Relapse comparable among common DMTs for MS

Dimethyl fumarate and fingolimod appeared to have no significant difference in relapse rates, and rituximab appeared to have better relapse outcomes than natalizumab in patients with MS, according to results published in JAMA Network Open.

“The [MS] treatment landscape has changed considerably because of the growing number of approved disease-modifying therapies (DMTs),” Jue Hou, PhD, of the department of biostatistics at Harvard T.H. Chan School of Public Health in Boston, and colleagues wrote. “Standard-efficacy DMTs (eg, dimethyl fumarate and fingolimod) and higher-efficacy DMTs (eg, natalizumab and rituximab) are commonly prescribed DMTs in the United States, but, to our knowledge, there is no randomized clinical trial and limited real-world evidence for head-to-head comparison between these DMT pairs.”

Researchers conducted the current comparative effectiveness study to compare relapse outcomes between dimethyl fumarate vs. fingolimod and natalizumab vs. rituximab. They integrated data from a clinic-based MS research registry and its linked EHRs system between Jan. 1, 2006, and Dec. 31, 2016. Further, they created treatment groups for each pairwise DMT comparison based on both registry records and electronic prescriptions. The 1-year and 2-year relapse rates, as well as the time to relapse, served as the main outcomes. Hou and colleagues adjusted for covariates from two sources and corrected for confounding biases among the covariates by the doubly robust estimation to compare relapse outcomes.

Treatment group demographics were as follows:

• dimethyl fumarate, n = 260; 76.2% women; 87.3% non-Hispanic white individuals; mean age at diagnosis, 41.7 years;

• fingolimod, n = 267; 71.2% women; 83.1% non-Hispanic white individuals; mean age at diagnosis, 37.9 years;

• natalizumab, n = 204; 78.4% women; 84.3% non-Hispanic white individuals; mean age at diagnosis, 37.2 years; and

• rituximab, n = 115; 72.2% women; 99 non-Hispanic white individuals; mean age at diagnosis, 44.1 years.

Hou and colleagues reported no significant differences in the relapse outcomes between dimethyl fumarate and fingolimod after they corrected for confounding biases and multiple testing ([difference in 1-year relapse rate = 0.028; 95% CI, –0.031 to 0.084]; [difference in 2-year relapse rate = 0.071; 95% CI, 0.008-0.128]; [relative risk of 2-year non-relapse = 0.957; 95% CI, 0.884-1.035] with dimethyl fumarate as reference). They noted an association between natalizumab and higher relapse rate for all three outcomes after bias correction and multiple testing upon comparing it with rituximab ([difference in 1-year relapse rate = 0.080; 95% CI, 0.013-0.137; difference in 2-year relapse rate = 0.132; 95% CI, 0.043-0.189; relative risk of 2-year non-relapse = 0.903; 95% CI, 0.822-0.944]). Further, they identified confounders from EHR data not recorded in the registry data via data-driven feature selection.

“These findings based on high-dimensional modeling that incorporates EHR data address knowledge gaps in MS treatment guidance where randomized clinical trials are unavailable and likely infeasible,” Hou and colleagues wrote. “Future studies examining outcomes of long-term disability and ‘no evidence of disease activity’ are warranted. Our approach is potentially applicable to the broader treatment comparison field based on real-world evidence, particularly when research registry data are lacking while EHR data are readily available.”