Safety of Guselkumab With and Without Prior Tumor Necrosis Factor Inhibitor Treatment: Pooled Results Across 4 Studies in Patients With Psoriatic Arthritis.
Rahman P., Boehncke W-H., Mease PJ., Gottlieb AB., McInnes IB., Shawi M., Wang Y., Sheng S., Kollmeier AP., Theander E., Yu J., Leibowitz E., Marrache AM., Coates LC.
OBJECTIVE: Assess pooled safety results through the end of the phase II/III studies of guselkumab (GUS; ≤ 2 years) in tumor necrosis factor inhibitor (TNFi)-naïve and -experienced patients with psoriatic arthritis (PsA). METHODS: Data were pooled from the Phase 2 and DISCOVER-1 (both TNFi-naïve and -experienced), DISCOVER-2 (TNFi-naïve), and COSMOS (TNFi-experienced) studies. Patients with active PsA were randomized to GUS 100 mg every 4 or 8 weeks (Q4W + Q8W = Combined GUS) or placebo (PBO) with crossover to GUS Q4W or Q8W at week 24. Time-adjusted adverse event (AE) rates (events/100 patient-years [PY]) and clinical laboratory findings were assessed during the PBO-controlled period and through end of study (≤ 2 years). RESULTS: Of 1554 randomized patients (n = 373 [GUS Q4W], 664 [GUS Q8W], and 517 [PBO]), 1138 (73.23%) were TNFi-naïve and 416 (26.77%) were TNFi-experienced. Respective AE rates through week 24 were 220.8/100 PY (TNFi-naïve) and 251.6/100 PY (TNFi-experienced) in the Combined GUS group and 196.1/100 PY (TNFi-naïve) and 303.0/100 PY (TNFi-experienced) in the PBO group. Among all GUS-treated patients (including those who crossed over from PBO), low AE rates were maintained during long-term evaluation in both TNFi-naïve (139.7/100 PY) and TNFi-experienced (174.0/100 PY) patients. Rates/100 PY of AEs leading to treatment discontinuation, serious AEs, and other AEs of interest, as well as occurrence of elevated hepatic transaminase levels and decreased neutrophil counts were consistent between PBO and GUS-treated patients through week 24 regardless of prior TNFi use and remained low through the end of the studies. CONCLUSION: The safety profile of GUS in TNFi-experienced patients was consistent with that in TNFi-naïve patients, which remained favorable for up to 2 years. [ClinicalTrials.gov: Phase 2 (NCT02319759), DISCOVER-1 (NCT03162796), DISCOVER-2 (NCT03158285), and COSMOS (NCT03796858)].