Efficacy and Safety of Guselkumab, an Interleukin‐23p19–Specific Monoclonal Antibody, Through One Year in Biologic‐Naive Patients With Psoriatic Arthritis

Abstract

Objective. Guselkumab, a human monoclonal antibody specific to interleukin-23p19, demonstrated efficacy and safety versus placebo through week 24 of the phase III DISCOVER-2 trial in biologic-naive patients with psoriatic arthritis (PsA). Here we report 1-year DISCOVER-2 findings. Methods. Adults with active PsA (≥5 swollen and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite standard nonbiologic treatment were randomized to receive subcutaneous injections of guselkumab 100 mg every 4 weeks, guselkumab 100 mg at week 0, week 4 and every 8 weeks thereafter, or placebo with crossover to guselkumab 100 mg every 4 weeks at week 24. We primarily evaluated clinical efficacy through week 52 by imputing missing data (nonresponse for categorical end points; no change/using multiple imputation for continuous end points). Observed radiographic scores and adverse events (AEs) were summarized. Results. Of 739 randomized, treated patients, 93% completed week 52. The proportions of patients in whom a ≥20% improvement from baseline in American College of Rheumatology criteria (ACR20) was achieved were maintained after week 24, reaching 71% (173 of 245) and 75% (185 of 248) for patients randomized to receive treatment every 4 weeks or every 8 weeks, respectively, by week 52. The proportions of patients in whom ACR50/ACR70 and skin responses, minimal or very low disease activity, and dactylitis or enthesitis resolution were achieved at week 24 were also maintained through week 52. Further, low levels of radiographic progression, along with improvements in physical function and health-related quality of life, were sustained through week 52 with continued guselkumab treatment. Few patients experienced serious infections through week 52, with no evidence of a dosing regimen response or increase from weeks 0-24 (4 of 493 [0.8%]) to weeks 24-52 (3 of 493 [0.6%]) among guselkumabrandomized patients. No patient developed an opportunistic infection or died. Conclusion. In biologic-naive PsA patients, guselkumab provided sustained improvements across diverse manifestations and maintained a favorable risk-benefit profile through week 52.

Guselkumab, an inhibitor of the IL-23p19 subunit, provides sustained improvement in signs and symptoms of active psoriatic arthritis: 1 year results of a phase III randomised study of patients who were biologic-naïve or TNFα inhibitor-experienced

“…23 Guselkumab 100 mg Q4W and Q8W have been shown to effectively treat such manifestations, 15 with maintenance of dactylitis and enthesitis resolution rates through 1 year. 19 Nearly a third of DISCOVER-1 participants previously received one or two TNFis, permitting guselkumab efficacy and safety evaluations across TNFi-exposure cohorts. At baseline, the smaller TNFi-experienced cohort was characterised by longer-standing and more active joint disease, higher levels of systemic inflammation, greater functional impairment, and more patients with extensive skin involvement and methotrexate use, than TNF-naïve patients.…”

“…While DISCOVER-1 did not evaluate radiographic progression, guselkumab 100 mg Q4W significantly inhibited structural damage progression at Week24 of DISCOVER-2, 15 and low, comparable levels of progression were seen with 1 year of guselkumab 100 mg Q4W or Q8W in that study. 19 Results of DISCOVER-1 are limited by the 1-year study period, a relatively short time frame for assessing patient retention, maintenance of effect and tolerability in a chronic lifelong disorder. Conclusions drawn are also limited by the lack of placebo control beyond Week24.…”

“… 23 Guselkumab 100 mg Q4W and Q8W have been shown to effectively treat such manifestations, 15 with maintenance of dactylitis and enthesitis resolution rates through 1 year. 19 …”

“…Clinical efficacy, safety and patient retention through 1 year of DISCOVER-1 are consistent with 1-year findings from the larger DISCOVER-2 trial of 739 biologic-naïve patients with PsA, in which significant improvements in arthritis symptoms, skin disease, dactylitis and enthesitis (pooled across studies), physical function, and physical aspects of HRQoL seen at Week24 were maintained by both guselkumab 100 mg Q4W and Q8W, and 94% of guselkumab-randomised patients also completed study agent, through 1 year. 19 The DISCOVER trials are the first to document retention of patients with PsA receiving an IL-23p19 inhibitor through 1 year. While DISCOVER-1 did not evaluate radiographic progression, guselkumab 100 mg Q4W significantly inhibited structural damage progression at Week24 of DISCOVER-2, 15 and low, comparable levels of progression were seen with 1 year of guselkumab 100 mg Q4W or Q8W in that study.…”

“…These determinations assumed a constant incidence over time, a customary approach to standardise AE data for comparative purposes. Numbers of patients requiring treatment for an additional AE (number needed to harm (NNH)), were determined for these AE categories as previously detailed, 19 with the intent of reporting only positive values, that is, those suggesting excess risk with guselkumab over placebo.…”