Guselkumab Safety Similar to Placebo for Psoriasis Patients Over 5 Years

Mark Lebwohl, MD

Interleukin-23 (IL-23) inhibitor guselkumab provided consistent long-term safety in patients being treated for psoriasis across an entire clinical program, according to new pooled analysis.

In new collected data from 7 clinical trials assessing the Janssen monoclonal antibody, a team of investigators observed approximately 5 severe adverse events (AEs) per 100 patient-years of follow-up among those who were treated with guselkumab.

The investigation team, led by Mark Lebwohl, MD, of the Icahn School of Medicine at Mount Sinai, noted the rate of AEs overall were similar across guselkumab and placebo treatment across in data pooled from 1 phase 2 trial and 6 phase 3 trials for the drug.

Investigators sought to assess the cumulative safety experience of patients with psoriasis receiving treatment in any of the 7 selected guselkumab clinical trials, including:

• X-PLORE
• VOYAGE 1 and 2
• NAVIGATE
• ORION
• ECLIPSE
• A Japan registration trial

The team used 16-week, placebo-controlled safety outcome data from all but the ECLIPSE trial, accumulating 1220 patients treated with guselkumab versus 544 patients receiving placebo. The total assessment pool included 2891 patients receiving guselkumab through the end of the reported for each trial—including those who were initially randomized to either placebo or adalimumab at baseline of their trial.

Lebewohl and colleagues sought exposure-rated rates of Ads per 100 patient-years of follow-up through ≤5 years of treatment with either guselkumab or placebo.

Excluding the Japan registration trial—in which patients had lower mean weight, body mass index (BMI), and greater measures of disease severity per body surface area (BSA) and Psoriasis Area and Severity Index (PASI) scores—patients reported fairly consistent baseline demographics and clinical characteristics across each trial.

Mean patient age was approximately 45 years old; a majority of patients were male and caucasian.

In the assessment of placebo-controlled treatment periods including 1220 guselkumab patients with 378 patient years total, investigators observed similar AE rates per 100 patient-years among guselkumab (346) and placebo patients (341). Serious AE rates for each arm were 6.34 and 6.66 per 100 person-years, respectively.

Investigators additionally reported similar infection rates across treatment and placebo arms; patients administered guselkumab did report a 0.26 per 100 patient-year rate for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events—versus none among the placebo arm.

Among the combined 2891 guselkumab patients through the end of the reporting period of the 7 trials, mean AE rates were 169 per 100 patient-years (95% CI, 166 - 172), 5.26 serious AEs per 100 patient-years (95% CI, 4.79 - 5.77), and 65.92 infections per 100 patient-years (95% CI, 64.22 - 67.65).

“Through the end of the reporting period, rates of events remained low for guselkumab-treated patients,” investigators wrote.

The team concluded these findings elucidated a favorable safety profile for the IL-23 across 5 years of treatment among adults with psoriasis.

The study, “Safety of Guselkumab in Patients with Moderate-to-Severe Psoriasis: Pooled Analyses Across Clinical Studies,” was presented at Fall Clinical Dermatology 2022.