LONDON (FRONTLINE MEDICAL NEWS) – Patients with psoriatic arthritis appear less likely to achieve a good response to their first anti–tumor necrosis factor (anti-TNF) therapy if they are obese, according to data taken from two Nordic registries.
In a large observational cohort study, obese individuals with psoriatic arthritis (PsA) were significantly less likely than their nonobese counterparts to achieve a European League Against Rheumatism (EULAR) good or moderate response at 6 months (55% vs. 65%, P = .02). The overall odds ratio for achieving a good or moderate response was 0.47 when comparing obese with nonobese individuals.
The findings are potentially important because, with the exception of infliximab, anti-TNF therapy is not currently adjusted according to body weight, said presenting study author Pil Højgaard in an interview at the European Congress of Rheumatology.
Ms. Højgaard, who is an M.D. Ph.D. student at the department of rheumatology, Copenhagen University Hospital Gentofte, Rigshospitalet and the Parker Institute in Copenhagen, noted that obesity was a frequent comorbid condition in patients with PsA and that it is a known proinflammatory condition. As such, obesity could potentially affect immunologic processes, the pharmacokinetics of treatments, and ultimately patient outcomes.
Since TNF-alpha inhibitor (TNFi) treatment fails in around half of all patients with PsA treated in routine care, Ms. Højgaard noted that the aim of the cohort study was to investigate whether obesity could be having any influence on this.
Data on baseline characteristics, EULAR response rates, and drug adherence were obtained for 1,943 patients with PsA prescribed their anti-TNF therapy from two nationwide registries of disease-modifying therapies being used to treat rheumatic conditions in Denmark and Iceland, DANBIO ( Rheumatology. 2011;50:69–77 ) and ICEBIO, respectively.
At baseline, body mass index (BMI) data were available for 1,271 patients and 408 (32%) of these had a BMI of 30 kg/m2 or more and were classed as being obese. The majority (39%) had received a first prescription for adalimumab, with around a quarter each prescribed etanercept (26%) or infliximab (24%), and the remainder prescribed golimumab (7%) and certolizumab (4%).
Compared to the 863 (68%) nonobese individuals, the obese patients were older (47 vs. 49 years, P = .01), less likely to smoke (30% vs. 23%, P = .01), and had higher disease activity measured on the Disease Activity Score 28 (DAS28) (4.4 vs. 4.6, P = .01). Health Assessment Questionnaire scores were also higher in obese than in nonobese individuals (1.1 vs. 0.9, P less than .01), and there were higher tender joint counts (6 vs. 5, P = .01), and higher pain levels assessed on a visual analog scale (VAS). Obese patients also had higher scores on a VAS patient global scale. The median follow-up time was 1.5 years.
Patients who were obese were found to adhere to TNFi treatment for shorter periods of time than nonobese patients, with median durations of 1.76 and 3.08 years, respectively (P less than .001). This discrepancy was most pronounced among men, a finding that may account for the fact that they were less likely to achieve a good EULAR response than their nonobese counterparts (OR = 0.5).
Being obese versus not being obese independently predicted TNFi withdrawal overall (hazard ratio, 1.6), especially in men (HR, 1.8; HR, 1.5 in women). TNFi withdrawal was more likely in obese than in nonobese patients even when individual treatments were considered; adalimumab: HR, 1.6; etanercept: HR, 2.0; infliximab: HR, 1.6.
An association between obesity and reduced response to anti-TNF therapy has also been observed in patients with rheumatoid arthritis, Ms. Højgaard acknowledged. There have also been a few studies of PsA and psoriasis “but to my knowledge, I think in the field of psoriatic arthritis, we are one of the few that have been looking at long-time drug survival,” she said. “We also include quite a lot of patients.”
“Of course this is not a randomized clinical study, so there could be residual confounding factors,” Ms. Højgaard cautioned. “It is always a bit difficult to say something about causality when it is a database study,” she added. “I think what we can see here is that there is an association, but in order to recommend weight loss we need some prospective studies.”
She noted that there was one published clinical study ( Ann Rheum Dis. 2014;73:1157–62 ) that had looked at the benefit of a weight reduction program started at the same time as TNFi initiation in patients with PsA. This found there was a benefit of weight loss on response to TNFis, regardless of the type of diet.
DANBIO is supported by unrestricted grants from Abbott, Pfizer, MSD, Bristol-Myers Squibb, Roche, and UCB-Nordic. The sponsors have had no influence on data collection, analysis, or publication. ICEBIO is part of the electronic medical record system held by the University of Reykjavik and receives no industrial funding. Ms. Højgaard has received speaking fees from Celgene and UCB not related to this work.