Obesity Stymies RA Treatment. But Why?

Being overweight or obese not only increases the risk of rheumatoid arthritis developing in the first place; it also makes RA worse and decreases chances for remission, recent studies suggest.

The increased risk for developing RA has been documented by a huge prospective study, including two separate cohorts: the 220,000 women taking part in two successive rounds of the US-based Nurses’ Health Study (NHS and NHSII).¹

Rheumatoid arthritis patients in NHSII (the later cohort) were younger (median age 34 vs 43) and more likely to be obese (11.8% vs 8.3%) and also tended to be diagnosed sooner, on average at an earlier age, by about 10 years. The data allow the researchers to propose that obesity has a dose-response effect on the risk for RA: Every 10 cumulative years of obesity confers a 37% increase in risk.

Now a study of 343 men and women in the UK with established RA has found that a decade of obesity also reduces by more than half the likelihood of sustained remission.²

The researchers studied RA patients (two thirds of them women, with an average age of 61) who had been taking conventional disease modifying antirheumatic drugs (DMARDs) for RA that had been diagnosed on average a decade earlier. Those whose body mass index (BMI) was 30 or above were only about substantially less likely to have achieved remission after one year (3%) or to have sustained remission up to three years (8%) than the normal-weight patients (13% and 17%, respectively).

Those reaching remission, defined as a disease activity score in 28 joints (DAS28) below 2.6, tended to be younger (in their late 50s), female, and to test negative for rheumatoid factor (RF).²

These findings come on the heels of a Swedish study published last May that found being overweight or obese (a BMI of 25 or above) at the time of an RA diagnosis decreases the odds of good disease control as well as pain control.³

In the Epidemiological Investigation of risk factors for Rheumatoid Arthritis (EIRA) study cohort, results were similar to those in the UK study. Overweight or obese patients had a only about half a normal-weight patient's chance of achieving lower disease activity (DAS28 under 3.2) within six months.³

Having a higher BMI also decreased by 48% the odds of reaching remission (DAS28 of 2.6 or below), and reduced by 43% the chance of pain remission during the early stage of the disease, as judged by a visual-analogue scale (VAS-pain).³

How Does Weight Affect RA?

Most of the Swedish patients received methotrexate at the time of diagnosis, and the researchers speculate that overweight may increase intolerance or somehow decrease the effectiveness of the drug in early RA.

The authors of the UK study speculate that obesity may lessen the odds of achieving a good treatment response partly by increasing levels of C-reactive protein (CRP) and inflammatory cytokines. But reviewers from Israel and France, who have assessed the link between obesity or overweight in RA and six other autoimmune diseases, offer an even more specific explanation. ⁴

Inflammatory cytokines secreted by fatty tissue may increase comorbidities in RA, worsen the course of the disease, and lessen treatment efficacy, they agree.

Based on extensive clinical data and experimental models, they also propose that adipokines such as leptin, adiponectin, and resistin promote autoimmune disease by up-regulating immune responses, T-cells, and autoantibodies, and by increasing systemic inflammation.

Their systematic literature review of obesity in RA and other autoimmune disorders finds that obese people may have more than three times greater odds of developing RA and as much as a six times greater risk for PsA.

References:

 1.  Lu B, Hiraki L, Sparks JA, et al., Being overweight or obese and risk of developing rheumatoid arthritis among women: a prospective cohort study. Ann Rheum Dis (2014) Online first Jul 23, 2014. doi:10.1136/annrheumdis-2014-205459.

2.  Ellerby N, Mattey DL, Packham J, et al. Obesity and comorbidity are independently associated with a failure to achieve remission in patients with established rheumatoid arthritis.Ann Rheum Dis (2014) Online first Aug 8, 2014 doi:10.1136/annrheumdis-2014-206254.

3.  Sandberg MEC, Bengtsson C, Källberg H et al., Overweight decreases the chance of achieving good response and low disease activity in early rheumatoid arthritis.Ann Rheum Dis (2014) Online first May 12, 2014. doi:10.1136/annrheumdis-2013-205094.

4.   Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: Not a passive bystander.Autoimmun Rev (2014) Aug 1 doi: 10.1016/j.autrev.2014.07.001. [Epub ahead of print].