Lower body mass and lower adiposity are associated with differential responses to two treatment strategies for rheumatoid arthritis

Abstract

PurposeTo determine if body mass index (BMI) and adipokine levels identify rheumatoid arthritis (RA) patients most likely to benefit from initiation of tumour necrosis factor inhibitors (TNFi) after methotrexate inadequate response.MethodsThis is a secondary analysis of the Rheumatoid Arthritis Comparison of Active Treatments (RACAT) trial and the (TEAR) trial. Both studies compared treatment strategies starting with conventional disease-modifying anti-rheumatic drugs (DMARDs) (triple therapy) versus etanercept plus methotrexate. We compared response rates between TNFi and triple therapy among patients with different BMI. Adipokines were measured at enrolment and associations with treatment response were examined using regression, adjusting for age, sex, BMI and baseline disease activity.ResultsIn RACAT (n=306), participants who were normal/underweight were more likely to benefit from TNFi versus triple therapy, with greater change in Disease Activity Score in 28 and greater ACR20 response (ACR 20: 64% vs 23%, p=0.001). In contrast, overweight/obese participants had similar response to TNFi versus triple therapy (p-for-interaction=0.001). Similarly, but modest patterns were observed in TEAR (n=601; ACR20: 67% vs 52%, p=0.05). In RACAT, adipokine scores consistent with lower adiposity also predicted greater response to TNFi (ACR20: 58% vs 37%, p=0.01) with better model fit compared with BMI alone.ConclusionsLower BMI and evidence of lower adiposity based on adipokine profiles were associated with a superior response to TNFi compared with triple therapy. There was no difference between treatments among overweight/obese participants. The results support TNFi being a particularly important therapeutic among normal/underweight patients, with implications for clinical decisions and trial design.

Novel insights into the management of rheumatoid arthritis: one year in review 2024

“…In contrast, no significant difference was observed among obese or overweight patients and those with higher adiposity findings. These findings suggest an increased probability of achieving therapeutic goals through the early initiation of TNF inhibitors in patients with lower BMI (35).…”

Sleep duration and the risk of new-onset arthritis in middle-aged and older adult population: results from prospective cohort study in China

“…This also elucidates why our study findings indicate that BMI acts as a pivotal moderating factor for both reduced sleep duration and increased new-onset risk of arthritis, corroborated by stratified analysis and mediation analysis. And stratified analysis also showed that being underweight (BMI < 18.5) may have the strongest regulatory effect, which indirectly explains why arthritis patients with lower body weight tend to respond better to specific treatments ( 51 ). In addition, reduced sleep duration also stimulates an increase in the secretion of various thyroid hormones ( 47 ).…”