Secukinumab In Patients With Psoriatic Arthritis And Axial Manifestations: Predictors Of Response From The Double-Blind, Randomised, Phase 3b Maximise Trial

Abstract Background/Aims Psoriatic arthritis (PsA) is a heterogeneous disease with variability of response to different therapeutic modalities. Identifying potential demographic and disease characteristics as predictors of treatment response may define personalised treatment optimisation strategies. This post-hoc exploratory analysis of the MAXIMISE trial investigated the differential treatment effect of demographics and baseline characteristics as predictive factors in biologic-naïve patients with active PsA and symptoms of active spinal disease. Methods Full analysis set (FAS) comprised all patients from the randomised set assigned to study treatment, fulfilling the predefined clinical criteria for active axial disease, and for whom Assessment in Ankylosing Spondylitis 20% improvement criteria (ASAS20) data were available at week 12. The research hypothesis was that the odds ratio associated with the effect of treatment on ASAS20 responder status at week 12 would be different depending on 12 pre-specified predictor variables. A logistic regression model was initially fitted to the FAS that included 12 pre-specified covariates. A second logistic regression model was then fitted to the FAS that allowed for all 12 pre-specified variables to interact with treatment. The log-likelihood of the two fitted models were compared using a likelihood ratio test at a pre-specified significance level of 20% (i.e. P-value ≤0.20) to test whether any of the predefined variables interacted with treatment. If the above test was statistically significant at the 20% level, the variables of the second model were formally examined to determine whether overall effect of treatment was not applicable. Hypothesis tests were employed to determine the strength of evidence for each individual variable. Results The likelihood ratio test provided evidence against the assumption that overall effect of treatment is applicable to all patients (P-value, 0.08). Notably, the odds of being an ASAS20 responder if nail dystrophy is present at baseline were 3 times greater in the secukinumab 150-mg group and 5 times greater in the 300-mg group versus placebo (interaction P-value, 0.029). Although males fared worse than females in the placebo group, in the secukinumab 150-mg and 300-mg groups the odds of being a responder were similar to females (interaction P-value, 0.039). Current smokers were less likely to be ASAS20 responders versus never-smokers regardless of treatment group (interaction P-value, 0.589). Age, C-reactive protein level, Berlin MRI spine/SIJ score, time since first axial signs, number of swollen joints, new bone formation, and body mass index did not show a differential treatment effect on ASAS20 responses. Conclusion Of the 12 baseline variables of a unique population of 473 PsA patients with active axial disease diagnosed by clinical criteria, our analyses showed evidence of differential treatment effect, most notably for nail dystrophy, suggesting that the presence of nail dystrophy may predict a better response to secukinumab in PsA patients with axial manifestations. Disclosure L.C. Coates: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Amgen, Biogen, Medac, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, Novartis. X. Baraliakos: Consultancies; AbbVie, BMS, Celgene, Chugai, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Novartis. E. Pournara: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. L. Gossec: Consultancies; AbbVie, Amgen, BMS, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB. Grants/research support; Amgen, Galapagos, Lilly, Pfizer, Sandoz, Sanofi. H. Marzo-Ortega: Consultancies; Janssen, Novartis, AbbVie, Celgene, Lilly, Pfizer, Takeda, UCB. Member of speakers’ bureau; AbbVie, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Takeda, UCB. Grants/research support; Janssen, Novartis, AbbVie, Celgene, Lilly, Pfizer, UCB. P.J. Mease: Consultancies; AbbVie, Amgen, BMS, Boehringer Ingelheim, Galapagos, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, SUN Pharma, UCB. Member of speakers’ bureau; AbbVie, Amgen, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Lilly, Novartis, Pfizer, SUN, UCB. R. White: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. E. O'brien: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. B. Schulz: Other; Employee of Novartis.