One common MS treatment, Ocrevus (ocrelizumab), has had low numbers of minority participants in its clinical trials so far. In studies that compared Ocrevus with another treatment, Rebif (interferon beta-1a), 91 percent of participants were white, 4 percent were Black or African American, and 5 percent belonged to other racial or ethnic groups. And in a study that compared Ocrevus with a placebo (inactive treatment), 94 percent of participants were white, 2 percent were Black or African American, and 4 percent belonged to other groups. In each of these studies, minority enrollment was so low that the researchers couldn’t determine any significant differences or similarities between racial or ethnic groups. In fact, the published studies didn’t even show results by race or ethnicity, as noted in an editorial published in January 2019 in the journal CNS Spectrums.
Why Is Minority Participation So Low in MS Drug Trials?
The lack of minority participation in MS clinical trials can probably be blamed on a variety of factors. “When trials are created, sometimes there are very strict criteria around, for instance, control of diabetes or hypertension,” explains Mitzi Joi Williams, MD, a neurologist and MS specialist with Joi Life Wellness Group, a private practice in Atlanta. “And that may automatically exclude populations that have higher rates of these other medical problems.” Other potential barriers to minority enrollment, Dr. Williams says, include the limited number of MS centers that recruit for clinical trials, and reluctance on the part of some groups to participate in trials. In particular, low enrollment of Black Americans in clinical trials is unfortunate because, by some estimates, this group has the highest risk of MS among racial and ethnic groups in the United States. According to research, including a study published in November 2016 in Multiple Sclerosis Journal, Black and Hispanic Americans with MS tend to experience greater disability than their white counterparts at the same point in the course of their disease. So it’s no small thing that a new clinical trial of Ocrevus, called CHIMES (Characterization of Ocrelizumab in Minorities With Multiple Sclerosis), is the first to focus on how an MS treatment affects minority groups — in this case, “self-identified African American and Hispanic or Latin American participants with a diagnosis of relapsing multiple sclerosis,” according to the study description posted on ClinicalTrials.gov. Here’s what you should know about what researchers aim to learn from this study, and how these findings could change how MS is studied and treated.
Researchers Seek Clues About Racial Disparities in MS
Williams, a lead investigator of CHIMES, says that the study grew out of conversations she and others had as part of a committee on advancing inclusive research at Roche and Genentech, the parent pharmaceutical company and subsidiary, respectively, behind Ocrevus. “Particularly in the Black community, people have to use walking assistance, like canes and walkers, up to six years earlier than their white counterparts,” Williams notes. “Because we have very low enrollment of minority patients in our clinical trials, we don’t have a good understanding of why we’re seeing these outcomes.” One possibility, Williams says, is that MS affects Black and Hispanic people differently because of biological differences, which may be revealed by looking at a variety of genetic markers. But it’s also possible that some, or even all, of the differences in outcomes are due to disparities in social determinants of health — factors like economic status, access to healthcare, or stress caused by racial discrimination. Ocrevus was the logical choice for a study like CHIMES, Williams says, both because of the discussions in progress at Roche and Genentech and because “there is some evidence to suggest that the pathway that Ocrevus uses” — known as the B-cell pathway — “may be a pathway that has more activation in Black patients.” But CHIMES may not be the only study of its kind in the next few years. “Since this trial has kicked off, I can say there are other groups that have been interested in conducting similar trials with their products,” says Williams. RELATED: MS in Black Americans: Research Challenges Old Beliefs
Study to Examine MS Outcomes and Genetic Markers
The CHIMES study has been shaped by discussions involving many different parties, says Williams. “We had researchers, subject experts in the field. We had geneticists involved, and we had patients involved.” In many ways, CHIMES will follow the design of a previous clinical trial, known as OBOE (Ocrevus Biomarker Outcome Evaluation), that looked at how treatment with Ocrevus corresponded to certain biomarkers in blood and cerebrospinal fluid. Because of its similarity in design to previous studies, CHIMES won’t include a control group — instead, all participants will receive Ocrevus. CHIMES will look not only at genetic markers associated with MS, but also at outcomes that are more typical for studies of MS treatments, including disease relapses, measures of disability, and MRI results. Only a small subset of participants will undergo lumbar puncture and have their cerebrospinal fluid analyzed for markers of MS disease activity. The overall goal, says Williams, is to understand how Black and Latino Americans with MS respond to treatment when certain aspects of their care are the same as for white Americans. “One reason clinical trials are important is that it’s a controlled setting,” Williams explains. “Everybody has the same access to care, to MRIs, to medications. And there are certain ways we measure if someone has a relapse. Things are standardized.” If, at the end of the study, there don’t seem to be any major differences in the biology of MS between Black and Hispanic participants and previous white participants, it will be a clue that differences in how these minority groups experience disease progression are mostly due to social determinants of health, says Williams. But if there are significant biological differences that seem to explain the faster disease progression seen in Black and Hispanic Americans, it will be even more important to continue to explore how various MS treatments may benefit different groups of people. “One of the goals of medicine now is personalized medicine, to be able to look at a certain person’s markers and determine what would be the best treatment for that person,” says Williams. In the future, that may mean looking at the results of several blood tests to determine which MS treatment is most likely to be beneficial. RELATED: How the High Price of MS Drugs Affects People’s Lives
CHIMES Trial Now Recruiting, Slightly Differently
The CHIMES trial began recruiting participants in July 2020, with the goal of mostly completing this process within 12 to 18 months. The study will have 150 to 200 participants, depending on how many people decide to enroll in the substudy involving lumbar puncture. Half of the participants will be Black Americans, and half will be Hispanic. Williams notes that the design of CHIMES has been modified in a few ways to address barriers to minority recruitment that are commonly seen in clinical trials. One of these changes has been slightly altering inclusion and exclusion criteria — such as age and health issues like kidney function. “We’ve relaxed some of these criteria to a degree, where it wouldn’t interfere with the study, to allow more inclusivity,” Williams explains. Another change has been to involve MS centers that serve large minority populations, even if they’re not necessarily the most common sites of clinical trials. A total of 30 sites for the study have been selected, spanning different regions of the United States. So far, 10 sites are actively recruiting, with six people fully enrolled in the study and many others in the screening process. Williams hopes that CHIMES marks the beginning of a renewed focus on diversity in clinical trial participants — concerning not just race and ethnicity, but also traits like age, since many MS studies exclude people over age 55. “If you don’t have diverse participants in studies, it’s going to be very hard to generalize the results,” Williams emphasizes. “There are sometimes subtle differences in groups that may inform our treatment decisions.” Going forward, Williams would like to see a wider range of participants in the initial clinical trials for MS treatments, so that studies like CHIMES are less essential. “When we have more diversity, it increases the richness of our data,” she notes. “And for patients, it’s about having their voices counted. We want everybody to be a part of the conversation.” If you or someone you know may be a candidate for CHIMES, you can find more information about enrollment on its official page at ClinicalTrials.gov.
