Obesity at Baseline is a Risk Factor for Poor Treatment Response in RA

Violetta Dubovyk

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Among patients with untreated early rheumatoid arthritis (RA) for up to 48 weeks, obesity was linked to a lower likelihood of good treatment response, regardless of the type of treatment received, according to a study published in Rheumatic & Musculoskeletal Diseases.¹

Although several treatment options are currently available for this patient population, there are no methods to precisely predict if a patient will respond well to a certain treatment and current approaches have demonstrated insufficiencies regarding the choice of disease-modifying antirheumatic drugs (DMARDs). This is important as treatment failure is associated with increased complications and reduced quality of life among these patients.²

“Obesity is an established risk factor for developing RA,” wrote a team of investigators led by Violetta Dubovyk, a research assistant at the Department of Rheumatology and Inflammation Research, University of Gothenburg, Sweden. “Moreover, people with RA that have overweight or obesity more often need combination therapy and may have lower chance to achieve low disease activity or remission compared with normal-weight people, although this is debated especially for those treated with bDMARDs. Whether obesity affects the response to antirheumatic treatment in early RA is less clear as both similar and lower chances to achieve remission have been reported for people with obesity compared with those with lower body mass index (BMI).”

To determine if obesity is associated with treatment response to conventional and biological DMARDs (cs/bDMARDs) in adult patients with newly diagnosed RA, investigators used data from the randomized, longitudinal Nordic Rheumatic Diseases Strategy Trials and Registries (NORD-STAR) trial. The BMI of eligible patients was assessed at baseline and obesity was defined as BMI ≥ 30 kg/m².

Inclusion criteria included a symptom duration of < 24 months, patients had ≥ 2 swollen joints and ≥ 2 tender joints, had a Disease Activity Score with 28 joints using C-reactive protein (DAS28-CRP) score of > 3.2, and exhibited either rheumatoid factor (RF) positivity, CRP ≥ 10 mg/L, or anti-citrullinated protein antibody (ACPA) positivity.

Patients were randomized into 4 treatment arms: conventional treatment, abatacept, tocilizumab, and certolizumab-pegol. The primary endpoint was the response to treatment using Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) remission, and the DAS28-CRP < 2.6 stratified by BMI. Measurements were collected at baseline, and weeks 8, 12, 24, and 48.

Of the 793 patients included in the analysis, 20% (n = 161) had obesity at baseline. During the follow-up period, data show patients with baseline obesity had higher disease activity than those with a lower baseline BMI, despite similar disease activity at baseline.

According to survival analyses, obesity was linked to a lower likelihood of obtaining response to treatment during the follow-up period (CDAI remission, hazard ratio [HR] .84, 95% confidence interval [CI] .67 to 1.05; SDAI, HR .77, 95% CI .62 to .97; DAS28-CRP <2.6, HR .78, 95% CI .64 to .95).

Obesity’s effect on treatment response was not influenced by the mode of treatment.

Investigators noted determining obesity using BMI as a limitation of the study because it is not a marker of adipose distribution and the difference in the ratio between adipose tissue and muscle may account for the adverse effects seen in treatment response.

“Owing to the disease burden associated with these conditions, people with early RA having obesity need a careful follow-up and possibly optimization of antirheumatic treatments in order to avoid treatment failure,” investigators concluded.

References

1. ^{Dubovyk V, Vasileiadis GK, Fatima T, et al. Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study. RMD Open. 2024;10(2):e004227. Published 2024 Apr 4. doi:10.1136/rmdopen-2024-004227}
2. ^{Wijbrandts CA, Tak PP. Prediction of response to targeted treatment in rheumatoid arthritis. Mayo Clin Proc 2017;92:1129–43. doi:10.1016/j.mayocp.2017.05.009}