In patients with active psoriatic arthritis, who are biologic-naïve, guselkumab (Tremfya, Janssen) improved joint and skin symptoms, physical function, and quality of life, and resolved enthesitis and dactylitis, according to a study presented at annual meeting of the American College of Rheumatology in Atlanta on November 12.
Guselkumab, an anti-interleukin-23p19 monoclonal antibody, is approved for the treatment of psoriasis. Researchers assessed guselkumab efficacy and safety in two phase 3 trials in psoriatic arthritis, DISCOVER-1, which was included in the Plenary Session on November 10, and DISCOVER-2, presented here.
In an interview with Rheumatology Network, Philip J. Mease, M.D., of the Swedish Medical Center and University of Washington in Seattle, Washington, said that “this large phase 3 registry trial (for purpose of regulatory approval) confirms the ability of this agent to effectively treat numerous clinical domains of psoriatic arthritis including arthritis, enthesitis, dactylitis, as well as skin and nail disease, improve function and quality of life, and inhibit structural damage progression as measured by x-ray.”
DISCOVER-2 included 739 biologic-naïve patients with moderate-to-severe disease (mean swollen/tender joints: 12/21, median CRP: 1.2 mg/dL, mean body surface area [BSA] with psoriasis: 17.4 percent, Investigator’s Global Assessment [IGA]=3 or 4: 46.1 percent of patients) despite non-biologic disease-modifying antirheumatic drugs (DMARDs) and/or nonsteroidal anti-inflammatory drugs (NSAIDs). Participants were randomized to guselkumab 100mg every four weeks (n=245), guselkumab 100mg every eight weeks (n=248), or placebo (n=246). Concomitant stable select non-biologic DMARDs, oral corticosteroids, and NSAIDs were allowed. At week 16, patients with less than 5 percent improvement in tender and swollen joints could initiate/increase the dose of permitted medications.
The primary endpoint was ACR20 response at week 24, and major secondary endpoints at week 24 were IGA psoriasis response (IGA=0/1 and ≥2-grade reduction) in patients with 3 percent or greater BSA psoriasis and IGA 2 or more at baseline; changes in Health Assessment Questionnaire without Disability Index (HAQ-DI), psoriatic arthritis-modified van der Heijde-Sharp (vdH-S), and SF-36 physical component score (PCS)/mental component score (MCS) scores; resolution of enthesitis/dactylitis (using pooled DISCOVER-1 and 2 data); change in DAS28-CRP; and ACR50/70 responses.
Results showed that 63.7 percent of patients assigned to guselkumab every four weeks and 64.1 percent of patients assigned to the drug every eight weeks achieved ACR20 response at week 24 versus 32.9 percent of the placebo group (both adjusted p< 0.001). Both guselkumab doses separated from placebo by week four.
At week 24, among patients with 3 percent or greater BSA psoriasis and IGA 2 or more at baseline, significantly more patients assigned to either guselkumab dose achieved IGA response versus placebo (both adjusted p< 0.001). Significantly greater improvements from baseline in HAQ-DI (adjusted p< 0.001) and SF-36 PCS (adjusted p≤0.011) were seen with both guselkumab doses versus placebo. Mean changes in total modified vdH-S scores were significantly lower for patients assigned to guselkumab every four weeks (0.29) and numerically lower for patients assigned to the drug every eight weeks (0.52) versus placebo (0.95; adjusted p=0.011 and p=0.072, respectively). Guselkumab every four weeks significantly reduced radiographic damage progression versus placebo.
Meanwhile, numerically larger mean improvements in SF-36 MCS scores with guselkumab every four week (4.22) and every eight weeks (4.17) were seen versus placebo (2.14; both adjusted p=0.072). Among pooled DISCOVER-1 and DISCOVER-2 patients with the condition at baseline, significantly higher proportions of patients assigned to guselkumab every four weeks and those assigned to the drug every eight weeks had resolved enthesitis or dactylitis versus placebo (all adjusted p< 0.05). Numerically higher proportions of patients assigned to either guselkumab dose than patients assigned to placebo with PASI75/90/100 (among patients with 3 percent or greater BSA psoriasis and IGA 2 or more at baseline) and MDA responses were observed.
Serious adverse events and serious infections occurred in 2.4 percent of patients assigned to guselkumab every four weeks and 0.7 percent of patients assigned to the drug every eight weeks, and no patients died.
“The safety data did not show unexpected results,” Professor Mease said. “There is a slight increase in infection compared to placebo.
“We anticipate that based on these results and the results of Discover 1, that in addition to approval for psoriasis, we will have approval of the use of this medicine for psoriatic arthritis.
“It is important for clinicians to have the ability to choose from several different medicines with different mechanisms of action in order to be able to target the various clinical domains of psoriatic arthritis and also because we know that not all patients will respond to a given medicine or have sustained response, so being able to choose and switch amongst effective choices is important,” Professor Mease said.
“L13- Guselkumab, an Anti-interleukin-23p19 Monoclonal Antibody, in Biologic-naïve Patients with Active Psoriatic Arthritis: Week 24 Results of the Phase 3, Randomized, Double-blind, Placebo-controlled Study.” Philip J. Mease, M.D., 9 a.m., Tuesday, Nov. 12. 2019 ACR/ARP Annual Meeting, Atlanta