Obesity May Influence Biologic Response in PsO, With Effects Varying by Drug Class

Obesity, a common metabolic comorbidity of psoriasis closely linked to persistent low‑grade inflammation, may reduce the likelihood of achieving optimal responses to biologic therapy, although the magnitude of that effect appears to differ by biologic class and should be interpreted cautiously.¹ A new systematic review and meta-analysis of 12 studies involving 4,200 patients found lower treatment response rates among obese patients across multiple Psoriasis Area and Severity Index (PASI) endpoints, while emphasizing that current evidence does not support selecting a biologic solely based on a patient's weight.²

Meta-Analysis Overview

The analysis included data from randomized controlled trials and observational studies published through March 2026. Investigators evaluated the impact of obesity on treatment response across tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17, IL-23, and IL-12/23 inhibitors. The primary endpoint was PASI90, with PASI75 and PASI100 analyzed as secondary outcomes.

The review incorporated 2 randomized controlled trials and 10 observational studies conducted across Europe, Asia, North America, and multinational cohorts. Most included patients had moderate-to-severe plaque psoriasis, with obesity prevalence ranging from 16.7% to 48.1%. Overall study quality was considered generally high.

Impact of Obesity on Efficacy Endpoints

Across 17 comparisons from 9 studies, obese patients were less likely than non-obese patients to achieve PASI90, with a pooled relative risk (RR) of 0.64 (95% CI, 0.55-0.76). However, investigators detected significant publication bias, and after applying a trim-and-fill correction, the association was no longer statistically significant (RR, 0.79; 95% CI, 0.58-1.08). The authors cautioned that the PASI90 findings should therefore be interpreted carefully.

More consistent differences were observed for the secondary efficacy endpoints. In pooled analyses, obese patients were significantly less likely to achieve PASI75 (RR, 0.52; 95% CI, 0.34-0.80) and PASI100 (RR, 0.42; 95% CI, 0.31-0.58). Unlike the PASI90 analysis, these findings remained robust after correction for publication bias or showed no evidence of publication bias.

Key Modifying Factors

Subgroup analyses suggested that the effect of obesity may vary by biologic class. Reduced PASI90 responses were observed among patients treated with IL-17 inhibitors (RR, 0.57) and IL-12/23 inhibitors (RR, 0.43). By contrast, obesity was not associated with a statistically significant reduction in PASI90 among patients receiving TNF-α or IL-23 inhibitors. However, the investigators emphasized that these subgroup findings were based on a limited number of studies, particularly for TNF-α and IL-23 inhibitors, and should not be interpreted as evidence that those drug classes are unaffected by obesity.

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Treatment duration also appeared to influence outcomes. The negative effect of obesity on PASI90 was greatest during the first 16 weeks of therapy, became less pronounced at 48 to 52 weeks, and remained significant again in studies with follow-up of 90 weeks or longer. Meta-regression identified biologic class, study design, geographic region, mean body mass index (BMI), and the proportion of obese participants as significant contributors to heterogeneity, while follow-up duration was not.

Underlying Mechanisms and Geographic Variations

Several factors may explain the observed variability. The authors noted that obesity is associated with chronic low-grade inflammation, with adipose tissue producing cytokines including TNF-α, IL-6, and IL-17 that may influence psoriasis pathogenesis. Obesity may also alter the pharmacokinetics of biologic therapies by changing drug distribution and clearance. At the same time, differences in study design, obesity definitions, baseline disease severity, and prior biologic exposure likely contributed to the heterogeneity across studies.

The investigators also noted regional differences. The apparent negative impact of obesity on PASI90 was stronger in Asian studies than in Western studies. However, they emphasized that differences in BMI cutoffs used to define obesity, along with the predominance of Chinese cohorts and shorter follow-up in the Asian studies, make these findings hypothesis-generating rather than definitive.

Clinical Implications

Despite the observed associations, the investigators caution against using obesity alone to guide biologic selection. Instead, weight status should be considered alongside other clinical factors when developing individualized treatment plans. The authors also highlighted the need for prospective studies using standardized definitions of obesity and individual patient-level data to better define the relationship between body weight and biologic effectiveness across different therapeutic classes.

References

1. Lafuente-Urrez RF, Pérez-Pelegay J. Impact of obesity on the effectiveness of adalimumab for the treatment of psoriasis: a retrospective study of 30 patients in daily practice. Eur J Dermatol. 2014;24(2):217-223. doi:10.1684/ejd.2014.2278

2. Zhou W, Xu Z, Yu H, Wang X, Li L, Pan X. Efficacy differences of biologic agents targeting different pathways in obese patients with psoriasis: a systematic review and meta-analysis. J Dermatolog Treat. 2026;37(1):2705161. doi:10.1080/09546634.2026.2705161