Resolution of Enthesitis, Dactylitis with Guselkumab Linked to Durable Psoriatic Arthritis Improvements

Proton Raman, MD

Credit: ACR Convergence 2022

Biologic-naïve individuals with active psoriatic arthritis (PsA) given guselkumab treatment have durable patient-reported outcome (PRO) improvements associated with resolution of enthesitis and dactylitis, according to new findings.¹

The research team who ended up reporting these findings noted that PROs allow for essential information outside of the primary measures of disease measures. The team added that relief from fatigue and from pain are known priorities among PsA patients and that these 2 impacts are known to be higher among patients with concomitant enthesitis and/or dactylitis.^2,3

To look into these data among patients treated with guselkumab, the investigators used a post-hoc analysis of the DISCOVER-2 study. This new analysis was led by Proton Rahman, Memorial University of Newfoundland in Canada.

“In these post hoc analyses, we assessed associations between resolution of enthesitis and dactylitis among guselkumab-treated patients in the DISCOVER-2 study,” Raman and colleagues wrote. “Also, the correlations between resolution of enthesitis and/or dactylitis and meaningful improvements in PROs …were evaluated in guselkumab-treated patients through the end (2 years) of the DISCOVER-2 study.”

Background and Methods

The investigators conducted their post-hoc analysis of the DISCOVER-2 trial, a phase 3 trial which was carried out at several different centers and designed to assess guselkumab's use and safety among active PsA patients who were biologic-naïve. The study design was randomized, placebo-controlled, and double-blinded.

Participants in the study had been randomly assigned to be in 1 of 3 cohorts: those given guselkumab 100 mg injections at weeks 0, 4, and then every Q4W; those given guselkumab 100 mg at weeks 0, 4, then Q8W; or the placebo arm of the study. The study's final assessments took place at the 100th week.

The trial’s published eligibility criteria and study design were detailed in the prior study. In the investigators’ analysis, enthesitis and dactylitis among PsA patients were evaluated through the use of specific scoring systems by independent evaluators and done at distinct points in time points.

PROs were assessed by the research team, with such outcomes as reported pain, physical function, fatigue, and health-related quality of life (HRQoL) with the team using established tools. Connections were evaluated by the team between improvements in participant PROs and the lack of enthesitis or dactylitis using the statistical method of a Chi-squared test.

Findings

The PROs assessed by the investigators included pain as measured on a 0–100 visual analog scale, fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and physical function measured through the Health Assessment Questionnaire-Disability Index (HAQ-DI). They also evaluated HRQoL through a 36-item Short-Form Health Survey physical/mental component summary known as SF-36 PCS/MCS.

The team ended up with data on 739 participants who had been randomized and treated in DISCOVER-2. Specifically, there had been 245 in the Q4W dosing arm, 248 in the Q8W dosing arm, and 246 in the placebo arm.

Among individuals given guselkumab who experienced resolution of enthesitis, there was a much higher likelihood noted by the investigators of subjects reporting minimal pain (P < .001), normalized HAQ-DI scores (P < .001), and PCS response (P < .05) at the 24, 52, and 100-week marks compared to subjects that did not report resolution.

Additionally, those with resolved dactylitis were found by the research team to be more likely than those without to have gotten a response in their FACIT-Fatigue scores at the 24 and 52 week marks (both P ≤ .01). This was also true of minimal pain at 24 weeks and normalized HAQ-DI at 52 weeks (both P ≤ .03).

“While improvement in PROs would be expected to accompany resolution of these important aspects of disease, the distinct effects of the two manifestations on specific patient outcomes are noteworthy,” they wrote. “Future studies will provide insight into potential mechanisms impacting PROs and determining treatment choices by PsA phenotype.”

References

1. ^{Rahman, P., McInnes, I.B., Deodhar, A. et al. Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis. Clin Rheumatol (2024). https://doi.org/10.1007/s10067-024-06921-8.}
2. ^{Mease PJ, Karki C, Palmer JB, Etzel CJ, Kavanaugh A, Ritchlin CT et al (2017) Clinical characteristics, disease activity, and patient-reported outcomes in psoriatic arthritis patients with dactylitis or enthesitis: results from the CORRONA Psoriatic Arthritis/Spondyloarthritis Registry. Arthritis Care Res (Hoboken) 69(11):1692–1699.}
3. ^{Mease PJ, Liu M, Rebello S, Hua W, McLean RR, Hur P et al (2021) Disease characteristics, quality of life, and work productivity by enthesitis site: real-world data from the US CORRONA Psoriatic Arthritis/Spondyloarthritis Registry. J Rheumatol 48(3):367–375.}