Guselkumab 100 mg Every 8 Weeks Consistently Improves Joint, Skin Through Week 24

A study showed guselkumab every 8 weeks led to consistent improvements through week 24 in joint, skin, patient-reported outcomes, and composite outcomes in patients with psoriatic arthritis (PsA) compared with placebo.1

“These post hoc analyses of the COSMOS trial were conducted to explore the effect of guselkumab versus placebo at week 24, and the maintenance of response through 48 weeks in the guselkumab group, across multiple PsA domains in subgroups of patients with PsA and TNFi-IR,” wrote investigators, led by Iain B. McInnes, MBChB, from College of Medical Veterinary and Life Sciences at University of Glasgow, in the UK. “We found that guselkumab treatment resulted in greater response rates, compared with placebo, in this population, regardless of baseline demographics, disease characteristics or prior/ongoing therapies.”

Factors known to reduce the response to PsA treatment include female sex, obesity, longer disease duration, more severe skin involvement, lower levels of CRP, a history of TNFi-IR, and ongoing use of csDMARDs.2,3,4

Investigators sought to investigate the effect of guselkumab though 48 weeks in several subgroups of patients with PsA, including those who had an inadequate response to tumor necrosis factor inhibitors (TNFi-IR) from the phase 3b COSMOS trial.1 PsA was defined as a tender joint count and swollen joint count of ≥ 3.

Participants were randomized 2:1 to receive guselkumab 100 mg at week 0, week 4, and then every 8 weeks through week 44 (n = 189), or to placebo (n = 96) where participants still received guselkumab 100 mg at week 16 or week 24. The sample included 24% patients who were ≥ 60 years old at baseline, 52% females, 41% with a BMI ≥ 30 kg/m2, 51% had a PsA duration ≥ 6 years, and 12% had prior TNFi at baseline. Additionally, 63% of patients had a swollen joint count of < 10 and 57% had a tender joint count > 15.

The team evaluated guselkumab’s effect on joints, skin, patient-reported outcomes, and composite outcome measures through the following assessments:

Joints: American College of Rheumatology (ACR) 20/50/70, enthesitis, dactylitis

Skin: Psoriasis Area and Severity Index 90/100, Investigator’s Global Assessment 0/1

Patient-reported outcomes: Functional Assessment of Chronic Illness Therapy–Fatigue, Health Assessment Questionnaire–Disability Index)

Composite outcome measures: PsA Disease Activity Score low disease activity, minimal disease activity

During the examination, investigators accounted for baseline age, sex, BMI, swollen joint count, tender joint count, PsA duration, percentage of body surface area, C reactive protein, pain Visual Analogue Scale, number of prior TNFi and discontinuation reason, and conventional synthetic disease-modifying antirheumatic drug status. Investigators observed similar baseline characters for patients on guselkumab and placebo.

Furthermore, investigators observed greater improvement in joints among participants on guselkumab versus placebo, seen by the response rates of ACR 20 (50% vs 28%; odds ratio [OR], 1.5 to 4.6) and ACR 50 (23% vs 8%; OR, 3.2; 95% CI, 1.4 to 8.3) at week 24. The guselkumab group had increased response rates from week 24 to week 48 with nearly all subgroups, including patient age (ORs, 2.3 – 3.8), sex (ORs, 1.9 – 3.5), BMI (ORs, 2.4 –2.6).

Guselkumab was also more effective than placebo within patient subgroups categized by baseline SJC (ORs, 2.3 – 3.4), TJC (ORs, 1.5 – 4.1), PsA duration (ORs, 1.8 – 6.6), percentage of BSA (ORs, 1.6 – 4.2), CRP level (ORs, 1.9 –4 .6), or pain VAS (ORs, 2.4 – 3.1). Patients on guselkumab had greater response rates than those on placebo for achieving enthesitis resolution (47% vs 23%; OR, 2.9; 95% CI 1.4 to 6.1) and dactylitis resolution (57% vs 36%; OR, 2.3; 95% CI 0.9 to 5.9) at week 24. In general, patients with guselkumab had numerically greater response rates than those treated with placebo.

“While trends or differences in response rates were noted within some subgroups, the study was not statistically powered to provide a meaningful evaluation of these differences,” investigators wrote.

References

1. McInnes IB, Sewerin P, Sharaf M, Efficace M, Lavie F, Zimmermann M, Coates LC. Sustained response to guselkumab regardless of baseline characteristics in patients with active psoriatic arthritis and inadequate response to TNF inhibitors: results from the phase 3b COSMOS clinical trial. RMD Open. 2024 Dec 12;10(4):e004494. doi: 10.1136/rmdopen-2024-004494. PMID: 39672591.
2. Passia E, Vis M, Coates LC, et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther 2022;24:22. doi:10.1186/s13075-021-02680-yGoogle Scholar
3. Kumthekar A, Ogdie A. Obesity and psoriatic arthritis: a narrative review. Rheumatol Ther 2020;7:447–56. doi:10.1007/s40744-020-00215-6Google Scholar
4. Navarini L, Costa L, Tasso M, et al. Retention rates and identification of factors associated with anti-TNFα, anti-IL17, and anti-IL12/23R agents discontinuation in psoriatic arthritis patients: results from a real-world clinical setting. Clin Rheumatol 2020;39:2663–70. doi:10.1007/s10067-020-05027-1Google Scholar