NEW YORK (Reuters Health)—In patients with psoriatic arthritis (PsA) who are resistant to tumor necrosis factor inhibitors (TNFi), guselkumab was more effective than placebo in a phase 3b trial.
“Guselkumab is a relatively new treatment and is the first drug in its class (IL-23 inhibitor) to gain approval for PsA,” Dr. Laura Coates of the University of Oxford, UK, told Reuters Health by email. “Previous studies (the DISCOVER trials) showed that it was effective for peripheral musculoskeletal disease (arthritis, enthesitis, dactylitis) in addition to known efficacy in skin/nail psoriasis from dermatology studies.”
“The majority of patients in the DISCOVER trials were receiving guselkumab as their first biologic,” she noted. “A lot of the unmet need in the clinic now, is patients who have previously been treated with other biologics but have not responded or have lost response to another treatment.”
“This study tested guselkumab in patients who have previously been treated with 1-2 TNF inhibitors, (and it) showed efficacy and safety similar to the previous DISCOVER trials,” she said.
As reported in the Annals of the Rheumatic Diseases, Dr. Coates and colleagues evaluated the efficacy and safety of guselkumab in 285 adults with active PsA (3 or more swollen and 3 or more tender joints) who discontinued up to two TNFi due to inadequate response (IR; lack of efficacy or intolerance).1
Overall, about 90% of participants had a mean age of 49; about half were women; and most had been on one (88%) or two (12%) prior TNFi.
Participants were randomized (2:1) to 100 mg subcutaneous guselkumab or placebo at week 0, week 4, then every 8 weeks through week 44. Those receiving placebo crossed over to guselkumab at week 24.
Eighty-eight percent of patients on guselkumab and 86% of those on placebo to guselkumab completed the study through week 44.
A significantly higher proportion of patients receiving guselkumab (44.4%) versus placebo (19.8%) achieved ACR20 at week 24.
In addition, guselkumab was superior to placebo for each key secondary endpoint: change in the Health Assessment Questionnaire-Disability Index, ACR50, change in the 36-item Short-Form Health Survey physical and mental component summary, and the Psoriasis Area and Severity Index 100.
The ACR20 response (non-responder imputation) in the guselkumab group was 58% at week 48, with >80% of week 24 responders maintaining response at that point.
Through week 24, serious adverse events/serious infections occurred in 3.7%/0.5% of guselkumab patients and 3.1%/0% of placebo patients, and the guselkumab safety profile was similar through week 56.
No deaths or opportunistic infections occurred.
The authors note that self-administration was permitted during the COVID-19 pandemic, when site visits were restricted, resulting in some major protocol deviations. However, they state, “These were classified mostly as drug administration or study visit missed or outside of the prespecified window, and most were considered to have no effect on efficacy assessments.”
Dr. Coates says, “This drug has now been licensed for treatment of patients with PsA and this study supports use in those who have previously been treated with other biologics.”
“Next steps would include observational ‘real-world’ data in patients in the clinic,” she adds. “This would support data on efficacy/safety in a wider population, as not all patients are eligible or willing to join clinical trials,” she adds. “The efficacy seen in arthritis, enthesitis and dactylitis, as well as skin disease also leads to a significant benefit in terms of functional ability and quality of life.”
Dr. Soumya Chakravarty, Senior Director, Strategic Lead, Rheumatology Therapeutic Area at Janssen Scientific Affairs, LLC, commented in an email to Reuters Health, “Results from this study provide further evidence that [guselkumab] is effective in treating patients with various manifestations of active psoriatic arthritis even when TNF inhibitor treatment has failed.”
The study was sponsored by Janssen Research and Development, LLC. Four coauthors are employees and Dr. Coates and other coauthors have received funds from the company.
Reference
- Coates LC, Gossec L, Theander E, et al. Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase 3b, randomised, controlled study (COSMOS). Ann Rheum Dis. 2021 Nov 24;annrheumdis-2021-220991. Online ahead of print.
