An analysis of 11 late-stage clinical trials shows guselkumab provides a consistent and comparable safety profile to placebo in treated patients.
Long-term use of guselkumab (TREMFYA) for the treatment of psoriasis and/or psoriatic arthritis (PsA) was associated with consistent safety comparable to placebo outcomes in previous clinical trials, according to a new analysis.
In an extensive assessment of previously published clinical trial safety data for the biologic therapy, investigators reported minimal to no instances of gastric disease development nor treatment-related infections among 2000-plus treated patients. The findings, presented at the Congress of Clinical Rheumatology (CCR) East 2023 Annual Meeting in Destin, FL, this week, provide what investigators believe is the most comprehensive analysis of guselkumab safety outcomes to date.
Led by Bruce Strober, MD, PhD, clinical professor of dermatology at Yale University School of Medicine and dermatologist with Central Connecticut Dermatology Research, investigators sought to pool available phase 2 and 3 study data to provide an extensive profile of guselkumab’s safety in use of treating psoriatic disease. An interleukin-23 (IL-23) inhibitor, guselkumab has been supported by late-stage data showing its benefit and safety in patients with moderate to severe psoriasis and with active PsA, Strober and colleagues noted.
Their integrated analysis included safety data from 11 trials—4 of which pertained to PsA (phase 2; DISCOVER-1; DISCOVER-2; COSMOS) and 7 of which pertained to psoriasis (X-PLORE; VOYAGE 1 and 2; NAGIVATE; ORION; ECLIPSE; and Japanese registration study).
In the psoriasis studies, guselkumab was commonly administered as a 100 mg subcutaneous injection at baseline, week 4, then every 8 weeks. In all but 2 psoriasis studies, patients initiated on placebo were crossed over to guselkumab every 8 weeks after week 16. In the PsA studies, placebo patients were crossed over to guselkumab every 4 or 8 weeks at week 24.
Investigators used summarized safety data from the placebo-controlled portion of the observed trials, as well as through the end of reporting periods up to 5 years in psoriasis patients and up to 2 years in PsA patients. They sought incident rates of key safety events, with adjustments for follow-up duration and events per 100 patient-years.
In total, Strober and colleagues observed 10,787 patient-years of follow-up of guselkumab—8662 from patients with psoriasis and 2125 from patients with PsA. Total patients treated with guselkumab was 4399—2891 with psoriasis and 1508 with PsA.
The team observed 281 (95% CI, 269 – 292) adverse events per 100 patient-years among patients treated with guselkumab, versus 272 (95% CI, 256 – 289) among patients on placebo during the placebo-controlled period. There were fewer serious adverse events among guselkumab-treated patients (5.6; 95% CI, 4.1 – 7.4) than placebo-treated patients (7.8; 95% CI, 5.3 – 11.2).
Rates of serious infections (1.0; 95% CI, 0.5 – 2.0), malignancy (0.59; 95% CI, 0.19 – 1.37) and major adverse cardiovascular events (0.35; 95% CI, 0.07 – 1.02) among guselkumab-treated patients per 100 patient-years were similar if not lower than placebo-treated patient rates.
In the pooled patient data through trial reporting periods, investigators observed just 1.8 (95% CI, 1.6 – 2.1) adverse events leading to treatment discontinuation per 100 patients-years among guselkumab-treated patients.
“The rates of safety events evaluated remained consistent through the end of the reporting period for guselkumab-treated patients,” investigators wrote. “No cases of Crohn’s disease or ulcerative colitis were reported in guselkumab-treated patients. No serum sickness-like or anaphylactic reactions related to guselkumab were reported. No opportunistic infections were reported in any guselkumab-treated patients with psoriasis.”
The team concluded that their comprehensive analysis of available late-stage guselkumab safety data showed the biologic was favorably and consistently safe—even when compared to previous relevant reports.
“Safety event rates in guselkumab-treated patients were similar to those observed with placebo and remained stable throughout the long-term follow-up,” they wrote.