by Sharon Roman[i]
Over the past 25-years, a wide range of injectable, oral or infusion-based disease modifying drugs (DMDs) have been approved to treat multiple sclerosis (MS). All were approved based on clinical trials which are typically short, lasting 2-3 years, and include a highly selected group of participants. Yet in routine clinical practice, DMDs are used in a much wider range of people who are expected to take them for many years.
Like many medications that affect the immune system, DMDs used to treat MS carry a risk of infections. In people with MS, the impact of infections over a lifetime can be considerable and infection risk exceeds those seen in the general population. Infections can also trigger MS relapses and disease activity. However, few studies published to date have evaluated the role of the MS DMDs on risk of infection. Despite a call for more studies related to co-existing conditions, and the lack of sex- and age-related data (age and sex can affect risk of adverse events and response to treatment), knowing the impact of these characteristics on DMD outcomes remains an unmet need. Here, the researchers examined if DMD use was associated with a change in infection-related healthcare use.
Using administrative healthcare data spanning the entire province of British Columbia, Canada, 19,360 people with MS (72% were women) were followed over a 21-year period. The researchers investigated whether DMD use (versus no use) was associated with changes in infection-related hospitalizations, doctors’ visits and prescriptions filled. They further explored whether any associations were affected by age (under 45 or 45 and older), sex, or specific co-existing conditions.
DMDs were grouped and assessed as any DMD, then by the way it was taken; by injection, as an infusion or orally. They included the injectables (beta-interferon, glatiramer acetate), infusions (natalizumab, alemtuzumab, daclizumab, and ocrelizumab) and orals (fingolimod, dimethyl fumarate, teriflunomide). Co-existing conditions which the researchers took into account as they could affect both infection risk and use of a DMD included 2 broad groups: any circulatory system disease and any mood/anxiety disorder or alcohol abuse, and 5 specific conditions: heart disease, high blood pressure, diabetes mellitus, diseases of the eye, and depression/anxiety
DMD use (versus none) associated with different infection-related healthcare use
Compared to no use of a DMD, the use of any DMD was associated with a 36% lower risk of infection-related hospitalizations and 12% lower rates of doctors’ visits, whereas infection-related prescriptions filled were 14% higher.
The way a DMD was taken affected results. Compared to no use of a DMD, the use of any injected or oral DMD was associated with lower infection-related doctors’ visits (injected DMDs by 12%, oral by 17%) and lower hospitalizations (injectable by 35%, oral by 46%), whereas use of any infusion DMD was not. While use of any injected DMD or DMD given by infusion was associated with a higher rate of infection-related prescriptions (injectable DMDs by 15%, infusions by 4%), oral DMDs were not.
For infection-related prescriptions filled, sex, but not age influenced findings. Women with MS who used a DMD (versus no use) had a higher rate of filling infection-related prescriptions. In women, use of any DMD (versus no use) was associated with an 18% higher rate of infection-related prescriptions filled, this was a significant difference from the 2% in men. Similarly, use of an injected DMD was associated with a 20% higher rate of infection-related prescriptions in women and 1% in men. The rate of prescriptions filled were similar whether a co-existing condition was present or not.
Real-world evidence of DMD use and infection risk
Few studies have assessed the relationship between DMD use and infections in those with MS. This population-based study spanning more than 20-years of healthcare use in 19,360 people with MS examined the relationship between DMD use and infection-related healthcare use (including prescriptions filled), and investigated the influence of age, sex, and co-existing conditions. While use of any DMD was not associated with an increased risk of infection-related hospitalizations or rate of doctors’ visits, infection-related prescriptions filled were higher. Moreover, both the way a DMD was taken and sex of the person with MS affected findings.
This is the largest, population-based study of its kind and provides real-world evidence of infection-related healthcare use and the DMDs to treat MS. It can help inform patient-doctor expectations surrounding infections and use of a DMD. How the differences identified in this study affect sex-based differences in healthcare and other health outcomes in people with MS deserves further investigation.
[i] Vancouver, BC, Canada
X: @SRoman_SPQR
Threads: @slhroman
Jonas Graf, Huah Shin Ng, Feng Zhu, Yinshan Zhao, José MA. Wijnands, Charity Evans, John D. Fisk, Ruth Ann Marrie, Helen Tremlett, Disease-modifying drugs, multiple sclerosis and infection-related healthcare use in British Columbia, Canada: a population-based study,The Lancet Regional Health – Americas, Volume 29, 2024, 10066, https://.doi.org/10.1016/j.lana.2023.100667
Tremlett's MS Research Explained 