Guselkumab Demonstrates Favorable Benefit-Risk Profile in Biologic-Naive Patients With Active Psoriatic Arthritis

Guselkumab demonstrates a favorable benefit-risk profile in patients with active psoriatic arthritis (PsA) who are both biologic-naive or had previously received tumor necrosis factor inhibitor (TNFi) α treatment, according to findings from 2 studies published in The Lancet.

In the DISCOVER-1 study, the researchers sought to assess guselkumab in biologic-naive patients with active PsA, including treatment with TNFis; the DISCOVER-2 study was to evaluate guselkumab in biologic-naive patients with active PsA.

Both the DISCOVER-1 and DISCOVER-2 trials (ClinicalTrials.gov Identifiers: NCT03162796 and NCT03158285, respectively) were multicenter, double-blind, randomized, controlled, 3-arm phase 3 trials. DISCOVER-1 included patients with active PsA despite treatment with standard therapies, including nonbiologic disease-modifying antirheumatic drugs (DMARDs), apremilast, and nonsteroidal anti-inflammatory drugs (NSAIDs) and those who may have previously received treatment with 1 or 2 TNFis; DISCOVER-2 included biologic-naive patients with active PsA despite treatment with standard therapies.

Eligibility requirements were similar across both trials: DISCOVER-1 enrolled patients with active PsA (≥3 swollen and tender joints) and a C-reactive protein (CRP) ≥0.3 mg/dL. Eligible patients with PsA had inadequate response or intolerance to standard therapies, including ≥4 months of apremilast, ≥3 months of nonbiologic DMARDs, or ≥4 weeks of NSAIDs. Patients included in this study could continue to receive background use of stable doses of 1 nonbiologic DMARD, oral corticosteroids, and NSAIDs or other analgesics. In DISCOVER-2, the researchers included patients with PsA for ≥6 months, who had ≥5 tender and swollen joints and CRP levels ≥0.6 mg/dL, and either an inadequate response or intolerance to the standard therapies.

For both the DISCOVER-1 and DISCOVER-2 trials, patients were randomly assigned to receive subcutaneous injections of guselkumab 100 mg every 4 weeks, guselkumab 100 mg at weeks 0, 4, then every 8 weeks, or placebo. The primary end point for both trials was 20% improvement according to the American College of Rheumatology response criteria (ACR20) at week 24.

Specifically, the DISCOVER-1 included 381 patients who were randomly assigned to receive guselkumab every 4 weeks (n=128), every 8 weeks (n=127), or placebo (n=126). A total of 362 patients continued to receive treatment up to week 24. Compared with the placebo group, patients in the week 4 and 8 groups achieved ACR20 at week 24 in significantly greater percentages (22% [95% CI, 15%-30%] vs 59% [95% CI, 50-68] and 52% [95% CI, 43%-61%], respectively), with percentage differences vs placebo of 37% (95% CI, 26%-48%) and 30% (95% CI, 19%-41%), respectively (both P <.0001). No serious adverse events (AEs) were reported among patients in the 4-week group vs the 8-week (3%) and placebo group (4%) up to week 24Of note, no death or serious infections were observed among patients who received guselkumab in the study.

The DISCOVER-2 trial included 741 patients who were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). A total of 716 continued to receive treatment up to week 24. Compared with the placebo group, a significantly greater percentage of patients in the 4- and 8-week groups achieved ACR20 response up to week 24 (33% [95% CI, 27%-39%] vs 64% [95% CI, 57%-70%] and 64% [95% CI, 58%-70%], with percentage differences vs placebo of 31% (95% CI, 22%-39%) and 31% (95% CI, 23%-40%), respectively (both P <.0001). Among patients receiving guselkumab every 4 and 8 weeks vs placebo, 3% and 1% vs 3%, respectively experienced AEs; however, no deaths occurred across any groups.

Study limitations included the relatively short duration of treatment, the fact that the enrollment of patients in the DISCOVER-1 and -2 trials with CRPs ≥0.3 mg/dL and ≥0.6 mg/dL, respectively, may affect the generalizability of results. In addition, the DISCOVER-2 study noted relatively high placebo response rates for both joint and skin disease outcomes; however, the researchers indicated that these placebo response rates were consistent with similar findings in biologic-naive patients with PsA, most likely reflecting patients’ higher expectations of efficacy from other available potent biologic therapies.

Overall, the researchers concluded that guselkumab, which specifically inhibits interleukin-23, demonstrated a favorable benefit-risk profile and may be effective in the treatment of biologic-naive patients with active PsA who may be receiving TNFi treatment and those with active PsA.

References

1. Deodhar A, Helliwell PS, Boehncke WH, et al. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): A double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395:1115-1125.

2. Mease PJ, Rahman P, Gottlieb AB, et al. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): A double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395:1126-1136.