Black People Underrepresented in Pivotal Inflammatory Arthritis Clinical Trials

Despite strides to diversify research, people of color, especially Black people, are still widely underrepresented in inflammatory arthritis clinical trials, according to a new study.¹

“Racial/ethnic disparities in clinical trials have long been a challenge in all therapeutic areas such as cancer, eye disease, and cardiovascular disease,” wrote the investigators.

Racial or ethnic minority groups face higher disease burdens, such as higher disease activities, worse global health scores, and greater pain, and yet they often get overlooked in research.^2-5 To ensure diversity, there are academic and regulatory authorities’ guidelines.

The U.S. National Institutes of Health (NIH) published policy and guidelines stating NIH-funded clinical research must include people of minority groups. Moreover, in 2017, the NIH published an amendment in 2017 requiring phase III clinical trials to address race/ethnicity differences. Not only that, but the FDA also created plans to improve data analyses by addressing demographic subgroups in medical review and labeling.¹

In the new study led by Yan Xie, of the department of rheumatology and immunology at Sichuan University in Chengdu, China, the investigators systematically reviewed new inflammatory arthritis drugs approved by the FDA from July 2012 – June 2022.

From there the team examined the clinical trials that tested these drugs. The investigators identified 34 new drug approvals, and the number of approvals for each drug subtype was: 11 for psoriatic arthritis, 6 for rheumatoid arthritis, 10 for spondyloarthritis, and 7 for juvenile idiopathic arthritis. The 15 new drugs included 11 biologics and 4 small molecule inhibitors. Drug approvals were based on 59 clinical trials, distributed in North America, South America, Europe, and Asia.

“Different countries have unique population demographics and varying policies for trial enrollment, potentially hindering the generalizability of global clinical trials,” the team wrote.

The team grouped the racial and ethnic categories as White, Black, Asian, and Hispanic or Latino, based on the standards issued by the Office of Management and Budget for the Classification of Federal Data on Race and Ethnicity, as well as the way most of the trials categorized racial and ethnic groups. In these trials, Black people were consistently underrepresented while White people were overrepresented, in comparison to 2020 census data.

The pivotal trials showed relative heterogeneities in enrollments for Asian and Hispanic participants. Over time, White people were observed to have increased involvements for rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis trials. The investigators observed increased involvement of Black participants and decreased enrollment of Asian and Hispanic participants in rheumatoid arthritis.

For rheumatoid arthritis, the 6 new drug approvals were based on 17 clinical trials. The trials included 13,159 participants with 80% White, 4.2% Black, 12.5% Asian, and 30% Hispanic. Relative to the 2020 US census data, White, Asian, and Hispanic participants were overrepresented, but Black participants were underrepresented.

White participants were overrepresented in 13 trials and underrepresented in 2. Black participants were underrepresented in 16 trials. Asian participants were overrepresented in 9 trials and underrepresented in 2 trials. Hispanic participants were overrepresented in 6 trials and underrepresented in 1 trial.

For psoriatic arthritis, the 11 drug approvals were based in 21 trials. The trial included 11,372 participants, with 93.9% White, 0.6% Black, 5.4% Asian, 16.6% Hispanic, although the data only came from 5 trials.

The investigators found White participants were overrepresented in all 21 trials, Black participants were underrepresented in 16 trials, Asian participants were overrepresented in 2 trials and underrepresented in 8 trials, and Hispanic participants were underrepresented in 1 trial.

As for spondyloarthritis, 13 trials were conducted, containing 3897 participants with 80.8% White, 1% Black, 15.2% Asian, and 8.7% Hispanic. In total, White people participated in 13 trials, Black people participated in 7 trials, Asian people participated in 11 trials, and Hispanic people participated 1 trial.

White, Asian, and Hispanic participants were overrepresented while Black participants were underrepresented. Specifically, White people were overrepresented in 11 studies, and Asian participants were overrepresented in 8 studies and underrepresented in 1.

Then, for juvenile idiopathic arthritis, the 7 drug approvals were based in 8 trials, with 83.5% White, 2.9% Black, 33.9% Hispanic. Only 6 trials reported data on race/ethnicity, and 3 of the 6 trials solely provided information on White participants.

While the proportion of white participants for each drug was 70.2% – 97.1%, the proportion of Black participants was 0 – 5.4%. The proportion of Asian participants was 0.2% – 24.9%, and the proportion for Hispanic participants was 5.8% – 50%.

From the first 5 years to the second 5 years of rheumatoid arthritis drug approval clinical trials, the investigators observed an increased involvement of White participants (71.3% vs. 81.4%, P = .000) and Black participants (3.4% vs. 5.1%, P = .000) and decreased involvement of Asian (14.5% vs. 9.7%, P = .000) and Hispanic (36.4% vs. 26.6%, P = .000) participants.

For psoriatic arthritis and spondyloarthritis trials, only white participants had a greater involvement over the years. Whereas data from juvenile idiopathic arthritis trials showed no time trends for race/ethnicity.

“Our results presented an unreasonable distribution of race/ ethnicity in pivotal trials leading to FDA new drug approval during the past 10 years,” the investigators wrote. “It reminds the significance of finding answers to another important problem: if there is a true difference in drug therapeutic responses and adverse reactions among different racial/ ethnic groups.”

References

1. ^{Xie Y, Liu Y, Qin Y, Chen X, Xie Q. Characteristics of race/ethnicity in trials leading to antirheumatic drug approval for inflammatory arthritis by the US Food and Drug Administration. Int J Rheum Dis. 2023;00:1-9. doi:10.1111/1756-185X.14944}
2. ^{Yip K, Navarro-Millán I. Racial, ethnic, and healthcare disparities in rheumatoid arthritis. Curr Opin Rheumatol. 2021;33(2):117-121.}
3. ^{Ogdie A, Matthias W, Thielen RJ, Chin D, Saffore CD. Racial differences in prevalence and treatment for psoriatic arthritis and 1756185x, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/1756-185X.14944 by WOLAHCJ, Wiley Online Library on [21/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License ankylosing spondylitis by insurance coverage in the USA. Rheumatol Ther. 2021;8(4):1725-1739.}
4. ^{Ringold S, Beukelman T, Nigrovic PA, Kimura Y, CARRA RegistrySite Principal Investigators. Race, ethnicity, and disease outcomes in juvenile idiopathic arthritis: a cross-sectional analysis of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. J Rheumatol. 2013;40(6):936-942.}
5. ^{Navarro-Millán I, Rajan M, Lui GE, et al. Racial and ethnic differences in medication use among beneficiaries of social security disability insurance with rheumatoid arthritis. Semin Arthritis Rheum. 2020;50(5):988-995.}