COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies.

BACKGROUND: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS). OBJECTIVE: The objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies. METHODS: The IBM® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database. RESULTS: 30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine. CONCLUSIONS: Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.

Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden.

BACKGROUND: Our aim was to estimate and compare the prevalence of adverse pregnancy outcomes among pregnant women with multiple sclerosis (MS) exposed to interferon beta (IFNB) and among women with MS unexposed to any MS disease-modifying drug (MSDMD). METHODS: This cohort study used Finnish (1996-2014) and Swedish (2005-2014) national register data. Women with MS having IFNB dispensed 6 months before or during pregnancy as the only medication were considered as IFNB exposed (only IFNB-exposed), whereas women with MS unexposed to any MSDMD were considered unexposed (MSDMD-unexposed). Prevalence was described and compared using log-binomial or logistic regression and adjusted for potential confounders including maternal age and comorbidity. RESULTS: Among 2831 pregnancies, 2.2% of the only IFNB-exposed and 4.0% of the MSDMD-unexposed women had serious adverse pregnancy outcomes [elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA) in live, or stillbirth]. After adjustments, the prevalence of serious adverse pregnancy outcomes was lower among the only IFNB-exposed compared with the MSDMD-unexposed [relative risk 0.55, 95% confidence interval (CI) 0.31-0.96]. The prevalence of individual outcomes, including MCA, spontaneous abortions, and stillbirths was not increased with IFNB exposure. Women with MS exposed to IFNB appeared more likely to terminate their pregnancy for reasons other than foetal anomaly, compared with MSDMD-unexposed pregnant MS patients (odds ratio 1.71, 95% CI 1.06-2.78). CONCLUSION: In this large cohort study, no increase in the prevalence of adverse pregnancy outcomes was observed in women with MS exposed to IFNB compared with MS patients unexposed to any MSDMDs. This study together with other evidence led to a change in the labels of the IFNB products in September 2019 in the European Union, and IFNB use today may be considered during pregnancy, if clinically needed.

Pregnancy outcomes in interferon-beta-exposed patients with multiple sclerosis: results from the European Interferon-beta Pregnancy Registry.

BACKGROUND: Family planning is an important consideration for women with multiple sclerosis (MS), who are often diagnosed during their reproductive years. Currently, limited data are available on pregnancy outcomes in patients exposed to interferon-beta (IFN-beta) before or during pregnancy. Here, we present the cumulative pregnancy exposure data and prevalence of pregnancy and infant outcomes in IFN-beta-exposed pregnant women with MS from the European IFN-beta Pregnancy Registry. METHODS: Using spontaneous and solicited reports, the registry collected data from 26 countries of the European Economic Area, consisting of information on women with MS identifying themselves to one of the Marketing Authorisation Holders (Bayer, Biogen, Merck KGaA, and Novartis) or healthcare professionals as pregnant and exposed to IFN-beta during pregnancy or within 1 month before conception. The outcomes collected by the registry included ectopic pregnancies, spontaneous abortions, elective terminations, live, and stillbirths with or without congenital anomalies. The prevalence of pregnancy outcomes was put in context with those reported in the general population. RESULTS: Between 2009 and 2017, the registry collected 948 pregnancy reports with a known pregnancy outcome. Overall, 82.0% (777/948) of pregnancies resulted in live birth without congenital anomaly. When comparing IFN-beta-exposed pregnancies with the general population, the prevalence of spontaneous abortions (10.7% vs. 10-21%) and congenital anomalies in live births (2.1% vs. 2.1-4.1%) were found to be within reported ranges. CONCLUSIONS: The data gathered from these pregnancy cases suggest no evidence that IFN-beta exposure before conception and/or during pregnancy adversely increases the rate of congenital anomalies or spontaneous abortions.

The association between exposure to interferon-beta during pregnancy and birth measurements in offspring of women with multiple sclerosis.

BACKGROUND: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted. OBJECTIVES: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs. METHODS: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005-2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy. RESULTS: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed. CONCLUSIONS: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference.