Guselkumab safe, well tolerated in patients with psoriatic arthritis

Treatment with the monoclonal antibody targeting interleukin [IL]-23p19 guselkumab 100 mg, given either every 4 (Q4W) or 8 weeks (Q8W), is well tolerated in patients with psoriatic arthritis (PsA), with no new safety concerns through 1 year, according to pooled results of the DISCOVER-1 and DISCOVER-2 phase III trials.

“Furthermore, the guselkumab safety profile in patients with PsA through 1 year is consistent with that in patients with psoriasis who received up to 5 years of guselkumab,” the researchers said.

A total of 1,120 patients with active PsA (biologic-naïve except for 118 patients treated with tumour necrosis factor [TNF] inhibitors in DISCOVER-1) were randomly assigned to receive subcutaneous guselkumab 100 mg Q4W or at week 0, week 4, then Q8W, or placebo. At week 24, patients receiving placebo switched to guselkumab 100 mg Q4W.

Treatment continued through 1 year for DISCOVER-1 and 2 years for DISCOVER-2. In pooled analysis, patients with one or more adverse events (AEs) through 1 year were standardized for 100 patient-years (PYs) of follow-up.

AEs were consistent between patients treated with guselkumab and those with placebo through week 24: the rates of AEs were 142.8 and 150.6 per 100 PYs, serious AEs were 7.1 and 4.4 per 100 PYs, and AEs leading to treatment discontinuation were 4.1 and 3.8 per 100 PYs, respectively. [J Rheumatol 2021;48:1815-1823]

In patients treated with guselkumab, no uveitis, active tuberculosis, inflammatory bowel disease, or opportunistic infections were noted, while rates of malignancy and major adverse cardiovascular events were low through 1 year.

Injection-site reactions occurred in 1.7 percent and antibodies to guselkumab in 4.5 percent of patients treated with guselkumab through 1 year. Most of these antibodies, however, were non-neutralizing.

In addition, serum hepatic transaminase elevations (more common with Q4W than Q8W dosing) and lower neutrophil counts were mostly mild, transient, and did not lead to treatment discontinuation, with minimal change from week 24 through 1 year.

These findings support those previously reported for each trial through week 24 and through 1 year, as well as the long-term safety results through 4 years of guselkumab treatment in the VOYAGE-1 and VOYAGE-2 trials involving patients with moderate-to-severe psoriasis. [Lancet 2020;395:1115-1125; Lancet 2020;395:1126-1136; Arthritis Rheumatol 2021;73:604-616; J Dermatolog Treat 2020;13:1-9]

“Biologics have provided a highly effective alternative for treating the signs and symptoms of PsA and psoriasis, including anti-TNF agents and monoclonal antibodies targeting IL-12/23, IL-17, and IL-23,” the researchers said.

“The safety profiles of anti-TNF agents and ustekinumab, a monoclonal antibody targeting IL-12/23, are well established, with IL-17 antibodies accruing longer-term data more recently,” they added. [Immunopharmacol Immunotoxicol 2012;34:548-560; Drug Saf 2019;42:751-768]

The current study was limited by its short follow-up time, but the upcoming 2-year results from DISCOVER-2 will provide longer-term safety results. Additionally, the trials were not powered to detect rare events, according to the researchers.