P262 Guselkumab, an anti-interleukin-23p19 monoclonal antibody, in patients with active PsA who were biologic-naïve or prior TNFα inhibitor-treated: week 24 results of a Phase 3, randomised, double-blind, placebo-controlled study
Authors: Deodhar Atul , Helliwell Philip , Boehncke Wolf-Henning , Hsia Elizabeth C , Kollmeier Alexa P , Subramanian Ramanand A , Xu Xie L , Sheng Shihong , Zhou Bei , Gorecki Patricia C , Ritchlin Christopher 
Published: April 2020

Abstract

Background
Guselkumab (GUS), an anti-interleukin-23p19 monoclonal antibody, is approved to treat psoriasis (PsO). We evaluated GUS efficacy and safety in a Phase 3, double-blind, placebo (PBO)-controlled trial in patients with active PsA who were biologic-naïve or prior TNFα inhibitor (TNFi)-treated (DISCOVER-1).

Methods
Adults with active PsA (≥3 swollen + ≥3 tender joints; CRP ≥0.3mg/dL) despite standard therapies (eg, non-biologic DMARDs, apremilast, or NSAIDs) were eligible. ∼30% of patients previously could have received or have had inadequate response to 1-2 TNFi. Patients were randomised 1:1:1, stratified by Week [W]0 DMARD use and prior TNFi use, to GUS 100mg Q4W; GUS 100mg at W0, W4, Q8W (Q8W); or PBO. Concomitant stable use of select non-biologic DMARDs, oral corticosteroids, and NSAIDs was allowed. At W16, patients with &lt;5% improvement in tender+swollen joints could initiate or increase the dose of permitted medications while continuing study treatment. The primary endpoint was ACR20 at W24. Major secondary endpoints included: Investigator’s Global Assessment (IGA) PsO response (IGA=0/1 + ≥2-grade reduction) at W24 in patients with ≥3% BSA PsO and IGA ≥2 at W0; changes in DAS28-CRP, HAQ-DI and SF-36 PCS scores and ACR50/70 response at W24; and ACR20/50 response at W16. As preplanned, enthesitis or dactylitis data were pooled with those from the companion Phase 3 study DISCOVER-2. Due to different regional health authority regulatory requirements, Global and US multiplicity control procedures were prespecified with statistical results from US procedures presented. Unadjusted (nominal) p-values are provided for other endpoints. Adverse events (AEs) through W24 are reported.

Results
381 patients were treated and analyzed; baseline characteristics were consistent with moderate-to-severe disease (mean BSA involved with PsO: 13.4%, patients with IGA=3-4: 42.5%; mean swollen/tender joint counts: 9.8/19.3). Significantly more patients receiving GUS Q4W (58.6%) and Q8W (52.8%) vs PBO (22.2%, both p &lt; 0.001) achieved ACR20 response at W24. Consistent response rates were observed in the subgroups of patients with or without prior TNFi use. Significantly greater improvements in HAQ-DI and SF-36 PCS scores were seen in GUS- vs PBO-treated patients from W0 to W24. Among 249 patients with ≥3% BSA PsO and IGA ≥2 at W0, significantly more GUS- vs PBO-treated patients achieved IGA response. Higher proportions of patients achieved ACR20 response at W16, ACR50 response at W16/24, ACR70 response at W24, and PASI75/90/100 responses at W24. More GUS Q4W- or Q8W- vs PBO-treated patients achieved MDA response at W24. Serious AEs, serious infections, and death occurred in 9/381 (2.4%), 2/381 (0.5%), and 1/381 (0.3%) patients, respectively.

Conclusion
In patients with active PsA who were biologic-naïve or had been treated with TNFi, both GUS Q4W and Q8W demonstrated efficacy for joint and skin symptoms, physical function, and quality of life relative to PBO. Observed AEs were consistent with GUS safety established in PsO.

Disclosures
A. Deodhar: Other; A.D. has been a study investigator for Janssen clinical trials. P. Helliwell: Other; P.H. has been a research investigator for Janssen. W. Boehncke: Other; W.B. has been a study investigator for Janssen. E.C. Hsia: Other; E.H. is a Janssen employee. A.P. Kollmeier: Other; A.K. is a Janssen employee. R.A. Subramanian: Other; R.S. is a Janssen employee. X.L. Xu: Other; X.X. is a Janssen employee. S. Sheng: Other; S.S. is a Janssen employee. B. Zhou: Other; B.Z. is a Janssen employee. P.C. Gorecki: Other; P.G. is a Janssen employee. C. Ritchlin: Other; C.R. has been a study investigator for Janssen.