/third trimester exposures (prevalence ratio 1.04 [95% CI 0.89, 1.21]). CONCLUSIONS: Birth defect prevalence is not statistically significantly different between first trimester ARV/AV pregnancy exposures compared to second/third trimester exposures and is also not different from two population-based surveillance systems: 2.72/100 live births reported in the Metropolitan Atlanta Congenital Defects Program (MACDP); and 4.17/100 live births from the Texas Birth Defects Registry (TBDR).

Updated core competencies in pharmacoepidemiology to inform contemporary curricula and training for academia, government, and industry.

PURPOSE: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions. The aim of this project was to update the list of core competencies in pharmacoepidemiology. METHODS: To ensure applicability of findings to multiple areas, a working group was established consisting of ISPE members with positions in academia, industry, government, and other settings. All competencies outlined by Jones et al. were extracted from the initial manuscript and presented to the working group for review. Expert-based judgments were collated and used to identify consensus. It was noted that some competencies could contribute to multiple groups and could be directly or indirectly related to a group. RESULTS: Five core domains were proposed: (1) Epidemiology, (2) Clinical Pharmacology, (3) Regulatory Science, (4) Statistics and data science, and (5) Communication and other professional skills. In total, 55 individual competencies were proposed, of which 25 were new competencies. No competencies from the original work were dropped but aggregation or amendments were made where considered necessary. CONCLUSIONS: While many core competencies in pharmacoepidemiology have remained the same over the past 10 years, there have also been several updates to reflect new and emerging concepts in the field.

Belimumab use during pregnancy: Interim results of the belimumab pregnancy registry.

BACKGROUND: Belimumab is approved for active, autoantibody-positive systemic lupus erythematosus (SLE) and lupus nephritis, but limited data exist regarding its use in pregnancy. The Belimumab Pregnancy Registry (BPR, GSK Study BEL114256; NCT01532310) was created to evaluate pregnancy and infant outcomes following belimumab exposure. METHODS: Individuals with SLE exposed to belimumab from 4 months before and/or during pregnancy can enroll into the BPR. The primary outcome is major birth defects; secondary outcomes include miscarriages, stillbirths, elective termination, pre-term birth, neonatal death, small for gestational age, and adverse infant outcomes during the first year of life. Belimumab exposure timing, concomitant medications, and other potential confounding factors are also collected. Data up to March 8, 2021, are reported descriptively. RESULTS: From an expected sample size target of 500 prospective pregnancies with a known outcome, only 55 were enrolled in the study. Among these, two pregnancy losses and 53 pregnancies with a live birth outcome were reported. Ten of the 53 live birth pregnancies resulted in a major birth defect. Ten pregnancies were enrolled after the pregnancy outcome occurred and were examined retrospectively (four live births with no defects, four miscarriages, and two elective terminations). There was no indication or pattern of birth defects associated with belimumab. CONCLUSIONS: Low recruitment numbers for the BPR and incomplete information limit the conclusions regarding belimumab exposure during pregnancy. There was no pattern or common mechanism of birth defects associated with belimumab within the BPR data.

Belimumab use during pregnancy: a summary of birth defects and pregnancy loss from belimumab clinical trials, a pregnancy registry and postmarketing reports.

OBJECTIVE: Describe available data on birth defects and pregnancy loss in women with systemic lupus erythematosus (SLE) exposed to belimumab. METHODS: Data collected from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports up to 8 March 2020 were described. Belimumab exposure timing, concomitant medications and potential confounding factors were summarised descriptively. RESULTS: Among 319 pregnancies with known outcomes (excluding elective terminations), 223 ended in live births from which birth defects were identified in 4/72 (5.6%) in belimumab-exposed pregnancies and 0/9 placebo-exposed pregnancies across 18 clinical trials, 10/46 (21.7%) belimumab-exposed pregnancies in the BPR prospective cohort (enrolled prior to pregnancy outcome) and 0/4 belimumab-exposed pregnancies in the BPR retrospective cohort (enrolled after pregnancy outcome), and 1/92 (1.1%) in belimumab-exposed pregnancies from postmarketing/spontaneous reports. There was no consistent pattern of birth defects across datasets. Out of pregnancies with known outcomes (excluding elective terminations), pregnancy loss occurred in 31.8% (35/110) of belimumab-exposed women and 43.8% (7/16) of placebo-exposed women in clinical trials; 4.2% (2/48) of women in the BPR prospective cohort and 50% (4/8) in the BPR retrospective cohort; and 31.4% (43/137) of belimumab-exposed women from postmarketing/spontaneous reports. All belimumab-exposed women in clinical trials and the BPR received concomitant medications and had confounding factors and/or missing data. CONCLUSIONS: Observations reported here add to limited data published on pregnancy outcomes following belimumab exposure. Low numbers of exposed pregnancies, presence of confounding factors/other biases, and incomplete information preclude informed recommendations regarding risk of birth defects and pregnancy loss with belimumab use.

Building A Strong and Inclusive Workforce for Health: In Conversation with North Carolina Commerce Secretary Machelle Baker Sanders and Health Secretary Kody Kinsley.

North Carolina faces a significant health workforce shortage exacerbated by the COVID-19 pandemic. To meet this challenge, the Department of Commerce and the Department of Health and Human Services are prioritizing equity, creativity, and collaboration.

Building a Workforce for Health in North Carolina.

COVID-19 exposed and exacerbated the historical shortages and maldistribution of the health workforce in North Carolina. This edition of the North Carolina Medical Journal highlights the work being done in our state to address these needs, and calls for an intentional and persistent approach to planning for and developing the workforce needed to produce health.

A Prospective Cohort Study on Pregnancy Outcomes of Persons Immunized with a Seasonal Quadrivalent Inactivated Influenza Vaccine during Pregnancy.

This US-based, prospective observational cohort study evaluated the safety of a quadrivalent inactivated influenza vaccine (IIV4; Afluria Quadrivalent) in pregnant persons immunized over four influenza seasons between 2017 and 2021. Pregnancy outcomes included live birth, stillbirth, spontaneous abortion, and elective termination. Infant events of interest were major congenital malformations (MCMs), preterm birth (<37 weeks gestational age), and low birth weight (LBW). Data were descriptive; prevalence point estimates were reported with 95% confidence intervals (CI). A total of 483 pregnant persons were given IIV4 and evaluated; 477 (98.8%) reported a live birth, and there were 2 stillbirths, 4 spontaneous abortions, and no elective terminations or maternal deaths. The prevalence rates of infant events were as follows: preterm birth, 7.2% (upper 95% CI, 9.6%); LBW, 5.4% (upper 95% CI, 7.4%); and MCMs, 0.8% (upper 95% CI, 1.9%). Point estimates and upper 95% CIs of the observed prevalence rates were lower than or similar to background prevalence in the general US population. Our findings suggest no evidence of a safety concern with vaccinating this group at high risk of influenza complications and are consistent with published data from databases and surveillance systems that monitor the safety of influenza vaccines in pregnant persons.

Outcomes in Pregnant Persons Immunized with a Cell-Based Quadrivalent Inactivated Influenza Vaccine: A Prospective Observational Cohort Study.

Objective: To evaluate pregnancy and infant outcomes among persons immunized with a cell-based quadrivalent inactivated influenza vaccine (IIV4c) during routine pregnancy care. Design: Prospective observational cohort. Setting: US-based obstetrics/gynecology clinics. Population: Pregnant persons. This US-based, prospective observational cohort study evaluated the safety of quadrivalent inactivated influenza vaccine (IIV4c; Flucelvax® Quad) in pregnant persons immunized over 3 influenza seasons between 2017 and 2020. Pregnant persons were immunized with IIV4c as part of routine care, after which their health care provides HCPs with all observational data to a single coordinating center. Follow-up data were collected at the end of the second trimester and/or at the time of pregnancy outcome. A scientific advisory committee reviewed the data. Prevalence point estimates were reported with 95% confidence intervals (CIs). Pregnancy outcomes included: live birth, stillbirth, spontaneous abortion, elective termination, and maternal death. Infant outcomes included: preterm birth (<37 weeks gestational age), low birth weight (<2500 g), or major congenital malformations (MCMs). Of the 665 evaluable participants, 659 (99.1%) had a live birth. No stillbirths (0% [95% CI 0.0−0.6]), 4 spontaneous abortions (1.9% [0.5−4.8]), and 1 elective termination (0.5% [0.0−2.6]) were reported. Among 673 infants, 9.2% (upper 95% CI 11.5%) were born prematurely, 5.8% (upper 95% CI 7.6%) had low birth weight, and 1.9% (upper 95% CI 3.1%) were reported to have an MCM. No maternal deaths were reported. Of the 2 infants who died shortly after birth, one was adjudicated as not related to the vaccine; the other's cause could not be determined due to maternal loss to follow-up. The prevalence of adverse pregnancy outcomes or preterm birth, low birth weight, or MCMs in newborns was similar in persons vaccinated with IIV4c compared to the rates observed in US surveillance systems. The safety profile of IIV4c in pregnant persons is consistent with previously studied influenza vaccines.

Long-term safety and effectiveness of canakinumab therapy in patients with cryopyrin-associated periodic syndrome: results from the ß-Confident Registry.

OBJECTIVE: To report the long-term safety and effectiveness of canakinumab, a fully human anti-interleukin 1ß monoclonal antibody, in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID), in a real-world setting. METHODS: From December 2009 to December 2015, the ß-Confident Registry prospectively enrolled patients with CAPS and non-CAPS conditions who received canakinumab per routine care and were prospectively followed for up to 6 years. The registry protocol did not mandate specific visits or procedures; however, all observed adverse events (AEs) and serious adverse events (SAEs) had to be recorded. Canakinumab effectiveness was evaluated by Physician's Global Assessment (PGA). RESULTS: Of 288 patients enrolled, 3 were excluded due to missing informed consent. Among the remaining 285 patients, 243 (85.3%) were patients with CAPS and 42 (14.7%) had atypical CAPS (6.3%) or other conditions (8.4%). The median age was 26.6 years. Based on PGA, 58 of 123 (47.2%) patients with CAPS had no disease activity at 48 months, and 65 of 123 (52.8%) experienced mild/moderate disease activity at 48 months. Among CAPS phenotypes, AE incidence rates per 100 patient-years were lowest for FCAS (73.1; 95% CI 60.3 to 87.8) compared with those with MWS (105.0; 95% CI 97.2 to 113.2) or NOMID (104.6; 95% CI 86.6 to 125.2). One hundred twenty-eight SAEs were reported in 68 patients with CAPS (incidence rate/100 patient-years, 14.0; 95% CI 11.6 to 16.6). One death (metastatic rectal adenocarcinoma in a patient with MWS) was reported. CONCLUSIONS: The response to canakinumab was sustained for up to 6 years. Canakinumab demonstrated a favourable safety profile over long-term treatment in patients with CAPS. TRIAL REGISTRATION NUMBER: NCT01213641.

State Health Official Career Advancement and Sustainability Evaluation-Description of the Methods Used in the SHO-CASE Study.

State health officials (SHOs) lead state governmental public health agencies, playing an important role in their states. However, little comprehensive research has examined SHOs or characteristics of these leaders, limiting evidence about ways to improve SHO selection and subsequent performance. This brief describes the methods of the SHO-CASE study focused on current and former SHOs in state public health agencies. Methods used include qualitative components that informed the development of survey questions, survey administration, and survey response. A total of 147 SHOs responded to the SHO survey representing every state and Washington, District of Columbia. The SHO-CASE study survey database represents the most comprehensive database of its kind regarding a range of attributes of current and former SHOs. These data can be used to explore factors contributing to SHO success including valuable insights into effectively working with the states' elected officials.

Tenure and Turnover Among State Health Officials From the SHO-CASE Survey: Correlates and Consequences of Changing Leadership.

OBJECTIVE: To examine characteristics associated with tenure length of State Health Officials (SHOs) and examine reasons and consequences for SHO turnover. DESIGN: Surveys of current and former SHOs linked with secondary data from the United Health Foundation. SETTING: Original survey responses from SHOs in the United States. PARTICIPANTS: Respondents included SHOs who served between 1973 and 2017. MAIN OUTCOME MEASURES: Tenure length and consequences of SHO turnover. RESULTS: Average completed tenure among SHOs was 5.3 years (median = 4) and was shorter in recent time periods compared with decades prior. Older age at appointment (ß = -0.109, P = .005) and those holding a management degree (ß = -1.835, P = .017) and/or a law degree (ß = -3.553, P < .001) were each associated with shorter SHO tenures. State Health Officials from states in the top quartile for health rankings had significantly longer average tenures (ß = 1.717, P = .036). Many former SHOs believed that their tenure was too short and reported that their departure had either a significant or very large effect on their agency's ability to fulfill its mission. CONCLUSIONS: State Health Official tenures have become shorter over time and continue to be shorter than industry chief executive officers and best practice recommendations from organizational researchers. States have an opportunity to consider and address how factors within their control influence the stability of the SHO position.

Evaluation of pregnancy outcomes in patients with multiple sclerosis after fingolimod exposure.

BACKGROUND AND METHODS: Limited data are available on the safety of fingolimod in pregnant women. We estimated the risk of adverse pregnancy outcomes in women with multiple sclerosis (MS) exposed to fingolimod either shortly before or during pregnancy in prospectively collected cases from clinical trials, observational studies, surveillance programs, and spontaneous reports. RESULTS: The prevalence of major malformations among live births does not appear to be significantly higher than those in the general population and the unexposed MS population. Similarly, the prevalence of cardiac malformations observed in this analysis was not significantly different from that of the general population. Proportions of miscarriage were in line with those of the general and unexposed MS population and no specific pattern of birth defects was identified. CONCLUSIONS: These data can help inform healthcare professionals and women with MS exposed to fingolimod during conception.

High Turnover Among State Health Officials/Public Health Directors: Implications for the Public's Health.

CONTEXT: State health officials (SHOs) serve a critical role as the leaders of state public health systems. Despite their many responsibilities, there is no formal process for preparation to become an SHO, and few requirements influence the selection of an SHO. Furthermore, to date, no studies have examined SHO tenure or their experiences. OBJECTIVE: This study examines SHO tenure over time and the relationship between SHO tenure and organizational and state attributes. DESIGN: This longitudinal study employed primary data on SHOs and secondary data from the Association of State and Territorial Health Officials on organizational attributes of state public health agencies. SETTING: This study examines SHOs within the United States. PARTICIPANTS: SHOs who served in years 1980-2017. MAIN OUTCOME MEASURES: Annual average SHO tenure; average SHO tenure by state. RESULTS: In the 38 years of this study, 508 individuals served as SHOs in the 50 states and the District of Columbia. The average tenure over this period was 4.1 years, with a median tenure of 2.9 years. During the study period, almost 20% of SHOs served terms of 1 year or less. A total of 32 SHOs (32/508 or 6.3%) served for 10 years or longer. Excluding SHOs who served 10 years or longer (n = 32 SHOs who had a collective 478 years of tenure) reduces the average term in office to 3.5 years. The average number of new SHOs per year is 12.3. SHOs appointed by a board of health averaged more than 8 years in office compared with averages just under 4 years for those appointed by governors or secretaries of state agencies. CONCLUSIONS: There are notable differences in SHO tenure across states. Future research is needed to further examine SHO tenure, effectiveness, job satisfaction, transitions, and the relationship between SHOs and state health. It may be valuable to expand on opportunities for new SHOs to learn from peers who have moderate to long tenures as well as SHO alumni. Given that average SHO tenure is approximately 4 years and that an SHO could be thrust into the national spotlight at a moment's notice, governors may want to consider experience over partisanship as they appoint new SHOs.

Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study.

Objectives: Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. Methods: All CAPS patients followed in the ß-CONFIDENT (Clinical Outcomes and Safety Registry study of Ilaris patients) registry were analysed if they had received a vaccination. The ß-CONFIDENT registry is a global, long-term, prospective, observational registry, capturing and monitoring patients treated with canakinumab. Results: Sixty-eight CAPS patients had received a total of 159 vaccine injections, 107 injections against influenza, 19 pneumococcal vaccinations, 12 against tetanus/diphtheria antigens and 21 other vaccinations. Fourteen per cent of injections had elicited at least one vaccine reaction. All five vaccine-related serious adverse events were associated with pneumococcal vaccination. Vaccine reactions were observed in 70% of pneumococcal vaccinations, compared with 7% in influenza and 17% in tetanus/diphtheria vaccinations. The odds ratios to react to the pneumococcal vaccines compared with influenza and tetanus/diphtheria vaccines were 31.0 (95% CI: 8, 119) and 10.8 (95% CI: 2, 74). Vaccine reactions after pneumococcal vaccinations were more severe and lasted significantly longer (up to 3 weeks) compared with other vaccinations. In two patients, pneumococcal vaccination also elicited symptoms consistent with systemic inflammation due to CAPS reactivation. Conclusion: Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients.

Recommendations for selecting drug-drug interactions for clinical decision support.

PURPOSE: Recommendations for including drug-drug interactions (DDIs) in clinical decision support (CDS) are presented. SUMMARY: A conference series was conducted to improve CDS for DDIs. A work group consisting of 20 experts in pharmacology, drug information, and CDS from academia, government agencies, health information vendors, and healthcare organizations was convened to address (1) the process to use for developing and maintaining a standard set of DDIs, (2) the information that should be included in a knowledge base of standard DDIs, (3) whether a list of contraindicated drug pairs can or should be established, and (4) how to more intelligently filter DDI alerts. We recommend a transparent, systematic, and evidence-driven process with graded recommendations by a consensus panel of experts and oversight by a national organization. We outline key DDI information needed to help guide clinician decision-making. We recommend judicious classification of DDIs as contraindicated and more research to identify methods to safely reduce repetitive and less-relevant alerts. CONCLUSION: An expert panel with a centralized organizer or convener should be established to develop and maintain a standard set of DDIs for CDS in the United States. The process should be evidence driven, transparent, and systematic, with feedback from multiple stakeholders for continuous improvement. The scope of the expert panel's work should be carefully managed to ensure that the process is sustainable. Support for research to improve DDI alerting in the future is also needed. Adoption of these steps may lead to consistent and clinically relevant content for interruptive DDIs, thus reducing alert fatigue and improving patient safety.

Prenatal exposure to zidovudine and risk for ventricular septal defects and congenital heart defects: data from the Antiretroviral Pregnancy Registry.

OBJECTIVE: To assess the risk for ventricular septal defects and congenital heart defects following zidovudine exposure during pregnancy using data from the Antiretroviral Pregnancy Registry. STUDY DESIGN: Data on 16,304 prospectively reported pregnancies were analyzed to estimate the frequency and risk of ventricular septal defects and congenital heart defects, comparing exposure between zidovudine-containing regimens and non-zidovudine antiretroviral regimens. The numerator includes defect cases in outcomes at ≥ 20 weeks of gestational age. The denominator includes live birth outcomes. Infants with chromosomal anomalies were excluded. RESULTS: There were 15,451 live birth outcomes; 13,073 were prenatally exposed to zidovudine-containing regimens and 2378 to non-zidovudine containing regimens. There were 36 ventricular septal defect cases: 31 exposed to prenatal zidovudine and 5 unexposed. Nine of the zidovudine-exposed cases had earliest exposure in the first trimester; 22 had second/third trimester exposure. Of the 5 ventricular septal defect cases not exposed to zidovudine, 2 had earliest exposure to non-zidovudine antiretroviral regimens in the first trimester, and 3 had exposure in the second/third trimester. The prevalence of ventricular septal defect was 0.24% (95% confidence interval: 0.16, 0.34) for infants exposed to zidovudine-containing regimens and 0.21% (95% confidence interval: 0.07, 0.49) for non-zidovudine regimens. The relative risk comparing the 2 was 1.13 (95% confidence interval: 0.44, 2.90). There were a total of 90 congenital heart defect cases; 78 were exposed prenatally to zidovudine-containing regimens, and 12 were unexposed. Twenty-six of the zidovudine-exposed cases had earliest exposure in the first trimester and 52 had second/third trimester exposure. Six congenital heart defect cases with non-zidovudine antiretroviral regimens had earliest exposure in the first trimester and 6 had exposure in the second/third trimester. The prevalence of congenital heart defects was 0.60% (95% confidence interval: 0.47, 0.74) for infants exposed to zidovudine-containing regimens and 0.50% (95% confidence interval: 0.26, 0.88) for non-zidovudine regimens. The relative risk comparing the 2 was 1.18 (95% confidence interval: 0.64, 2.17). CONCLUSIONS: The prevalence and risk of ventricular septal defects and congenital heart defects among infants exposed to zidovudine-containing regimens is not significantly different from the prevalence and risk in infants exposed to non-zidovudine containing regimens. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01137981.

Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: An observational study using the US Department of Defense administrative claims database.

BACKGROUND: Data are limited for mortality and comorbidities in patients with multiple sclerosis (MS). OBJECTIVES: Compare mortality rates and event rates for comorbidities in MS (n=15,684) and non-MS (n=78,420) cohorts from the US Department of Defense (DoD) database. METHODS: Comorbidities and all-cause mortality were assessed using the database. Causes of death (CoDs) were assessed through linkage with the National Death Index. Cohorts were compared using mortality (MRR) and event (ERR) rate ratios. RESULTS: All-cause mortality was 2.9-fold higher in the MS versus non-MS cohort (MRR, 95% confidence interval [CI]: 2.9, 2.7-3.2). Frequent CoDs in the MS versus non-MS cohort were infectious diseases (6.2, 4.2-9.4), diseases of the nervous (5.8, 3.7-9.0), respiratory (5.0, 3.9-6.4) and circulatory (2.1, 1.7-2.7) systems and suicide (2.6, 1.3-5.2). Comorbidities including sepsis (ERR, 95% CI: 5.7, 5.1-6.3), ischemic stroke (3.8, 3.5-4.2), attempted suicide (2.4, 1.3-4.5) and ulcerative colitis (2.0, 1.7-2.3), were higher in the MS versus non-MS cohort. The rate of cancers was also higher in the MS versus the non-MS cohort, including lymphoproliferative disorders (2.2, 1.9-2.6) and melanoma (1.7, 1.4-2.0). CONCLUSIONS: Rates of mortality and several comorbidities are higher in the MS versus non-MS cohort. Early recognition and management of comorbidities may reduce premature mortality and improve quality of life in patients with MS.