COSMOS: Guselkumab improves response rates in active psoriatic arthritis

Treatment with guselkumab improved response rates in patients with active psoriatic arthritis (PsA) who had inadequate responses to tumour necrosis factor (TNF) inhibitors, according to the COSMOS* study presented at EULAR 2021.

Participants in this phase IIIb, double-blind, multicentre trial were 285 patients (mean age 49 years) with PsA (≥3 swollen and ≥3 tender joints for ≥6 months) who had inadequate response or tolerance to one or two TNF inhibitors. Participants were randomized in a 2:1 ratio to receive subcutaneous guselkumab 100 mg (n=189) at weeks 0 and 4, then every 8 weeks, or placebo at weeks 0, 4, and 20 (n=96). Placebo recipients were crossed over to receive guselkumab at week 24 through week 48. [EULAR 2021, abstract OP0230]

At week 24, significantly more patients treated with guselkumab than placebo experienced ACR20** response (44.4 percent vs 19.8 percent; p<0.001 adjusted for multiplicity of testing). “[This] treatment effect [was] seen as early as week 4,” said lead author Dr Laura Coates from the University of Oxford, Oxford, UK.

This benefit of guselkumab vs placebo at week 24 was consistent across all subgroups of patients, disease characteristics, and prior and concomitant medications (44.4 percent vs 19.8 percent; odds ratio, 3.2 for all).

Following the crossover of placebo recipients to guselkumab at week 24, ACR20 response rates at week 48 were similar between the guselkumab and placebo arms (57.7 percent vs 54.9 percent).

Guselkumab-treated patients demonstrated a significantly greater improvement in physical function (least squares [LS] mean change in HAQ-DI*** score, -0.18 vs -0.01; p=0.003) and health-related quality of life (LS mean change in SF-36 PCS⁺ score, 3.51 vs -0.39; p<0.001) compared with placebo-treated patients at week 24, and with further improvement at week 48 or 1 year.

A significantly higher percentage of patients on guselkumab experienced complete skin clearance, as indicated by an increase in PASI 100⁺⁺ response rate, than those on placebo at week 24 (30.8 percent vs 3.8 percent; p<0.001), with a continuous increase at week 48 or 1 year (53.4 percent vs 39.1 percent).

Patients on guselkumab also showed higher rates of resolution of enthesitis and dactylitis than those on placebo at week 24 (39.7 percent vs 18.8 percent and 44.8 percent vs 25.0 percent, respectively), with increased resolution rates at week 48 or 1 year.

“[Overall,] guselkumab was superior to placebo for all major secondary endpoints,” said Coates.

Adverse event rates did not increase through 1 year of treatment with guselkumab, with no opportunistic infection, active tuberculosis, or anaphylactic/serum sickness-like reactions reported. There were also no confirmed cases of inflammatory bowel disease or death, said Coates.

“[In conclusion,] guselkumab elicited a significantly higher ACR20 response rate vs placebo at week 24 … [through 1 year, suggesting] a durable and broad impact of targeting the p19 subunit of IL-23 in PsA patients who previously had an inadequate response to one or two TNF inhibitors,” said Coates.

“In this population, guselkumab was well tolerated and demonstrated a favourable benefit-risk profile … that was consistent with the established safety profile in psoriasis and PsA guselkumab studies,” Coates added.

*COSMOS: A study of guselkumab in participants with active psoriatic arthritis and an inadequate response to anti-tumor necrosis factor alpha (anti-TNF alpha) therapy

**ACR20: American College of Rheumatology 20 percent improvement in swollen and tender joint count

***HAQ-DI: Health Assessment Questionnaire-Disability Index

⁺SF-36 PCS: Short form Health Survey Physical Component Summary

⁺⁺PASI 100: Psoriatic Area and Severity Index 100