Long-Term Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19 Subunit of Interleukin-23, Through Two Years: Results From a Phase III, Randomized, Double-Blind, Placebo-Controlled Study Conducted in Biologic-Naive Patients With Active Psoriatic Arthritis

Abstract

Objective: To assess long-term efficacy and safety of guselkumab, an interleukin-23 p19 subunit (IL-23p19) inhibitor, in patients with active psoriatic arthritis (PsA) from the phase III DISCOVER-2 trial.

Methods: In the DISCOVER-2 trial, patients with active PsA (≥5 swollen joints and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite prior nonbiologic therapy were randomized to receive the following: guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks; or placebo with crossover to guselkumab 100 mg every 4 weeks, beginning at week 24. Efficacy assessments included American College of Rheumatology ≥20%/50%/70% improvement criteria (ACR20/50/70), Investigator's Global Assessment (IGA) of psoriasis score of 0 (indicating complete skin clearance), resolution of enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score), and changes in the Sharp/van der Heijde modified radiographic scores for PsA. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through week 100; safety assessments continued through week 112.

Results: Of the 739 randomized and treated patients, 652 (88%) completed treatment through week 100. Across groups of guselkumab-treated patients (including those in the placebo-guselkumab crossover group), the following findings at week 100 indicated that amelioration of arthritis signs/symptoms and extraarticular manifestations was durable through 2 years: ACR20 response (68-76%), ACR50 response (48-56%), ACR70 response (30-36%), IGA score of 0 (55-67%), enthesitis resolution (62-70%), and dactylitis resolution (72-83%). Mean changes in the Sharp/van der Heijde modified score for PsA from weeks 52 to week 100 (range 0.13-0.75) indicated that the low rates of radiographic progression observed among guselkumab-treated patients at earlier time points extended through week 100. Through week 112, 8% (5.8 per 100 patient-years) and 3% (1.9 per 100 patient-years) of the 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; 1 death occurred (road traffic accident).

Conclusion: In biologic-naive PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2 years.

Figure 1

Proportions of patients achieving American College of Rheumatology ≥20% improvement criteria (ACR20) (A and B), ACR50 (C and D), and ACR70 (E and F) responses through week 100. Response rates derived using nonresponder imputation (NRI) for missing data (see Patients and Methods) are shown in panels A, C, and E; response rates from weeks 24–100 derived from observed data are shown in panels B, D, and F. The dashed vertical line at week 24 indicates placebo (PBO) crossover to guselkumab (GUS) administered every 4 weeks (Q4W); gray shading indicates post hoc NRI data. Q8W = every 8 weeks.

Figure 2

Cumulative probability plot of observed changes in Sharp/van der Heijde modified scores for psoriatic arthritis (PsA‐modified vdH‐S), from baseline to week 100, in patients randomized to receive guselkumab every 4 weeks (Q4W) (A) or every 8 weeks (Q8W) (B). SDC = smallest detectable change.

Figure 3

Proportions of patients achieving Investigator’s Global Assessment (IGA) 0/1 response (A), ≥90% improvement in the Psoriasis Area and Severity Index (PASI90) response (B), IGA score 0 (C), and PASI100 response (D) through week 100 (W100). IGA and PASI scores were assessed in patients with ≥3% body surface area with psoriasis involvement and an IGA score of ≥2 at baseline. Response rates were derived using NRI for missing data. IGA response was defined as score of 0/1 and ≥2‐grade improvement. See Figure 1 for other definitions.

Figure 4

Proportions of patients maintaining ACR20, ACR50, or ACR70 responses or minimal disease activity (MDA) at week 100 among those who achieved these responses at week 52. Response rates were derived using NRI for missing data. See Figure 1 for other definitions.