Guselkumab’s safety profile consistent regardless of TNF-inhibitor use in psoriatic arthritis
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The 2-year safety profile of guselkumab appears consistently favorable across patients with psoriatic arthritis who are either naïve or experienced with TNF inhibitors, according to data published by The Journal of Rheumatology.
“Guselkumab, a monoclonal antibody that selectively inhibits interleukin (IL)-23 p19, was the first agent in its class approved for patients with active PsA,” Proton Rahman, MD, FRCPC, of the Craig L. Dobbin Genetics Research Center at Memorial University of Newfoundland, in Canada, and colleagues wrote. “The majority of these patients were TNFi-naïve, while approximately one-quarter were TNFi-experienced.”
To examine 2-year safety outcomes among patients with PsA receiving guselkumab (Tremfya, Janssen), either with or without TNF-inhibitor treatment, Rahman and colleagues conducted a pooled analysis of data from a phase 2 study, as well as three phase 2 studies — DISCOVER-1, DISCOVER-2 and COSMOS. The phase 2 and DISCOVER-1 studies included both patients with and without TNF-inhibitor use, while DISCOVER-2 featured those who were TNF-inhibitor naïve only, and COSMOS enrolled only those who had used TNF inhibitors but demonstrated an inadequate response.
Eligible patients in DISCOVER-1 and -2 were randomized to receive guselkumab 100 mg every 4 or 8 weeks or placebo, while those in the phase 2 and COSMOS studies received either guselkumab or placebo every 8 weeks. In all studies, participants in the placebo arms crossed over to guselkumab at week 24. In addition concomitant methotrexate and corticosteroid use accepted were accepted in all trials. Patients in DISCOVER-1 were followed for 2 years, while those in the other studies were followed for 1 year.
Throughout all included studies, researchers monitored patients for adverse events leading to discontinuation and serious adverse events. Adverse events of particular interest included serious and opportunistic infections, serious adverse events impacting the gastrointestinal system, malignancies, and cardiovascular death and related events. Events were categorized depending on treatment received and the number of doses.
The pooled data included a total of 1,554 patients. Among these patients, 1,138 were TNF-inhibitor naïve, while 416 were TNF-inhibitor experienced. Meanwhile, 373 of the included patients received guselkumab every 4 weeks, 664 received the therapy every 8 weeks and 517 patients received placebo therapy for the first 16 weeks.
According to the researchers, adverse event rates through week 24 for the combined guselkumab group were 220.8 per 100 patient-years for the TNF-inhibitor naïve, and 251.6 per 100 patient-years among the experienced. In the placebo group, rates were 196.1 and 303 per 100 patient-years, respectively.
Low rates of adverse events were maintained long-term among all patients who received guselkumab, including those who crossed over from placebo, with rates of 139.69 events per 100 patient-years among the TNF inhibitor-naïve, and 174 events per 100 patient-years among the experienced.
Rates of serious adverse events, events resulting in discontinuation, and other adverse events of interest were consistent across treatment arms regardless of TNF-inhibitor use and remained low throughout all studies, according to the researchers.
“Integrated analyses across four phase 2/3 studies of PsA patients demonstrated that the safety profile of guselkumab remained consistent, regardless of prior TNFi or concomitant [methotrexate] use,” Rahman and colleagues wrote. “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.”
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