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Explore This IssueAugust 2022
1) Obesity & Treatment Response in RA
Obesity & response to advanced therapies in rheumatoid arthritis
Why was this study done? There have been questions regarding whether certain therapies for rheumatoid arthritis (RA) are less effective in patients with obesity, particularly for tumor necrosis factor (TNF) inhibitors, because adipose tissue is known to generate TNF, among other inflammatory mediators.
What were the study methods? We studied 5,901 patients enrolled in the CorEvitas registry who were initiating a TNF inhibitor or a non-TNF inhibitor biologic. We used linear and logistic regression to look at response to therapy across a range of body mass indexes (BMI). We first looked at response to any therapy, then tested to see whether any observed effect of obesity on response differed between those initiating a TNF inhibitor and those initiating a non-TNF biologic. We adjusted analyses for potential confounding factors, such as age, disease activity and comorbidities.
What were the key findings? There were three main observations. First, obesity was associated with a reduced response to therapy, although the effect was modest after adjustment. Specifically, patients with obesity had modestly lower odds of achieving low disease activity six months after starting a biologic therapy (odds ratio [OR]=0.88).
Second, there was no difference in this effect whether the person received a TNF inhibitor therapy or a non-TNF inhibitor therapy, suggesting the lack of response in this group was not treatment specific.
Third, underweight patients were much less likely to respond to both types of therapies (OR=0.32) even after adjustment. With regard to these observations, it didn’t seem to matter whether the medication used weight-based dosing.
What were the main conclusions? Although obese and underweight patients may indeed show lower responses to therapy, this is not therapy specific.
What are the implications for patients? When starting therapy, underweight and obese patients should recognize the treatment may not be as effective for them as for others—although it’s not clear the treatment strategy should be different.
What are the implications for clinicians? The impact of obesity on health is broad, which may explain why lower clinical responses are observed for multiple types of therapies with different mechanisms of action. Obesity may cause persistent symptoms of obesity-related conditions (e.g., osteoarthritis, fibromyalgia) and promote systemic inflammation through release of cytokines and adipocytokines. Underweight patients may have experienced cachexia due to a high burden of systemic inflammation; this may explain the lower responses observed in this group.