Guselkumab Safety Remains Consistent in Psoriasis, Psoriatic Arthritis

Proton Rahman, MD

Guselkumab (Tremfya) provides a similar safety profile in patients taking the biologic therapy for either psoriatic arthritis or psoriasis, according to new assessment of phase 3 findings.

In new data presented at the American College of Rheumatology (ACR) 2021 Convergence this week, a team of Janssen-funded investigators observed the company’s interleukin-23 (IL-23) pathway inhibitor was associated with consistent safety outcomes in patients with either psoriatic disease up to 1 year in a pair of pivotal trial programs: DISCOVER 1 and 2 for psoriatic arthritis, and VOYAGE 1 and 2 for psoriasis.

The US Food and Drug Administration (FDA) approved guselkumab for active psoriatic arthritis in July 2020 on the basis of DISCOVER findings. It was the first treatment indicated for patients that targeted the IL-23 pathway. Guselkumab was previously approved for patients with plaque psoriasis in July 2017, on the basis of VOYAGE trial data.

Proton Rahman, MD, a rheumatologist and University Research Professor at Memorial University of Newfoundland, sought to compare clinical safety outcome data of guselkumab in patients with psoriatic arthritis and psoriasis. For this, they observed DISCOVER 1 and 2, and VOYAGE 1 and 2, respectively.

The DISCOVER Trial Program

The DISCOVER trials included 1120 patients who had active psoriatic arthritis despite receiving standard therapy. A majority of guselkumab-treated patients were naïve to biologic therapy, and approximately 30% of patients in DISCOVER 1 had previous exposure to either 1 or 2 tumor necrosis factor (TNF) inhibitor therapies. Concomitant methotrexate, oral corticosteroid, and non-steroidal anti-inflammatory drugs (NSAIDs) were permitted in the trial program, and used by 57%, 17%, and 64% of patients, respectively.

Investigators randomized patients to 3 treatment arms:

• Subcutaneous guselkumab 100 mg at baseline, week 4, then every 8 weeks
• Subcutaneous guselkumab 100 mg every 4 weeks
• Placebo, then switched to subcutaneous guselkumab 100 mg every 4 weeks at week 24

The VOYAGE Trial Program

VOYAGE 1 and 2 assessed similar regimens of subcutaneous guselkumab in patients with moderate to severe psoriasis, yet differed in eligible concomitant treatment criteria; patients were not permitted to use methotrexate during the assessment.

The program included 1245 patients randomized to either guselkumab at baseline, week 4 and 12, then once every 8 weeks, or placebo at baseline, week 4 and 12, then crossover to guselkumab at weeks 16 and 20, then once every 8 weeks.

Safety Findings

Rahman and colleagues summarized adverse events and laboratory parameters—per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE)—through the trial programs’ placebo-controlled periods and through 1 year of follow-up.

They observed “generally consistent” guselkumab safety profiles in patients with either psoriasis or psoriatic arthritis, with similarities in patients’ time-adjusted incidence rates for total adverse events and serious adverse events, serious infections, malignancies, major adverse cardiovascular events, and adverse event-driven treatment discontinuation. They observed no cases of anaphylaxis nor opportunistic infections in treated patients.

Decreased neutrophil counts and rates of elevated hepatic trasnaminases were more frequently in treated patients with psoriatic arthritis versus those with psoriasis. However, investigators noted these cases were mostly an NCI-CTCAE Grade 1 or 2—indicating a generally transient profile, requiring no medical intervention, resolving spontaneously, and not leading to interrupted nor discontinued therapy.

The proportion of patients with elevated aspartate transaminase/alanine aminotransferase (AST/ALT) was greater in the DISCOVER trial participants who received guselkumab every 4 weeks and those who reported baseline methotrexate use, versus those received treatment every 8 weeks and those who did not take methotrexate.

Nonetheless, Rahman and colleagues concluded the safety profile of guselkumab in patients with psoriasis or psoriatic arthritis was consistent, and associated with similar outcomes.

The study, “Comparable Safety Profile of Guselkumab in Psoriatic Arthritis and Psoriasis: Results from Phase 3 Trials Through 1 Year,” was presented at ACR 2021.