Guselkumab Safety in Psoriatic Arthritis Consistent Regardless of Prior TNF Inhibitor Exposure

Proton Rahman, MD

Leveraging data from 4 clinical trials with more than 1500 patients receiving guselkumab offers rheumatologists and other providers with new insight into the effectiveness of the agent for treatment of psoriatic arthritis (PsA) based on whether or not a patient has prior exposure to tumor necrosis factor-α (TNF) inhibitors.¹

Using data from the DISCOVER-1,DISCOVER-2, COSMOS, and the phase 2 study of guselkumab, results of the pooled analysis suggest the safety of guselkumab, which remained favorable for up to 2 years, was consistent in patients with psoriatic arthritis with prior exposure to TNF inhibitor therapy and TNF-naïve patients.

“These results demonstrate that guselkumab was well tolerated in studies continuing for 1 to 2 years among patients with moderate-to-severe PsA regardless of TNFi experience and concomitant [methotrexate] use, making the findings relevant to the PsA population in a clinical setting,” wrote investigators. Together with the robust efficacy data, these results further support the long-term use of guselkumab as an initial biologic therapy or in those who have failed or were intolerant to TNFi treatment.”

With TNF inhibitors serving as a first-line therapy for many with PsA, a large percentage of patients with PsA have exposure to TNF inhibitor therapy before switching to biologic therapies, such as the IL-23 inhibitor guselkumab. With this in mind, a team of investigators led by sought to explore the safety of guselkumab based on prior exposure to TNF inhibitor and methotrexate use by performing pooled analyses using data from phase 2 and phase 3 studies.

To do so, investigators pooled data from the phase 2 study of guselkumab as well as the DISCOVER-1, DISCOVER-2, and COSMOS studies. From these studies, patients obtained data related to 1554 randomized patients, with 373, 664, and 517 randomized to guselkumab every 4 weeks, guselkumab every 8 weeks, and placebo therapy. The primary outcome of interest for the analyses was the time-adjusted adverse event rates, which was expressed as events per 100 patient-years. Investigators pointed out clinical laboratory findings were also assessed during the placebo-controlled period and through end of study.

Upon analysis, results indicated the adverse rates among those without prior exposure through week 24 were 220.8 per 100 person-years compared to 251.6 per 100 person-years among those with prior exposure to TNF inhibitor therapy among those in the combined guselkumab group. Among those receiving placebo, the adverse event rate in analyses comparing pooled populations of guselkumab recipients against placebo recipients, results indicated the guselkumab group had an adverse event rate of 196.1 per 100 person-years among those without prior exposure to TNF inhibitors and 303.0 per 100 person-years in those with prior exposure to TNF inhibitors.

In long-term evaluations, results suggested the low adverse event rates observed through 24 weeks were maintained among guselkumab-treated patients, with rates of 136.69 and 174.0 per 100 person-years, respectively, among those without TNF inhibitor exposure and those with TNF inhibitor exposure. Investigators also pointed out rates of adverse events leading to discontinuation, serious adverse events, and other adverse events of interests were consistent between placebo and guselkumab-treated patients through week 24 treatment regardless of prior TNF inhibitor use and remained low through the end of the studies.

Investigators pointed out multiple limitations within their study for clinicians to consider when interpreting findings. Among these was a lack of comparator after the first 24 weeks and the trials not being powered for rare events. Investigators also pointed out DISCOVER-2 was the only study to follow patients with PsA for 2 years, with the other 3 trials included limited to just 1 year of follow-up.

1. Rahman P, Boehncke W-H, Mease PJ, et al. Safety of guselkumab with and without prior TNF-α inhibitor treatment: Pooled results across four studies in patients with psoriatic arthritis. The Journal of Rheumatology. 2023. doi:10.3899/jrheum.220928