Heterogeneity of Treatment Effect in MS Trials Should Include Multiple Factors

The much recognized diversity in outcomes among patients with multiple sclerosis (MS), accounted for by genes, age, and other key patient factors, may extend to therapeutic responses to treatment. Consequently, evaluating possible heterogeneity of treatment effect (HTE) in MS clinical trials has garnered increased interest, explains a review article published in the journal Multiple Sclerosis.

The article was published by, and on behalf of, participants of a December 2022 workshop sponsored by the European Committee on Treatment and Research in MS and the US National MS Society. During the conference, members of the International Advisory Committee on Clinical Trials, biostatistics experts, and other relevant professionals discussed HTE assessment methods in MS clinical trials.

“HTE refers to non-random variation in the magnitude or direction of the effect of treatment on a clinical outcome of interest in different patient subgroups defined by one or more covariates,” the authors wrote. “For example, the effect of a disease-modifying therapy might be larger for younger individuals with relapsing-remitting MS who have multiple gadolinium-enhancing lesions than for older individuals with secondary progressive MS who do not have gadolinium-enhancing lesions.”

HTE can be assessed using multiple statistical techniques, including the most simple, widely used, and biased method: the one-variable-at-a-time subgroup analysis. Nevertheless, multivariable predictive approaches have been put forth that account for multiple relevant patient characteristics simultaneously. These approaches, explained in the review article, are foundational to personalized, evidence-based medicine and important for use in MS clinical trials, according to the piece.

“The need to identify ‘responders’ to therapies is urgent in MS, since many treatments are available, and the response to each drug is highly heterogeneous,” the authors wrote. “To personalize the use of disease-modifying therapy, we must ensure that we capture and share standardized demographic, clinical, and biomarker-based characteristics that may influence outcomes, including comorbidities and social determinants of health.”

Reference

Sormani MP, Chataway J, Kent DM, Marrie RA. Assessing heterogeneity of treatment effect in multiple sclerosis trials. Mult Scler. 2023;29(9):1158-1161. doi:10.1177/13524585231189673