Pooled Safety Results Through One Year of Two Phase-3 Trials of Guselkumab in Patients with Psoriatic Arthritis.

OBJECTIVE: Evaluate safety of guselkumab (monoclonal antibody targeting IL-23p19) in psoriatic arthritis (PsA) patients through 1year (1Y) of the Phase-3 DISCOVER-1&2 trials. METHODS: Patients with active PsA (N=1120; biologic-naïve except the118 TNFi-treated DISCOVER-1 patients) were randomized to subcutaneous guselkumab 100 mg every 4 weeks (Q4W) or at Week 0, Week4, then Q8W; or placebo. At Week24, placebo patients switched to guselkumab 100 mg Q4W. Treatment continued through 1Y and 2Y for DISCOVER-1&2, respectively. In this pooled analysis, patients with ≥1 adverse event (AE) through 1Y were standardized for 100 patient-years of follow-up [100PY]). RESULTS: Through Week24, AEs were consistent between placebo- and guselkumab (Q4W+Q8W)-treated patients: AEs 143/100PY and 151/100PY; serious AEs 7.1/100PY and 4.4/100PY; AEs leading to study agent discontinuation 4.1/100PY and 3.8/100PY, respectively. Through 1Y, no active tuberculosis, opportunistic infections, or inflammatory bowel disease, and low rates of malignancy and major adverse cardiovascular events, were observed in guselkumab-treated patients. Injection-site reactions occurred in 1-2%, and antibodies to guselkumab in 4.5% of guselkumab-treated patients through 1Y; the vast majority of antibodies to guselkumab were non-neutralizing. Serum hepatic transaminase elevations (more common with Q4W than Q8W) and decreased neutrophil counts were generally mild, transient, and did not require treatment discontinuation, with minimal change from Week24 to 1Y. CONCLUSION: Guselkumab 100 mg Q4W and Q8W were well tolerated in PsA patients, with no new safety concerns through 1Y of the Phase-3 DISCOVER trials. Guselkumab safety through 1Y in PsA patients is consistent with that established in guselkumab-treated psoriasis patients