Comparison of disease modifying treatments in MS finds increased risk of infection in newer drugs

Dr. Helen Tremlett at the Djavad Mowafaghian Centre for Brain Health, 2018.

Over the past few years, Dr. Helen Tremlett and her team have been evaluating population health data to establish a greater understanding of the relationship between MS drug treatments, comorbidities, and associated health outcomes. Most recently, her team, including post-doctoral fellow Dr. José Wijnands, has undergone a first-of-its-kind study to assess disease modifying treatments (DMTs) for multiple sclerosis (MS) and their relationship with infection risk in the ‘real world’ clinical setting.

Looking at healthcare system usage and prescription data over nearly a decade, Dr. Tremlett’s team has looked far beyond the limited scope of a typical clinical trial to provide a panoramic picture of prescription and healthcare usage in British Columbia, Canada as it relates to the MS drug treatments and infection risk.

The team looked at anonymized health data on nearly 7,000 people with MS for an average of eight-and-a-half years. One in four had been exposed to a DMT. They found that exposure to a first-generation DMTs, specifically a beta-interferon or glatiramer acetate, was not associated with an increased risk of infection; conversely, exposure to a second-generation DMT, such as natalizumab, was associated with a 59 per cent increase in infection risk. Infection risk was measured as a physician visit which was coded, by the physician, as being primarily related to an infection.

The findings were published last week in the Journal of Neurology, Neurosurgery, & Psychiatry, building on work published last year with the same first author, former postdoctoral fellow Dr. José Wijnands. Last year’s research found that people who live with MS had more infection-related healthcare encounters than those who do not live with MS.

“This is the first study to look at infection risk over a long period, and to look beyond one specific drug or drug class,” said Dr. Helen Tremlett. “It’s a big-picture approach, as we’re able to look beyond the scope of a clinical trial to assess the real-world impacts of first- and second-generation DMTs over the long term.”

Interestingly, the first generation DMTs, specifically the beta-interferons, were associated with a reduced risk of upper respiratory infections such as pneumonia. This observation could be related to the beta-interferons’ known antiviral properties.

DMTs for MS are associated with a reduced risk of relapse, with modest benefits on disability outcomes. All the DMTs studied are licensed by Health Canada for use in MS. Reassuringly, the study authors could not find a significant association between DMT exposure and infection-related hospitalization, and the overall number of hospitalizations was low. Further work in this area is warranted, including what impact the DMT-associated infection burden, as measured in the current study, might have on patient outcomes.

Dr. Tremlett recently received funding from the Canadian Institutes of Health Research to assess the long-term safety and effectiveness of the MS DMTs across five Canadian provinces.

“By looking at these drugs and how they’re used in the real world, and by assessing a broad range of potential therapeutic benefits and adverse events, we intend to create clinically relevant, actionable evidence on the 10 or more existing drug treatments for MS” says Dr. Tremlett. “Ultimately, we hope that these findings will aid treatment-related decision-making in MS and improve health outcomes for people living with MS and their families.”

This study was funded by the National Multiple Sclerosis Society (RG5063A4/1, PI: Helen Tremlett, University of British Columbia). Dr. José Wijnands was funded by the Michael Smith Foundation for Health Research and The Koehle Family Foundation. Dr. Tremlett is the Canada Research Chair in Neuroepidemiology and Multiple Sclerosis.

Dr. Wijnands has completed her postdoctoral fellowship and is now conducting research with Dr. Martin McKeown and the Pacific Parkinson's Research Centre.

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citation

Wijnands JMA, Zhu F, Kingwell E, Fisk JD,  Evans C, Marrie RA, Zhao Y, Tremlett H. Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study. J Neurol Neurosurg Psychiatry. 2018 Mar 30. pii: jnnp-2017-317493. doi: 10.1136/jnnp-2017-317493. [Epub ahead of print]