X. Liu1, P. Branigan1, Y. Chen1, B. Scott1, M. Banaszewska1, P. McGovern1, Z. Yao1, S. Li1, Y. Wasfi1, M. Song1, K. Campbell1, E. Munoz-Elias1
Introduction and Objectives: VOYAGE 2 is a phase 3 study that evaluated the efficacy of guselkumab (GUS) in psoriasis patients during treatment, treatment withdrawal and subsequent retreatment (following loss of PASI 90). We report biomarker and clinical parameters associated with response.
Material and Methods: Serum cytokines were measured via Singulex (IL-17A, IL-17F and IL-22) or Meso Scale Discovery (MIP1β, MDC and IL-8) platforms. Clinical parameters evaluated included: disease duration, body mass index (BMI), Week 28 Investigator’s Global Assessment (IGA), and GUS blood concentration at Week 28. Associations were evaluated by Welch’s t test or Fisher’s exact test. Predictive models were built using multivariate logistic regression and evaluated by area under the curve (AUC) of the receiver operating characteristic curve.
Results: Long-term maintenance of PASI90 response following drug withdrawal was associated with shorter disease duration (p<0.005), lower BMI (p<0.001), lower levels of serum IL17F (p<0.03) and MIP1β (p<0.02) at baseline, achieving IGA 0 at WK28 (p<0.001), and higher GUS concentration at WK28 (p<1E-07). Predictive models were built which showed individual and combinations of parameters had low/moderate predictive power for response maintenance. A model combining disease duration, IGA 0 response and GUS concentration at WK28 had AUC of 0.83 and 0.74 in the training and validation sets, respectively. Conclusions GUS exhibits long-term maintenance of PASI90 response following withdrawal of treatment in a subset of patients. Shorter disease duration, lower levels of baseline, higher drug concentration and achieving complete skin clearance at WK28 were associated with this response.