Guselkumab efficacious for joint, skin symptoms, physical function in PsA
ATLANTA — Guselkumab, administered either every 4 or 8 weeks, is efficacious for joint and skin symptoms, as well as physical function and quality of life, among patients with active psoriatic arthritis who are biologic-naive or previously received TNF inhibitors, according to data presented at ACR/ARP 2019.
“Psoriatic arthritis does not have as many treatment options as rheumatoid arthritis does,” Atul Deodhar, MD, of Oregon Health & Science University, in Portland, told Healio Rheumatology. “The IL-23/IL-17 axis has been found to be extraordinarily important in the pathogenesis of spondyloarthritis in general, and the expedience of this drug in skin psoriasis was dramatic. So, IL-23 inhibitors probably are the strongest drugs currently that are available to treat skin psoriasis.”
“There is a head-to-head study of guselkumab vs. secukinumab published in The Lancet, where this drug was found to be superior to even secukinumab, which is an IL-17 inhibitor, which is better than TNF inhibitors when it comes to the skin,” he added. “It was important to see what the effects of this drug on the joints are, because 30% of patients with skin psoriasis have psoriatic arthritis also.”
To analyze the efficacy and safety of guselkumab (Tremfya, Janssen), an IL-23p19 monoclonal antibody, among patients with active PsA who were biologic-naive or had been treated with a prior TNF inhibitor, Deodhar and colleagues conducted the phase 3 DISCOVER-1 trial. A total of 381 adult patients were included in the analysis, in which they were randomly stratified — based on baseline DMARD and prior TNF inhibitor use — to receive either 100 mg of guselkumab every 4 weeks, 100 mg of guselkumab every 8 weeks or placebo. Stable use of certain nonbiologic DMARDs, oral corticosteroids and NSAIDs were allowed at this time.
At week 16, participants with a less than 5% improvement in tender and swollen joint counts could start or increase doses of allowed medications while continuing their assigned study regimen. The primary endpoint was ACR20 criteria at week 24.
Major secondary endpoints included Investigator’s Global Assessment (IGA) psoriasis response at week 24, in patients with a 3% or greater affected body surface area and an IGA grade of 2 or more at baseline; changes in DAS28-CRP, health assessment questionnaire disability index (HAQ-DI) and the Short Form 36 (SF-36) physical component summary (PCS) scores, as well as ACR50/70 response at week 24; and ACR20/50 response at week 16. Adverse events were reported through week 24.
The researchers prespecified two multiplicity control procedures — global and U.S — due to regional health authority differences in regulatory requirements for multiplicity control. Deodhar presented the results of statistical testing through the U.S. procedures.
“We had previously done a phase 2 study, and in general, in rheumatology, phase 2 study results are sometimes exaggerated compared to phase 3,” Deodhar said. “The phase 2 results were very good with guselkumab. Also, the phase 2 studies are smaller, while the phase 3 studies are much larger. The question was whether the phase 3 study results would look the same.”
According to the researchers, 58.6% of patients treated with guselkumab every 4 weeks, and 52.8% treated every 8 weeks, achieved the ACR20 response at week 24, compared with 22.2% of those in the placebo group (P < .001). Response rates were consistent among the subgroups of participants with or without prior TNF inhibitor use.
In addition, patients in both guselkumab groups demonstrated significantly greater improvement in HAQ-DI and SF-36 PCS scores, compared with the placebo group, from baseline to week 24.
Among the 249 participants with 3% or greater effected body surface area and an IGA grade of 2 or more at baseline, significantly more individuals treated with guselkumab achieved IGA response compared with those who received placebo.
The researchers reported nine cases of serious adverse events, two serious infections and one death.
“The results were equally good, if not better than the phase 2 study,” Deodhar said. “It showed very good results on the skin, which was expected, but the joint results were equally good, or even better.”
“The other thing is that this was an extraordinarily safe drug,” he added. “The infections were equal in the active drug and placebo groups, and the same thing has been found in the psoriasis program. The infection risk is surprisingly low. Overall these are very positive results. The DISCOVER-2 trial will tell us about the structural outcomes, which will be presented later this week.” – by Jason Laday
Deodhar A. Guselkumab, an anti-interleukin-23p19 monoclonal antibody, in patients with active psoriatic arthritis who were biologic-naive or prior TNF inhibitor-treated: Week 24 results of a phase 3, randomized, double-blind, placebo-controlled study. Presented at: American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; Nov. 9-13, 2019; Atlanta.
Disclosure: Deodhar reports professional relationships with AbbVie, Amgen, Boehringer Ingelheim, BMS, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB Pharma.