Author Of 2 Presentations
P0388 - Safety of dimethyl fumarate for multiple sclerosis: A systematic review and meta-analysis (ID 255)
Abstract
Background
The safety profile of dimethyl fumarate (DMF) used in the treatment of multiple sclerosis (MS) is not fully understood.
Objectives
The objective of this study was to systematically review the literature for adverse events (AE) associated with DMF for MS.
Methods
We searched MEDLINE, EMBASE, CINAHL, Web of Science, CENTRAL, and clinicaltrials.gov for articles published from database inception to May/2019. Studies (observational and randomized controlled trials (RCTs)) reporting AEs, serious AEs (SAE), or discontinuation due to AEs were included. We summarized the proportion of DMF-exposed patients affected and calculated the risk ratios (RR) and number needed to treat for an additional harmful outcome (NNTH) and 95% confidence intervals (CI) for the DMF relative to placebo-exposed participants. RCT findings were pooled via meta-analyses.
Results
Twenty-one observational studies, 4 RCTs, 1 RCT extension study, and 2 open-label studies were included, totalling 12,380 MS patients on DMF followed for an average of 19.8 months. Compared to placebo, DMF-exposed patients had a higher risk of grade III/IV lymphopenia (NNTH=28.8;95%CI:20.2-50.5), pruritus (NNTH=22.1;95%CI:14.0-52.3), flushing (NNTH=3.7;95%CI:3.3-4.1), gastrointestinal related events (NNTH=5.7;95%CI:3.5-15.7), nausea (NNTH=23.4;95%CI:14.9-54.7), diarrhea (NNTH=21.2;95%CI:13.6-47.6), and abdominal pain (NNTH=19.2;95%CI:12.9-37.9). Patients discontinued DMF because of GI symptoms (498/5619;8.9%), lymphopenia (163/4003;4.1%), and flushing (173/4779;3.6%). From pooled analyses of 4 RCTs, AE risks were higher in the DMF versus placebo groups (RR=1.37;95%CI:1.27-1.48), but SAEs were similar (RR=1.01;95%CI:0.77-1.33).
Conclusions
Over the short-term, DMF was associated with a higher risk of AEs. The NNTH included 4 for flushing, 6 for gastrointestinal complaints, and 29 for severe or life-threatening (grade III/IV) lymphopenia. The longer-term safety of DMF, including consequences of lymphopenia remain unknown.
P0443 - Characteristics of a population exposed to a disease-modifying drug for multiple sclerosis in the real-world setting (1996-2017) (ID 200)
Abstract
Background
The efficacy of a disease-modifying drug (DMD) is typically established via brief clinical trials in highly selected groups. However, in clinical practice, DMDs are used for many years in a more diverse population of persons with multiple sclerosis (MS).
Objectives
The aim of the study was to describe the characteristics of a population with MS who are exposed to their first DMD in the real-world setting.
Methods
Using linked population-based health administrative data, we identified all individuals with MS aged ≥18 years who filled a prescription for a MS DMD in the province of British Columbia, Canada between 1996 and 2017. Individuals were followed from their first recorded demyelinating event to the earliest of death, emigration from the province, or study end (December 2017). We summarized cohort characteristics at their first filled DMD prescription (sex, age, socioeconomic status) and over the preceding year (comorbidity burden measured by the Charlson Comorbidity Index [CCI]).
Results
Overall, 4283 with MS filled a DMD prescription during the study period. Most were women (n=3132, 73%), with a mean (SD) age at the time of the first DMD prescription fill of 39.9 (9.9) years, and the socioeconomic status was distributed evenly across the income-based quintiles (neighborhood-level). Seventeen percent (n=741) had a CCI score ≥1. The most prevalent comorbidity was chronic pulmonary disease (n=235, 5%), followed by cerebrovascular disease (n=157, 4%) and diabetes (n=128, 3%). At the first DMD prescription fill, the proportion of women ranged from 63% (n=177/282) for dimethyl fumarate to 83% (n=15/18) for fingolimod. The mean (SD) age at first DMD prescription fill ranged from 37.2 (10.0) years for alemtuzumab to 43.0 (10.6) years for teriflunomide. Nearly 20% (n=724) were ≥50 years of age when they filled their first DMD prescription and 3% (n=108) were ≥60 years of age. From 1996-2012, the most common first DMD prescription filled was for either beta-interferon (n=2548/3190, 80%) or glatiramer acetate (n=612/3190, 19%). From 2013-2017, the most common first DMD prescription filled was for glatiramer acetate (n=379/1093, 35%), dimethyl fumarate (n=282/1093, 26%) or teriflunomide (n=182/1093, 17%).
Conclusions
Almost 1 in 5 persons with MS had at least some comorbidity at the time of initiation of their first DMD, while a minority were ≥60 years of age. As these individuals are often excluded from clinical trials, our data show an unmet need to understand the harms and benefits of DMD use in these understudied groups.
Presenter Of 1 Presentation
P0443 - Characteristics of a population exposed to a disease-modifying drug for multiple sclerosis in the real-world setting (1996-2017) (ID 200)
Abstract
Background
The efficacy of a disease-modifying drug (DMD) is typically established via brief clinical trials in highly selected groups. However, in clinical practice, DMDs are used for many years in a more diverse population of persons with multiple sclerosis (MS).
Objectives
The aim of the study was to describe the characteristics of a population with MS who are exposed to their first DMD in the real-world setting.
Methods
Using linked population-based health administrative data, we identified all individuals with MS aged ≥18 years who filled a prescription for a MS DMD in the province of British Columbia, Canada between 1996 and 2017. Individuals were followed from their first recorded demyelinating event to the earliest of death, emigration from the province, or study end (December 2017). We summarized cohort characteristics at their first filled DMD prescription (sex, age, socioeconomic status) and over the preceding year (comorbidity burden measured by the Charlson Comorbidity Index [CCI]).
Results
Overall, 4283 with MS filled a DMD prescription during the study period. Most were women (n=3132, 73%), with a mean (SD) age at the time of the first DMD prescription fill of 39.9 (9.9) years, and the socioeconomic status was distributed evenly across the income-based quintiles (neighborhood-level). Seventeen percent (n=741) had a CCI score ≥1. The most prevalent comorbidity was chronic pulmonary disease (n=235, 5%), followed by cerebrovascular disease (n=157, 4%) and diabetes (n=128, 3%). At the first DMD prescription fill, the proportion of women ranged from 63% (n=177/282) for dimethyl fumarate to 83% (n=15/18) for fingolimod. The mean (SD) age at first DMD prescription fill ranged from 37.2 (10.0) years for alemtuzumab to 43.0 (10.6) years for teriflunomide. Nearly 20% (n=724) were ≥50 years of age when they filled their first DMD prescription and 3% (n=108) were ≥60 years of age. From 1996-2012, the most common first DMD prescription filled was for either beta-interferon (n=2548/3190, 80%) or glatiramer acetate (n=612/3190, 19%). From 2013-2017, the most common first DMD prescription filled was for glatiramer acetate (n=379/1093, 35%), dimethyl fumarate (n=282/1093, 26%) or teriflunomide (n=182/1093, 17%).
Conclusions
Almost 1 in 5 persons with MS had at least some comorbidity at the time of initiation of their first DMD, while a minority were ≥60 years of age. As these individuals are often excluded from clinical trials, our data show an unmet need to understand the harms and benefits of DMD use in these understudied groups.