Examining Heterogeneity in Response to Disease-Modifying Therapy in Multiple Sclerosis

The results from clinical trials typically provide an average treatment effect which is then used in clinical decision making for an individual patient. Multiple sclerosis (MS) is a chronic neurological disease with considerable heterogeneity, or differences, in outcomes. These differences may also extend to how a person responds to an MS drug – this is called “heterogeneity of treatment effect” (HTE). For example, the effect of an MS drug might be larger for younger individuals with relapsing remitting MS (RRMS, a type of MS that's characterized by periods of symptom flare-ups, or relapses, followed by periods of recovery, or remissions) who have multiple gadolinium-enhancing lesions (areas of damage that show up more clearly when the chemical gadolinium is injected into the patient before a magnetic resonance imaging (MRI) scan) than for older individuals with secondary progressive MS (SPMS, where disability steadily worsens) without gadolinium-enhancing lesions.

The traditional way of looking at HTE have serious limitations and most findings have not been replicated in many non-MS studies. New approaches to looking at HTE aim to provide prediction of someone’s treatment benefit using multiple patient factors at the same time and are important for personalizing care.

A few prior studies suggested that HTE may be present in clinical trials and affect outcomes in MS. For example, two proof-of-concept studies exploring HTE for relapses identified responders using a patient-specific score based on age, sex, the number of relapses prior to start the trial. However, these studies used an approach that is not the recommended approach to study this question.

We plan to use rigorous, recommended approaches to understand if there are differences in outcomes based on a set of multiple characteristics to improve identification of the optimal treatment for an individual patient.

Our study will use existing data collected from multiple clinical trials designed to test how well MS drugs work in MS. In clinical trials, data are collected carefully, at regular intervals, and in large numbers of people. We will use these data and the recommended approaches to find characteristics, including comorbidities (other illness occurring at the same time) that may be associated with MS outcomes. We will also use these data to find out if HTE are present in MS clinical trials and what characteristics are associated with how well a MS drug works. We hope that this information will help people with MS and their clinicians make more informed and personalized decisions about treatment.

In the future, we expect the results of this study to encourage future trials to report HTE and allow for more personalized treatment decisions as new MS drugs become available and influence design of clinical trials of future MS drugs in MS.