GLASGOW, SCOTLAND – Early arthritis patients who are obese are less likely to achieve a good response to disease-modifying antirheumatic drugs in their first year of treatment than their lighter counterparts, judging from the results of a 212-patient study.
The median 28-joint count disease activity score (DAS28) was higher (3.1 vs. 2.6) and fewer patients achieved DAS28 remission (40.3% vs. 52.3%) comparing obese with normal-weight or underweight patients.
A good EULAR response was achieved by 40% of patient who were classified as obese vs. 58.5% of those classified as being of normal weight or underweight.
"There was not much difference in initial treatment across the whole cohort of patients, but at the endpoint of 1 year we found that the obese patients just were not responding as well," said Dr. Stephanie Ling in an interview at the annual meeting of the British Society for Rheumatology.
"This study has highlighted the alarming levels of obesity and poor fitness in a typical well-controlled RA population."
"There are a number of reasons that could be behind this. It could be we are not adjusting the dose to weight, or it could be because of our hypothesis that inflammatory markers are higher in the obese patients anyway."
Dr. Ling of the University of Liverpool (England) and coworkers have previously assessed how obesity affects disease activity in rheumatoid arthritis (RA), finding that the higher the body mass index (BMI), the greater the DAS28 and inflammatory disease activity (Rheumatology News, May 2011, p. 34).
"When we broke down the disease activity score components, there was not much difference between obese and non-obese patients in the tender and swollen joint counts," she said.
"When you got down to the levels of the inflammatory markers in the blood, however, those were statistically significantly raised in the very obese patients." This could be influencing the response to treatment, and possibly explain the impaired response to disease-modifying antirheumatic drugs (DMARDs) that was seen in the present study (Rheumatology 2012;51:iii162–3, abstract P295).
The current investigation assessed the effects of obesity on disease activity in the first year of DMARD therapy in an inception cohort of RA patients who had a symptom duration of less than 1 year.
The mean age of patients was 57.7 years, 60.1% were female, and 71.2% were positive for anticitrullinated protein antibodies (ACPA). The median body mass index (BMI) was 27.5 kg/m2, with a third (34%) of the cohort classified as being obese (BMI greater than 30).
At 1 year, the median DAS28 score for the entire cohort was 2.6, and 51% were in DAS28 remission; 58% had achieved a good EULAR response. When outcomes were split according to BMI, however, the obese patients did significantly worse.
The median DAS28 score in overweight (BMI 25-29.9) patients at 1 year was 2.4; 45% achieved DAS28 remission, and 66.7% achieved a good EULAR response.
A trend for association between obesity and high baseline DAS28 (greater than 5.1) was found (odds ratio, 1.7; 95% confidence interval, 0.9-3.1), which grew stronger when the analysis was limited to patients who were ACPA-positive (OR, 2.0; 95% CI, 1.0-4.0). However, ACPA-positivity by itself was not associated with treatment response at 1 year.
Inverse correlations between baseline obesity and DAS28 remission and EULAR response at 1 year were found to be more prominent in female than male patients.
"I think we definitely need to think about dosing according to weight instead of giving everyone the same dose," Dr. Ling suggested. Dosing by weight is done in pediatric but not adult practice.
Losing weight may also be of benefit but requires further investigation to see if this in itself could help improve the response to therapy. Anecdotally, Dr. Ling noted the case of a woman who had been on high-dose treatment and lost more than 238 pounds and subsequently went into remission, without further need for drug therapy.
Other work presented by Dr. Corrinne Ellis showed that obesity is linked to greater functional disability (Rheumatology 2012;51:iii163, abstract P296). Analysis of data on 803 patients (21% obese) with inflammatory polyarthritis in the Norfolk Arthritis Register (NOAR) revealed that baseline obesity was associated with higher disability, as determined by the Health Assessment Questionnaire (HAQ) at 1 year.
Perhaps the reason HAQ scores are higher in obese patients is because they are just too unfit or obese to exercise. Indeed, other research presented at this meeting showed that cardiorespiratory fitness assessed using a simple step test was low in patients with RA (Rheumatology 2012;51:iii162–3, abstract P80).
Cardiorespiratory fitness is an independent risk factor for heart disease and was found to be decreased in the study of 100 patients with RA regardless of whether traditional cardiovascular risk factors were also present. Cardiorespiratory fitness was linked to obesity and the metabolic syndrome.