Abstract
Introduction: Guselkumab effectively treats psoriasis and is associated with improvements in anxiety and depression symptoms. Whether improvements in anxiety and depression are due to resolution of skin symptoms or the direct result of guselkumab treatment is unclear. Methods: Patients received guselkumab at Week(W)0, W4, then Q8W; placebo (W16→guselkumab); or adalimumab for moderate-to-severe psoriasis. Mediation analysis evaluated direct effects of guselkumab on change from baseline in Hospital Anxiety and Depression Scale (HADS) score at W24, after adjusting for indirect effects mediated by clinical assessment of skin clearance using Psoriasis Area and Severity Index (PASI) improvement and achievement of ≥90% improvement from baseline (PASI90). Regression analyses were used to determine 95% confidence interval (CI). Results: Improvements in HADS were partially mediated indirectly through skin response among guselkumab-treated patients at W24. Compared with adalimumab, HADS anxiety score was mediated through PASI improvement by 25.5%, with independent treatment effect of -0.74 (95% CI -1.22,-0.27; P < .002), or 74.5% of total effect. Similarly, treatment effect was mediated by 24% through PASI90 response, with independent treatment effect of -0.76 (95% CI -1.24, -0.28; P < .002), or 76% of total effect. Treatment effect of guselkumab (versus adalimumab) on change in HADS depression total score was mediated through PASI improvement by 49.8%; through PASI90, 40.5%. Guselkumab and adalimumab had similar natural direct effects on changes in depression score. Conclusions: Guselkumab demonstrated an independent treatment response in reducing anxiety and depression after adjusting for clinical response of skin clearance. The mechanism of the direct effect of guselkumab beyond skin clearance warrants additional research.
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