Evaluating the safety of β-interferons in MS

Abstract

Objective:To examine the association between interferon-β (IFN-β) and potential adverse events using population-based health administrative data in British Columbia, Canada.Methods:Patients with relapsing-remitting multiple sclerosis (RRMS) who were registered at a British Columbia Multiple Sclerosis Clinic (1995–2004) were eligible for inclusion and were followed up until death, absence from British Columbia, exposure to a non–IFN-β disease-modifying drug, or December 31, 2008. Incidence rates were estimated for each potential adverse event (selected a priori and defined with ICD-9/10 diagnosis codes from physician and hospital claims). A nested case-control study was conducted to assess the odds of previous IFN-β exposure for each potential adverse event with at least 30 cases. Cases were matched by age (±5 years), sex, and year of cohort entry, with up to 20 randomly selected (by incidence density sampling) controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated with conditional logistic regression adjusted for age at cohort entry.Results:Of the 2,485 eligible patients, 77.9% were women, and 1,031 were treated with IFN-β during follow-up. From the incidence analyses, 27 of the 47 potential adverse events had at least 30 cases. Patients with incident stroke (ORadj 1.83, 95% CI 1.16–2.89), migraine (ORadj 1.55, 95% CI 1.18–2.04), depression (ORadj 1.33, 95% CI 1.13–1.56), and hematologic abnormalities (ORadj 1.32, 95% CI 1.01–1.72) were more likely to have previous exposure to IFN-β than controls.Conclusions:Among patients with RRMS, IFN-β was associated with a 1.8- and 1.6-fold increase in the risk of stroke and migraine and 1.3-fold increases in depression and hematologic abnormalities.

Subcutaneous Interferon-β1a Does Not Increase the Risk of Stroke in Patients with Multiple Sclerosis: Analysis of Pooled Clinical Trials and Post-Marketing Surveillance

“…An increased risk of stroke with sc IFN-β1a was not observed during this study which was in contrast to a recent nested case–control analysis which used real-world data from a population-based health administrative database to show that IFN-β was associated with a 1.8-fold increase in the risk of stroke [22]. The study found that, of 2485 eligible RRMS patients, 1031 received IFN-β (all formulations; dose and trade name not specified) and patients with incident stroke were more likely to have previous exposure to IFN-β when compared with matched controls, with an adjusted odds ratio of 1.83 (95% CI 1.16, 2.89) [22].…”

“…The study found that, of 2485 eligible RRMS patients, 1031 received IFN-β (all formulations; dose and trade name not specified) and patients with incident stroke were more likely to have previous exposure to IFN-β when compared with matched controls, with an adjusted odds ratio of 1.83 (95% CI 1.16, 2.89) [22]. The mean age of the 2485 patients was 41.3 years and 77% were female; the mean follow-up was 8 years.…”

“…The nested case–control analysis included all potential adverse events (selected a priori after a comprehensive literature search and defined with International Classification of Diseases-9/-10 diagnosis codes from physician and hospital claims) in the treated patients involving at least 30 incident cases. For each case, up to 20 controls, matched by age, sex, and cohort entry year, were randomly selected from the population of patients at risk for the condition of interest [22]. The contrasting results between the nested case–control analysis and the present study may be explained in part by potential selection bias in controlled trials towards “healthier” patients through the use of pre-specified criteria to exclude patients with certain comorbidities or receiving certain co-medications.…”

“…Previous studies have shown contradictory results about the risk of stroke in patients treated with sc IFN-β1a over time. While one study reported an increased risk of stroke in patients with > 2 years IFN-β exposure [22], a population-based cohort study found an increased risk of overall stroke within the first year of MS diagnosis and attributed it to surveillance bias (e.g., an increased frequency of neuroimaging during the initial period after multiple sclerosis diagnosis) [16]. Two studies have reported a slight and persisting risk of overall stroke over the long term [6, 17].…”

“…They are widely prescribed and are generally well tolerated with a well-established, favorable safety profile [18–21]. However, to date, only one population-based study using health administrative data in British Columbia has evaluated the risk of stroke in patients treated with IFN-β (all formulations) [22]. …”