TOPLINE

Adults with rheumatoid arthritis (RA) who had a higher BMI had poorer clinical responses to JAK inhibitors than those with healthy weight.

METHODOLOGY

• Researchers conducted an individual patient data meta-analysis of 16 phase 3 randomized controlled trials to assess whether BMI modified response to JAK inhibitors in 11,883 patients with RA (mean age, 52.9 years; 80.7% women).
• Patients were randomly assigned to receive JAK inhibitors (tofacitinib, baricitinib, or upadacitinib), placebo, methotrexate, or biologic comparators.
• Baseline BMI was categorized as underweight (< 18.5), healthy weight (18.5 to < 25), overweight (25 to < 30), obesity class 1 (30 to < 35), obesity class 2 (35 to < 40), and obesity class 3 (≥ 40). Patients had a median BMI of 26.8.
• The primary outcomes were 20% improvement based on the American College of Rheumatology core set variables (ACR20) and Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) at the trial-defined primary efficacy timepoint, typically 12 weeks.
• Researchers assessed the risk for bias and quality of studies.

TAKEAWAY

• Compared with patients having a healthy weight, the adjusted relative risk (RR) for ACR20 response in the JAK inhibitor group was 0.94 in those with overweight, 0.92 in those with obesity class 1, 0.88 in those with obesity class 2, and 0.78 in those with obesity class 3 (P < .01 for all). No corresponding BMI trend was noted in patients who received placebo.
• Each 1-unit increase in BMI was associated with a 0.02-unit increase in DAS28-CRP (P < .0001). Patients with overweight or obesity classes 1-3 had higher adjusted mean DAS28-CRP than those with a healthy weight (P < .0001 for all).
• For ACR20, interaction analyses showed the JAK inhibitor benefit over placebo was significantly attenuated in overweight and obesity class 2, borderline in obesity class 3, and not significant in obesity class 1.
• The risk for bias across studies and between-study heterogeneity were both low to moderate.

IN PRACTICE

"[The] findings underscore obesity as an important modifier of treatment outcomes and highlight the need for future trials to adequately represent the full spectrum of BMI seen in clinical practice to ensure generalizability of treatment effects," the authors of the study wrote.

"By moving beyond simple association to formal interaction testing, the study offers a more precise framework for interpreting nonresponse in patients with excess weight and for embedding BMI into therapeutic decision-making," Chary Lopez Pedrera and Carlos Perez Sanchez wrote in a related comment.

SOURCE

The study was led by Katie Bechman, PhD, King's College London, England. It was published online on August 3 in The Lancet Rheumatology.

LIMITATIONS

Limiting the analysis to phase 3 trials might have limited the generalizability of the findings. Data for filgotinib were unavailable. BMI was measured only at baseline, preventing the assessment of weight change during follow-up.

DISCLOSURES

The study did not receive any funding. Several authors disclosed receiving honoraria, consulting fees, or grants from pharmaceutical companies, including Eli Lilly, UCB, and Vifor Pharma. Some authors reported serving on the advisory boards of many of these companies. Detailed author disclosures are reported in the original article.

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