1.
Short-term laboratory and related safety outcomes for the multiple sclerosis oral disease-modifying therapies: an observational study.
Kingwell, E, Zhang, T, Zhu, F, Walld, R, Carruthers, R, Evans, C, Marrie, RA, Tremlett, H
Expert opinion on drug safety. 2021;(4):481-487
Abstract
BACKGROUND Real-world safety data for the oral multiple sclerosis (MS) disease-modifying therapies (DMTs), dimethyl fumarate (DMF), fingolimod, and teriflunomide are important. We examined laboratory test abnormalities and adverse health conditions in new users. METHODS Linked laboratory and administrative health data were accessed for all persons with MS (PwMS) filling their first oral DMT prescription in two Canadian provinces. PwMS were followed from first prescription fill until discontinuation, death, emigration or study end. Proportions of PwMS, and incidence rates (IR)/100 person-years, were calculated for ≥1 event of elevated alanine aminotransferase (ALT) (>the upper limit of normal [ULN]; all DMTs), liver toxicity (ALT>3xULN; fingolimod); lymphopenia and proteinuria (DMF), and cardiac arrhythmia, hypertension and pneumonia (all DMTs). RESULTS Overall, 1,140 PwMS were followed for up to 2 years. De novo elevated alanine aminotransferase affected 13.2% (DMF), 12.4% (teriflunomide), and 30.0% (fingolimod) of users. Liver toxicity affected 2.8% of fingolimod, lymphopenia 3.1% of DMF, and proteinuria 2.9% of DMF users. The incidences of cardiac arrhythmia, pneumonia and hypertension ranged from <1 to 1.86/100 person-years depending on the DMT. CONCLUSIONS The short-term, real-world incidences of abnormal laboratory results or adverse events were consistent with the pivotal clinical trial findings. Longer-term safety data are still needed.
2.
Assessment of cancer risk with β-interferon treatment for multiple sclerosis.
Kingwell, E, Evans, C, Zhu, F, Oger, J, Hashimoto, S, Tremlett, H
Journal of neurology, neurosurgery, and psychiatry. 2014;(10):1096-102
Abstract
OBJECTIVE The risk of cancer after exposure to the β-interferons (IFNβs) for multiple sclerosis (MS) has not been established. We assessed whether IFNβ treatment for MS is associated with cancer risk or the risk of specific cancers in a population-based observational study. METHODS The British Columbia MS database was linked to the provincial Cancer Registry, Vital Statistics death files and Health Registration files. Using a nested case-control design, MS cancer cases were matched with up to 20 randomly selected MS controls at the date of cancer diagnosis by sex, age (± 5 years) and study entry year using incidence density sampling. Associations between treatment exposure and overall or specific (breast, colorectal, lung and prostate) cancers were estimated by conditional logistic regression, adjusted for MS disease duration and age. Tumour size at cancer diagnosis was compared between treated and untreated patients using the stratified Wilcoxon test to explore potential lead time bias. RESULTS The cohort included 5146 relapsing-onset MS patients and 48,705 person-years of follow-up, during which 227 cancers were diagnosed. Exposure to IFNβ was not significantly different for cases and controls (OR 1.28; 95% CI 0.87 to 1.88). There was a non-significant trend towards an increased risk of IFNβ exposure in the breast cancer cases (OR 1.77; 95% CI 0.92 to 3.42), but no evidence of a dose-response effect. Tumour size was similar between IFNβ treated and untreated cases. CONCLUSIONS There was no evidence of an increased cancer risk with exposure to IFNβ over a 12-year observation period. However, the trend towards an association between IFNβ and breast cancer should be investigated further.