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Research paper
Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study
  1. José Maria Andreas Wijnands1,
  2. Feng Zhu1,
  3. Elaine Kingwell1,
  4. John David Fisk2,
  5. Charity Evans3,
  6. Ruth Ann Marrie4,5,
  7. Yinshan Zhao1,
  8. Helen Tremlett1
  1. 1 Department of Medicine (Neurology), University of British Columbia, Vancouver, Canada
  2. 2 Departments of Psychiatry, Medicine, and Psychology and Neuroscience, Dalhousie University, Halifax, Canada
  3. 3 College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada
  4. 4 Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
  5. 5 Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada
  1. Correspondence to Dr Helen Tremlett, Medicine (Neurology), University of British Columbia, Vancouver V6T 2B5, Canada; helen.tremlett{at}


Objective Little is known about disease-modifying treatments (DMTs) for multiple sclerosis (MS) and infection risk in clinical practice. We examined the association between DMTs and infection-related medical encounters.

Methods Using population-based administrative data from British Columbia, Canada, we identified MS cases and followed them from their first demyelinating event (1996–2013) until emigration, death or study end (December 2013). Associations between DMT exposure (by DMT generation or class) and infection-related physician or hospital claims were assessed using recurrent time-to-events models, adjusted for age, sex, socioeconomic status, index year and comorbidity count. Results were reported as adjusted HRs (aHRs).

Results Of 6793 MS cases, followed for 8.5 years (mean), 1716 (25.3%) were DMT exposed. Relative to no DMT, exposure to any first-generation DMT (beta-interferon or glatiramer acetate) was not associated with infection-related physician claims (aHR: 0.96; 95% CI 0.89 to 1.02), nor was exposure to these drug classes when assessed separately. Exposure to any second-generation DMT (oral DMT or natalizumab) was associated with an increased hazard of an infection-related physician claim (aHR: 1.47; 95% CI 1.16 to 1.85); when assessed individually, the association was significant for natalizumab (aHR: 1.59; 95% CI 1.19 to 2.11) but not the oral DMTs (aHR: 1.17; 95% CI 0.88 to 1.56). While no DMTs were associated with infection-related hospital claims, these hospitalisations were also uncommon.

Conclusion Exposure to first-generation DMTs was not associated with an altered infection risk. However, exposure to the second-generation DMTs was, with natalizumab associated with a 59% increased risk of an infection-related physician claim. Continued pharmacovigilance is warranted, including an investigation of the DMT-associated infection burden on patient outcomes.

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  • Contributors The corresponding author HT takes responsibility for the integrity of the data and the accuracy of the data analysis. The analyst JW and principal investigator HT had full access to the data. All authors contributed to the interpretation of the data. JW drafted the manuscript. All authors revised the manuscript and approved the final version to be published.

  • Funding This study was supported by the National Multiple Sclerosis Society (RG5063A4/1). The funding source had no involvement in the study design, the collection, analysis and interpretation of the data or in the decision to submit this article for publication.

  • Disclaimer All inferences, opinions and conclusions drawn in this publication are those of the authors, and do not reflect the opinions or policies of the data steward(s).

  • Competing interests FZ, EK and YZ report no disclosures. JMAW receives research funding from the Michael Smith Foundation for Health Research/The Koehle Family Foundation. CE receives research funding from the Canadian Institutes of Health Research, Saskatchewan Health Research Foundation and the Multiple Sclerosis Society of Canada. JDF receives research funding from the Canadian Institutes of Health Research, Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society and the Dalhousie Medical Research Foundation, consultation and distribution royalties from MAPI Research Trust, as well as speaker honoraria and travel expenses from EMD Serono (2013 and 2014). RAM receives research funding from the Canadian Institutes of Health Research, Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, Research Manitoba, the Consortium of MS Centers, Crohn’s and Colitis Canada and the Waugh Family Chair in Multiple Sclerosis and has conducted clinical trials funded by Sanofi-Aventis. HT is the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis. She has received research funding from the Multiple Sclerosis Society of Canada, the Michael Smith Foundation for Health Research Scholar, the National Multiple Sclerosis Society, the Canadian Institutes of Health Research and the UK MS Trust; speaker honoraria and/or travel expenses to attend conferences from the Consortium of MS Centres (2013), the National MS Society (2012, 2014, 2015 and 2016), Bayer Pharmaceuticals (2010), Teva Pharmaceuticals (2011), ECTRIMS (2011, 2012, 2013, 2014 and 2015), UK MS Trust (2011), the Chesapeake Health Education Program, US Veterans Affairs (2012), Novartis Canada (2012), Biogen Idec (2014) and American Academy of Neurology (2013, 2014, 2015 and 2016). Unless otherwise stated, all speaker honoraria are either declined or donated to an MS charity or used as an unrestricted grant for use by her research group.

  • Ethics approval The study was approved by the University of British Columbia’s Clinical Research Ethics Board (#H14-00448) and the provincial health agencies regulating the use of administrative data.

  • Provenance and peer review Not commissioned; externally peer reviewed.