The discussion of RA pathogenesis is just the first part. Outcomes are also an important piece of the RA/obesity/inflammation puzzle.
Impact on RA Outcomes
“Investigating the effect of obesity on RA outcomes may not be as clean as preclinical pathogenesis because there are more confounding factors, such as medications, diet changes and changes in physical activity,” says Dr. Sparks. “But overall, most of the findings indicate that obesity is also important in patients with established RA.”
One of the more compelling indicators of the possible link between outcomes in RA and BMI is Dr. Sparks’ recent research into what happens to RA following extensive weight loss from bariatric surgery. They hypothesized that adiposity was driving RA activity and that it would improve following recovery.15
They found major positive outcomes among patients. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) markers for inflammation were dramatically reduced from baseline (28.1 to 4.1 mg/L and 45.7 to 18.0 mm/hr, respectively) at the most recent follow-up. Following bariatric surgery, patients had significant improvements in RA disease activity and reductions in use of RA-related medications.
“What really hit home clinically from my perspective was the sheer number of RA patients in remission,” says Dr. Sparks. “Almost one in every four patients had no symptoms and were off all RA-related medications one year after bariatric surgery. That is almost unheard of among RA patients in any other setting.”
Another large study out of Sweden used the Disease Activity Scale 28 (DAS28) responses at two different time points. Increased BMI was associated with an increase in DAS28. In addition, obesity decreased the odds of being in remission. These were seen after adjusting for confounders such as steroid use, age, and gender.16
Dr. Sparks’ group performed a cross-sectional study of another cohort of RA patients using the Clinical Disease Activity Index (CDAI). Among those with normal BMI, only 30% were classified as having moderate or high disease activity. That flipped among obese patients with nearly 75% deemed to fit those two categories.17
However, increased BMI might paradoxically be protective for some long-term outcomes, particularly in joint damage and erosions in several studies according to Dr. Sparks. Even when stratified by ACPA status, the protective effect of obesity on radiographic damage remains.
“Currently, there are a lot of indicators both on the mechanistic and epidemiological side that give credence to the thought that obesity may have an impact on RA,” said Sparks. “However, at this time the best we can say is that it is an interesting, but fairly well supported, hypothesis. Further studies are needed to investigate the interesting and important interaction between obesity and RA.”
