A large real-world study suggests obesity reduces the likelihood of reaching minimal disease activity in psoriatic arthritis, with the strongest effect seen in patients treated with fixed-dose TNF inhibitors.
Higher body mass index independently reduces the likelihood of achieving minimal disease activity in psoriatic arthritis, and the effect appears to be largely confined to patients treated with tumour necrosis factor inhibitors, according to a large longitudinal cohort study published in Rheumatology.
The Canadian study of 1291 patients found that every increase in BMI was associated with lower odds of reaching MDA after adjustment for age, sex, smoking, fibromyalgia, anxiety and depression, radiographic damage, and treatment type.
Importantly, the association appeared to be driven predominantly by worsening patient-reported outcomes rather than objective inflammatory measures.
The findings also suggest obesity may influence the effectiveness of fixed-dose TNF inhibitors more than other biologic or targeted synthetic DMARD classes, raising questions about treatment selection and the growing role of weight management alongside pharmacological therapy.
The researchers analysed data from the longstanding Gladman Krembil Psoriatic Arthritis Program in Toronto, which has prospectively followed patients since 1978.
The cohort included 1291 adults with a mean age of 44.7 years and a mean BMI of 28.8kg/m², placing the average participant in the overweight range.
A subgroup analysis evaluated 1102 treatment courses across TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors, IL-12/23 inhibitors, JAK inhibitors, and the PDE4 inhibitor apremilast.
Across the overall cohort, higher BMI remained significantly associated with lower odds of achieving MDA after multivariable adjustment, with an odds ratio of 0.97 for each one-unit increase in BMI.
Female sex, older age, smoking, fibromyalgia, and greater radiographic damage also independently reduced the likelihood of achieving MDA.
However, BMI did not affect every component of the composite outcome equally.
Higher BMI was associated with worse tender joint counts, enthesitis scores, psoriasis severity, pain, patient global assessment, and functional disability, but showed no significant association with swollen joint count.
The researchers said this pattern suggested obesity has a disproportionate impact on subjective disease measures and overall disease burden rather than simply increasing objective inflammatory activity.
When treatment class was examined, the most consistent finding involved TNF inhibitors.
Patients starting TNF inhibitors had significantly lower odds of achieving MDA as BMI increased, and this association persisted when BMI was analysed longitudinally throughout follow-up. The effect remained after excluding infliximab, the only weight-based TNF inhibitor included in the analysis.
In contrast, no statistically significant relationship between BMI and treatment response was seen for IL-17, IL-23, IL-12/23, or JAK inhibitors.
Apremilast was the only agent associated with improved odds of MDA at higher BMI, although the authors cautioned that this finding required confirmation.
The lack of association with infliximab may reflect the advantages of weight-based dosing, the researchers suggested.
Higher body weight can alter drug distribution and clearance, potentially reducing effective exposure with fixed-dose biologics, whereas infliximab dosing may partly compensate for these pharmacokinetic changes.
The researchers said their findings aligned with earlier observational studies linking obesity to poorer outcomes in psoriatic arthritis but extend previous work by examining newer therapeutic classes while accounting for time-varying BMI and multiple clinical confounders.
They noted that the apparent absence of BMI effects in non-TNF drug classes should be interpreted cautiously because patient numbers were considerably smaller, limiting statistical power.
Rheumatologists are increasingly considering weight-loss interventions as adjunctive therapy for inflammatory arthritis.
Related
Previous dietary intervention studies have shown that weight reduction can improve disease activity in obese patients with psoriatic arthritis, while emerging evidence suggests GLP-1 receptor agonists and dual GIP/GLP-1 agonists may improve pain and physical function in musculoskeletal disease in addition to producing substantial weight loss.
The researchers cited early evidence from the TOGETHER-PsA study suggesting combined ixekizumab and tirzepatide therapy may improve clinical outcomes alongside significant weight reduction.
Future studies should determine whether weight loss itself could improve treatment response across modern biologic classes and help distinguish improvements driven by reduced inflammation from those resulting from changes in pain perception and patient-reported outcomes, they said.
The researchers acknowledged several limitations, including the observational design, potential residual confounding, incomplete information on weight-modifying medications such as GLP-1 receptor agonists throughout follow-up, and relatively small numbers for newer biologic classes.
They also noted that BMI was an imperfect surrogate for adiposity and did not distinguish visceral fat from lean body mass, factors that may be more relevant to inflammatory burden.
“In conclusion, in this large PsA cohort, higher BMI was independently associated with lower odds of MDA state and worse outcomes across multiple disease domains. This was particularly evident in patients treated with TNFi,” they wrote.
“These findings suggest that obesity may be an important, modifiable factor in PsA management and underscore the need to integrate weight optimisation strategies alongside pharmacologic therapy.
“Further research is needed to investigate the possible role of weight reduction on long-term outcomes with newer therapeutic drug classes.”
