Leflunomide and Weight Loss in Rheumatoid Arthritis Save

Weight change can have substantial effects on the outcomes of patients with arthritis. It has long been known that weight loss and low body mass index (BMI) are associated with poorer arthritis outcomes.  Moreover, obesity has been shown to impair drug responses to both DMARDs and biologics. While the new agent apremilast is known to induce weight loss in a minority of patients, it is unclear if other DMARDs are capable of the same. This is especially an issue for leflunomide, wherein weight loss has been noted in some patients.  

In the current issue of Arthritis & Rheumatology, Baker and colleagues studied if the DMARD therapies used in rheumatoid arthritis (RA) may influence changes in BMI.  

Using administrative data from the US Veterans Administration pharmacy database, they assessed the effects of therapy on C-reactive protein (CRP) and BMI (within 30 days of drug start) for the following therapies: methotrexate, prednisone, leflunomide and tumor necrosis factor inhibitors (TNFi).  Weight loss was defined as a decrease in BMI of >1 kg/m².

They analyzed 52,662 treatment courses in 32,859 patients.  Weight loss was associated with older age, greater baseline CRP, greater baseline BMI, CCP seropositivity, disease duration >5 years, history of malignancy or lung disease.  

Weight gain was seen at 6 months among users of methotrexate, prednisone, and TNFi, with prednisone-treated patients having significantly more weight gain.

Weight loss was observed in those receiving leflunomide. In multivariate analyses, more weight loss was seen among leflunomide users (compared to MTX) and an overall greater risk of weight loss (OR 1.73).  Leflunomide is associated with significant but modest weight loss compared to other RA therapies, while prednisone is associated with greater weight gain.  Sensitivity analyses with or without those who discontinued the drug early show the same results, suggesting that weight loss with leflunomide is not simply due to poor response and resulting treatment failure.