Original articleObesity reduces the drug survival of second line biological drugs following a first TNF-α inhibitor in rheumatoid arthritis patients
Introduction
There is emerging evidence that obesity is a low-grade inflammatory status characterized by increase in pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α interleukin-6 (IL-6) and overexpression of specific adipocyte derived adipokines released by the visceral fat, and its relationships with joint diseases are only partially unraveled [1]. Unlike psoriatic arthritis (PsA) whose incidence in obese people has been found to be increased [2], the association of obesity and rheumatoid arthritis (RA) is controversial as a correlation with the body mass index (BMI) [2] or a modest risk to develop RA has been reported [3]. Obesity, however, can impact on the natural history of RA and its response to therapy. The relationships with activity and evolution of the disease are somewhat puzzling. A higher disease activity, assessed by the 28-joint Disease Activity Score (DAS28), has been found in obese RA patients in some cohorts [4], but not in others [5], [6]. Nevertheless, the apparent paradox is that obesity may hamper the evolution of bone erosions as BMI was inversely correlated with joint damage in longitudinal study of RA patients with either early or established disease. Patients with recent onset RA and low BMI had higher radiographic joint damage than those with normal or high BMI [7], and obese RA patients showed less progression of bone reabsorption than normal-weight patients at 2 or 3 years [8], [9], [10]. This protective effect of high BMI on bone might be directly related to the imbalance between leptin and adiponectin produced by visceral adipose tissue [11], [12].
Another emerging issue is the poor response of RA patients with high BMI to anti-TNF-α drugs, as observed for etanercept or adalimumab given at fixed dosage regimen, as well as infliximab, which is administrated per body weight [5], [13]. In a prospective study, the obese RA patients showed a significantly lower percentage of good European League Against Rheumatism (EULAR) response than normal-weight patients after 16 weeks of therapy with infliximab [13]. Furthermore, a 12 months survey on RA patients upon anti-TNF-α drugs has provided evidence that it was double the percentage of normal-weight subjects achieving a DAS28-based remission as compared to obese patients [5]. More recently, a lower probability to achieve good clinical outcomes in obese RA patients with early [14] or established disease has been also reported [15].
To our knowledge, there are no data on the clinical outcomes of the administration of a biological drug to RA obese patients after failure of anti-TNF-α agents. The endpoint of this study was to evaluate the drug survival and clinical responses to a second line biological drug in obese patients with RA.
Section snippets
Patients
Two hundred and ninety-two patients with RA were retrospectively selected from the local longitudinal database. The local ethics committee (Azienda Policlinico, Bari) has approved the register and prior written informed consent to take part was obtained from all patients in compliance with the Helsinki Declaration. RA was diagnosed according to the 1987 ACR revised criteria [16] and patients having active disease began a treatment with a biological drug after inadequate response to one or more
Patients demographics at baseline
Out of 292 RA patients starting a first ever anti-TNF-α drug and available BMI were analyzed (117 normal-weight, 109 overweight, and 66 obese). Overall, median DAS28 was 5.6 and did not significantly differ among the three groups. Nor did the years of disease, the functional ability assessed by HAQ, smoking status, and the presence of RF or ACPA. Normal-weight patients were significantly younger than overweight or obese patients (P = 0.03), and took less glucocorticoids or DMARDs than overweight
Discussion
In this study, we evaluated the clinical outcomes in obese RA patients undergoing treatment with biological drugs because of their active disease. This study provides evidence to show that obesity may affect the clinical response both to a first TNF-α inhibitor and to a subsequent non-anti-TNF-α drug.
It is well-established that the outcomes of RA can be affected by comorbidities, including obesity. White fat tissue is a source of pro-inflammatory and regulatory cytokines, the homeostasis
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
Funding: This work has not received financial support.
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