Obesity poses a dual challenge in inflammatory arthritis: it increases disease risk and reduces treatment effectiveness. Studies show that obesity is independently linked to higher disease activity and weaker response to biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs). The clinical impact is significant. While 30–50% of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients fail to achieve sustained remission, this rate rises to 60–70% among patients with obesity (1). Approximately 1.5 million adults in Europe and North America have RA or PsA, and roughly half also have obesity—meaning around 600,000 patients face this combined therapeutic challenge. With obesity prevalence projected to triple by 2050, the consequences for patient outcomes and healthcare costs are profound (2).
However, the relationship between obesity and treatment response demonstrates considerable heterogeneity across disease entities and therapeutic agents, revealing a complex immunometabolic interplay. In RA, obesity reduces the probability of achieving remission by 40–60%, with this effect most pronounced in anti-citrullinated protein antibody (ACPA)-positive disease (3). For tumor necrosis factor inhibitors (TNFi) specifically, the therapeutic disparity is remarkable: remission rates of 35% in patients with obesity compared to 72% in normal-weight patients have been documented (4). PsA exhibits comparable patterns, with multiple observational studies demonstrating significantly diminished remission rates in the context of obesity. Consequently, both RA and PsA patients with obesity experience higher rates of treatment switching and serial biologic exposure (5).
Gout represents a distinct but parallel paradigm in which obesity compromises therapeutic outcomes. Beyond established associations with metabolic syndrome, obesity directly impairs urate-lowering therapy (ULT) efficacy. In the case of febuxostat, patients with obesity achieve target serum urate levels in only 40% of cases, compared with 65% in normal-weight patients (6). This phenomenon is attributable to multifactorial pharmacokinetic alterations: increased body weight expands drug volume of distribution, enhances renal clearance, and consequently reduces therapeutic drug concentrations at target tissues.
Understanding the mechanisms underlying obesity-mediated treatment resistance in inflammatory arthritis will be essential for developing targeted interventions that can bridge this therapeutic gap.
Dr. Hannah den Braanker Rheumatology resident and post-doctoral researcher at Maasstad Hospital and Erasmus Medical Centre, Rotterdam, The Netherlands EMEUNET Newsletter Sub-committee member
References
- den Braanker H, van der Valk E.S, Bisoendial R.J. A Lymphatic Perspective on Obesity and Inflammatory Arthritis: New Disease-Modifying Potential in Rheumatology. J. Clin. Med. 2025, 14, 7641. https://doi.org/10.3390/jcm14217641
- GBD 2021 Adult BMI Collaborators. Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: A forecasting study for the Global Burden of Disease Study 2021. Lancet 2025, 405, 813–838. doi: 10.1016/S0140-6736(25)01722-2.
- Hollander N.K.D, Boeren A.M.P, van der Helm-van Mil A.H.M, van Steenbergen H.W. Patients with obesity have more inflamed joints and higher CRP levels during the disease course in ACPA-positive RA but not in ACPA-negative RA. Arthritis Res. Ther. 2024, 26, 42. doi: 10.1186/s13075-023-03248-8.
- Novella-Navarro M, Genre F, Hernandez-Breijo B, Remuzgo-Martinez S, Martinez-Feito A, Peiteado D, Monjo I, Gonzalez-Gay M.A, Plasencia-Rodriguez C, Balsa A. Obesity and response to biological therapy in rheumatoid arthritis: The role of body mass index and adipose tissue cytokines. Clin. Exp. Rheumatol. 2022, 40, 1726–1732. doi: 10.55563/clinexprheumatol/a9gskx.
- Ogdie A, Palmer J.L, Greenberg J, Curtis J.R, Harrold L.R, Solomon D.H, Kavanaugh A, Kremer J.M, Mease P.J. Predictors of Achieving Remission among Patients with Psoriatic Arthritis Initiating a Tumor Necrosis Factor Inhibitor. J. Rheumatol. 2019, 46, 475–482. doi: 10.3899/jrheum.171034.
- Cheng Z, Xu X, Qi H, Li X, Li Y, Jiang C, Miao X, Ji X, Wang Y, Dong B, Li C, Lu J. Obesity reduces the urate-lowering efficacy among patients with primary gout: A prospective cohort study. Rheumatology 2025, 64, 3500–3508. doi: 10.1093/rheumatology/keaf076.