WASHINGTON – The investigational anti-interleukin-23 monoclonal antibody guselkumab was safe and well tolerated, and demonstrated significant improvement on a variety of measures in patients with active psoriatic arthritis in a randomized, placebo-controlled phase IIa study.
The primary endpoint of ACR20 at 24 weeks was achieved in 58% of 100 patients randomized to receive treatment with guselkumab versus 18.4% of 49 patients who received placebo, Atul A. Deodhar, MD, reported in a late-breaking abstract presentation at the annual meeting of the American College of Rheumatology.
Mitchel L. Zoler/Frontline Medical News
Dr. Atul A. Deodhar
For example, PASI75 response at 24 weeks was 78.6% for guselkumab and 12.5% for placebo, and the ACR50 response at 24 weeks was 34% vs. 10.2%, respectively. The HAQ-DI score mean change from baseline was –0.42 vs. –0.06, respectively.
Further, ACR20 response was seen as early as week 4 (21% vs. 0% for placebo), and the effect increased over time, reaching the maximum effect by week 16 (60% vs. 16.3%), Dr. Deodhar said.
Subjects in the double-blind, multicenter study had active psoriatic arthritis and at least 3% body surface area of plaque psoriasis despite treatment with standard-of-care therapies. Patients with prior exposure to anti–tumor necrosis factor–alpha agents were included. They received either 100 mg guselkumab delivered subcutaneously or placebo at week 0 and 4, then every 8 weeks thereafter through week 44.
Patients with less than 5% improvement in swollen and tender joint count at week 16 were allowed early escape to open-label ustekinumab (Stelara), and at week 24 all remaining patients crossed over to receive guselkumab, which was repeated at week 28 and every 8 weeks thereafter through week 44.
Treatment was well tolerated; the proportion of patients with one or more adverse events was similar in the treatment and placebo groups (36% and 32.7%, respectively), with infections being the most common adverse event, occurring in 17% and 20.4% of patients in the groups, respectively.
“And even though 10% and 14% of the patients received systemic treatment, no patient received [intravenous] antibiotics,” he said.
Severe adverse events occurred in two patients – one in each group – and included a knee injury and myocardial infarction. Specific information about which group these occurred in is not available as the study is ongoing and investigators remain blinded, Dr. Deodhar noted.
No serious infections, malignancies, or deaths occurred through week 24, he said.
“Guselkumab is the first anti-IL23 biologic to demonstrate efficacy in psoriatic arthritis. In patients with active psoriatic arthritis ... treatment with guselkumab shows significant improvements in joint symptoms, physical function, psoriasis, enthesitis, dactylitis, and quality of life,” he concluded, adding that there were no unexpected safety findings in this population.
On Nov. 17, Janssen Biotech, Inc. announced the submission of a Biologics License Application to the Food and Drug Administration seeking approval of guselkumab for the treatment of adults with moderate to severe plaque psoriasis based on findings from prior studies for that indication.
The current study was sponsored by Janssen Research & Development. Dr. Deodhar reported financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer, and UCB. Two other authors also reported financial ties to industry, including Janssen. Four of the seven authors of the abstract were employees of Janssen.