NORD-STAR trial reveals obesity linked to reduced treatment efficacy in early rheumatoid arthritis patients

A recent Nordic Rheumatic Diseases Strategy (NORD-STAR) Trials and Registries trial, published in the journal Rheumatic & Musculoskeletal Diseases Open, sheds light on the impact of obesity on treatment outcomes among individuals with untreated early rheumatoid arthritis (RA). The study, which followed participants for up to 48 weeks, revealed that regardless of the type of randomized treatment administered, obesity was consistently linked to a decreased likelihood of achieving a positive treatment response. 

The study involved 793 participants randomly assigned to one of four treatment groups namely active conventional treatment, certolizumab-pegol, abatacept, and tocilizumab. During the follow-up period, participants with obesity at the beginning of the study had higher disease activity compared to those with lower BMI, despite having similar disease activity at the beginning of the study. In survival analyses, obesity was found to be associated with a lower likelihood of achieving response to treatment during follow-up for up to 48 weeks. Specifically, the chances of achieving CDAI remission, SDAI, and DAS28-CRP <2.6 were lower for obese participants (CDAI remission, HR 0.84, 95% CI 0.67 to 1.05; SDAI, HR 0.77, 95% CI 0.62 to 0.97; DAS28-CRP <2.6, HR 0.78, 95% CI 0.64 to 0.95). The study found no evidence to suggest that the effect of obesity on response to treatment varied across the different treatment groups. 

Obesity has been identified as a risk factor for RA, and studies indicate that it is not a reliable indicator of remission in patients treated with biologics. This is attributed to the pro-inflammatory cytokines like TNF-α and IL-6 produced by adipose tissue in the body. Higher fat mass leads to increased cytokine production, potentially impacting treatment effectiveness. 

The findings from this study emphasize the significant influence of obesity on treatment response in individuals with untreated early RA, regardless of the specific treatment received. Given the heightened disease burden associated with both obesity and RA, it is crucial to prioritize close monitoring and potentially optimize antirheumatic therapies for individuals dealing with both conditions. This proactive approach may mitigate the risk of treatment failure and ultimately improve the overall management of early rheumatoid arthritis in patients affected by obesity. 

 Reference 

  1. Dubovyk V, Vasileiadis GK, Fatima T, Zhang Y, Kapetanovic MC, Kastbom A, et al. Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study. RMD Open. 2024 Apr 4;10(2):e004227. 
  1. Francisco V, Pino J, Gonzalez-Gay MA, Mera A, Lago F, Gómez R, et al. Adipokines and inflammation: is it a question of weight? Br J Pharmacol. 2018 May;175(10):1569–79.