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TOPLINE:

A strong inverse association was found between the socioeconomic status of participating countries and placebo response rates in randomized controlled trials (RCTs) of rheumatoid arthritis (RA). Taking socioeconomic factors into account during trial design and analysis can help account for potential disparities in placebo response rates.

METHODOLOGY:

• Researchers investigated the impact of global recruitment patterns and socioeconomic factors on placebo response rates by analyzing 124 double-blind, multicenter RCTs of targeted therapies (biologic or targeted synthetic disease-modifying antirheumatic drugs) involving 14,272 patients with RA.
• They calculated socioeconomic indicators (gross national income, Human Development Index, and out-of-pocket health expenditures) for every trial based on the number of recruiting centers per country in each study.
• Analysis focused on the proportion of patients in the placebo group who achieved at least 20% improvement according to American College of Rheumatology response criteria at week 12 (± 4 weeks).
• Findings were validated using patient-level data from one global RCT.

TAKEAWAY:

• Between 1994 and 2021, RA trials expanded from being confined to North America and Western Europe to include centers in Eastern Europe, the Asia-Pacific region, and Latin America — especially from 2005 onward; over the same time, the mean normalized gross national income of the conducted studies reduced, and placebo response rates rose by 25%.
• At week 12, a strong and significant negative association was found between placebo response rates and gross national income of participating countries (β, -3.7% placebo response per 10,000 international dollars; P < .001). Similar findings were observed for the Human Development Index and out-of-pocket health expenditures.
• The higher placebo response rates in low-income countries (β, -9.6 ± 3.8%; P = .031) were further confirmed in the analysis of patient-level data from a single global placebo-controlled trial.
• Finally, when comparing this association with response rates in active-treatment arms, active responses remained more stable — implying that trials conducted in low-income countries require larger sample sizes to achieve adequate power.

IN PRACTICE:

“Considering socioeconomic disparities when designing and conducting drug trials in RA appears critical for sponsors, investigators, healthcare providers, and political stakeholders,” the authors of the study wrote.

SOURCE:

This study was led by Andreas Kerschbaumer, MD, PhD, who was an attending physician in rheumatology at the Medical University of Vienna, Vienna, Austria, at the time of the study but is now a postdoctoral scholar in the Division of Immunology and Rheumatology at Stanford University, Stanford, California. It was published online on August 1, 2025, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The study relied on comparing socioeconomic measures at the country level, which may not have captured variability between sites within the same country. Additionally, the analysis was limited to only American College of Rheumatology response rates.

DISCLOSURES:

Some authors reported receiving honoraria, travel support, grants, or consulting fees, participating in speakers bureaus and holding other ties with various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.