Treatment with guselkumab, an interleukin-23 antagonist, was associated with significant improvements in joint and skin manifestations in patients with active psoriatic arthritis (PsA) with inadequate response to tumor necrosis factor inhibitors (TNFi), according to data from the phase 3b COSMOS study.
The randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT03796858) evaluated the efficacy and safety of guselkumab in 285 adults with active PsA who had an inadequate response to TNFis. Patients were randomly assigned 2:1 to receive guselkumab 100mg subcutaneously or placebo at week 0 and 4, then once every 8 weeks through week 44. Patients in the placebo arm switched to guselkumab treatment at week 24.
Results at week 24 showed that 44.4% (n=84/189) of patients treated with guselkumab met the primary endpoint, achieving an American College of Rheumatology (ACR) 20 response, compared with 19.8% (n=19/96) of those treated with placebo (adjusted difference, 24.6%; 95% CI, 14.1-35.2; P <.0001). Moreover, 54.9% of placebo-treated patients who crossed over to guselkumab at week 24 achieved an ACR20 response at week 48. Using nonresponder imputation, the ACR20 response rate in the guselkumab arm was 57.7% at week 48; more than 80% of week 24 responders maintained a response at week 48.
At week 24, the proportion of patients with at least 3% body surface psoriatic involvement and an Investigator’s Global Assessment (IGA) score of at least 2 at baseline who achieved complete skin clearance (Psoriasis Area Severity Index [PASI] 100) was significantly higher in the guselkumab arm (30.8%) vs the placebo arm (3.8%). At week 48, 53.4% of patients treated with guselkumab achieved complete skin clearance utilizing nonresponder imputation.
Statistically significant and clinically meaningful improvements were also observed in guselkumab-treated patients based on assessments of physical function, health-related quality of life, and fatigue.
“The COSMOS data demonstrate that [guselkumab] significantly improved signs and symptoms of active psoriatic arthritis across multiple clinical disease domains, including patient reported outcomes, with treatment effects observed by week 4,” said lead author Laura Coates, MD, PhD, Associate Professor, University of Oxford, UK. “These findings reinforce the utility of this alternative mechanism of action as a therapeutic option for adults with active psoriatic arthritis who have not responded to one or more therapies.”
Guselkumab is currently marketed under the brand name Tremfya® and is approved for the treatment of active psoriatic arthritis and moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
- Latest phase 3 data for first-in-class Tremfya® (guselkumab) demonstrates significant and durable improvement in signs and symptoms of active psoriatic arthritis while maintaining its safety profile in patients with inadequate response to tumor necrosis factor inhibition (TNFi-IR). News release. December 3, 2021. https://www.prnewswire.com/news-releases/latest-phase-3-data-for-first-in-class-tremfya-guselkumab-demonstrates-significant-and-durable-improvement-in-signs-and-symptoms-of-active-psoriatic-arthritis-while-maintaining-its-safety-profile-in-patients-with-inadequate-res-301437081.html?tc=eml_cleartime.
- 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 IIIb, randomised, controlled study (COSMOS). Annals of the Rheumatic Diseases. Published online November 24, 2021. doi: 10.1136/annrheumdis-2021-220991.