Research report: Obesity and Early Biologic Failure in Psoriasis: An Italian Multicentre Retrospective Cohort Study

People with obesity who start biologic therapy for plaque psoriasis face roughly triple the risk of the treatment failing right from the start, according to a large retrospective cohort study conducted across five dermatology centres in the Veneto region of Italy. The research, published in Dermatology and Therapy, analysed 573 patients who together contributed 770 separate biologic treatment courses, and found that obesity was linked specifically to primary failure — the failure to achieve an adequate clinical response during the initial induction period — rather than to later loss of effectiveness or to safety-related withdrawal.

The numbers behind the headline finding are stark. Primary failure occurred in 17.0% of treatment lines from patients with obesity, defined as a body mass index of 30 kg/m2 or higher, compared with just 5.8% of treatment lines from patients without obesity. Kaplan-Meier survival analysis confirmed the difference was highly significant, with a log-rank p value below 0.001. In an adjusted Cox proportional hazards model controlling for age, sex, smoking status, psoriatic arthritis, previous biologic exposure, therapeutic class and baseline disease severity measured by the Psoriasis Area and Severity Index, obesity remained independently associated with a higher risk of primary failure, with a hazard ratio of 2.75 and a 95% confidence interval of 1.59 to 4.77.

The relationship extended beyond the simple obese versus non-obese dichotomy. When body mass index was modelled as a continuous variable scaled per 5 kg/m2 increase, each increment of that size was associated with a 37% higher risk of primary failure (hazard ratio 1.37, 95% confidence interval 1.14 to 1.65). An exploratory analysis using a natural cubic spline suggested the association was not strictly linear; a likelihood ratio test comparing the spline model with the linear model supported non-linearity, with a p value of 0.0018. A logistic regression treating primary failure as a binary endpoint produced a consistent result, with an adjusted odds ratio of 3.10 (95% confidence interval 1.69 to 5.69), and a sensitivity analysis excluding baseline disease severity from the model strengthened rather than weakened the obesity association.

Notably, the pattern was specific to early failure. Secondary failure — discontinuation due to loss of effectiveness after an initial response — occurred at similar rates in both groups, affecting 22.7% of treatment lines in patients with obesity and 20.9% in those without, and the adjusted analysis found no significant association (hazard ratio 1.15, 95% confidence interval 0.81 to 1.64). Safety-related discontinuation was rare overall, with only 15 events among 670 evaluable treatment lines, and no significant link with obesity emerged. All-cause discontinuation showed a weaker association with obesity than primary failure did, with a hazard ratio of 1.33 (95% confidence interval 1.03 to 1.71), and median all-cause drug survival was shorter in patients with obesity at 1900 days versus 3263 days.

The choice of biologic class mattered considerably. Among patients with obesity, primary failure rates differed sharply by mechanism of action: 33.3% of TNF-α inhibitor treatment lines failed primarily, compared with 9.5% of IL-17 inhibitor lines and 11.5% of IL-23 pathway inhibitor lines, a difference that was statistically significant (log-rank p = 0.003). In patients without obesity the corresponding rates were 10.0%, 4.4% and 3.6%, showing only a non-significant trend. In the adjusted Cox model, both IL-17 inhibitors (hazard ratio 0.49, 95% confidence interval 0.24 to 0.97) and IL-23 pathway inhibitors (hazard ratio 0.47, 95% confidence interval 0.24 to 0.93) were associated with lower primary failure risk than TNF-α inhibitors.

The study’s authors and related literature point to pharmacokinetics as a plausible explanation. Higher body weight increases the volume of distribution and clearance of monoclonal antibodies, which lowers serum drug concentrations under fixed-dose regimens. Pharmacokinetic analyses of ustekinumab, for example, have shown lower circulating concentrations with increasing weight, with particularly low levels in the highest-weight categories and levels becoming undetectable in some patients above 120 to 130 kg. Similar weight-exposure relationships have been described for fixed-dose IL-17 inhibitors such as secukinumab. Because many biologics are dosed without weight adjustment, heavier patients may simply receive proportionally less drug.

Inflammation may compound the dosing problem. Obesity is associated with a higher inflammatory burden, including elevated circulating TNF-α, IL-6, leptin and other adipokines, and a more active Th17/IL-23 axis, which could reduce treatment effectiveness. A comparative study of 200 adults reported higher serum TNF-α concentrations in participants with overweight or obesity than in controls, with the highest levels in patients with obesity and metabolic syndrome, and TNF-α correlated with body mass index and metabolic parameters. This convergence of lower drug exposure and higher inflammatory drive may explain why TNF-α inhibitors showed the highest primary failure rates among patients with obesity in the Italian cohort.

External evidence supports the dose-response pattern. In the BIOBADADERM prospective registry, each 5-unit increase in body mass index was associated with a higher risk of lack of effectiveness, with a hazard ratio of 1.12 (95% confidence interval 1.01 to 1.24), irrespective of the drug used. A cross-disease meta-analysis of 54 cohorts including 19,372 patients treated with anti-TNF agents found that obesity was associated with higher odds of treatment failure (odds ratio 1.60, 95% confidence interval 1.39 to 1.83), with a similar effect in the psoriasis and psoriatic arthritis subgroup. A recent case-control study reported that a body mass index of 25 kg/m2 or higher was the only factor associated with early loss of efficacy of a first biologic leading to switching within 24 months, and transcriptomic analysis of pretreatment lesional biopsies from those patients revealed an epidermis-centred innate and neutrophil inflammatory pattern.

The new study has limitations that temper causal interpretation. As an observational, retrospective analysis of routine clinical data, it cannot prove that obesity causes biologic failure, and prescribing patterns and drug availability changed over the study period. Analyses were performed at the treatment-line level, meaning patients could contribute multiple courses; cluster-robust models addressing within-patient correlation left the obesity association essentially unchanged (hazard ratio 2.75, robust 95% confidence interval 1.58 to 4.81), but residual dependence cannot be excluded. Drug levels, weight change over time and standardised response measures such as PASI90 or PASI100 at fixed timepoints were not available, and the rarity of safety discontinuations left those comparisons underpowered.

Even so, the specificity of the finding carries practical weight. Obesity in this cohort was common — 193 of 562 patients with available body mass index data, or 34.3%, met the threshold — and patients with obesity also had markedly higher rates of hypertension, diabetes and dyslipidemia, though their age, sex distribution, psoriatic arthritis prevalence and prior biologic exposure were similar to those of patients without obesity.

Subject of Research: The association between obesity and early biologic treatment failure in plaque psoriasis

Article Title: Obesity and Early Biologic Failure in Psoriasis: An Italian Multicentre Retrospective Cohort Study

Article References: Tartaglia, J., Donini, M., Garbo, C., Gatti, A., Gisondi, P., Romagnolo, N., Schiesari, L., & Piaserico, S. (2026). Obesity and Early Biologic Failure in Psoriasis: An Italian Multicentre Retrospective Cohort Study. Dermatology and Therapy. https://doi.org/10.1007/s13555-026-01956-y

Image Credits: AI Generated

DOI: 10.1007/s13555-026-01956-y

Keywords: psoriasis, obesity, biologics, primary failure, TNF-α inhibitors, drug survival, body mass index, IL-17 inhibitors, IL-23 inhibitors, retrospective cohort study, pharmacokinetics, dermatology