Background/Purpose: The IL-23p19-subunit inhibitor guselkumab (GUS) demonstrated clinically meaningful improvements in fatigue through one year of treatment¹ independent of its effects on ACR20 and MDA achievement². In this post hoc analysis, the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) scale was used to: (a) evaluate the long-term effect of GUS in maintaining improvements in or further improving fatigue between week (W) 52 and W100, and to; (b) identify potential early (W8) predictors, in terms of fatigue, for improved long-term fatigue outcomes.

Methods: DISCOVER-2 enrolled adult patients (pts) with active PsA (≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dl) who were naïve to biologics/JAK inhibitors. Pts were randomized (1:1:1) and treated with GUS 100 mg every 4W (Q4W); GUS 100mg at W0, W4, then Q8W; or placebo (PBO→GUS Q4W; crossing over to GUS Q4W at W24). Pts with baseline (BL) fatigue levels lower than the normative value (FACIT-F score ≤43)³ were included in these post hoc analyses (N=681). The proportions of pts with clinically meaningful improvement (≥4 points) from BL in FACIT-F and with normative FACIT-F levels between W52 and W100 were calculated using non-responder imputation (NRI) for missing data and compared over time within each treatment group with the McNemar test. Changes in FACIT-F over time were assessed with mixed models adjusting for time, treatment group, their interaction, and BL FACIT-F score. Receiver operating characteristics (ROC) analyses were conducted using Youden’s index to determine optimal cutoffs at W8 for predicting achievement of normative scores and clinically meaningful FACIT-F responses at W100.

Results: At BL, the mean (SD) FACIT-F score was 28.3 (8.7) with similar levels across treatment groups. At W52, 66.1%, 69.6%, 68.0%, and 67.8% of pts in the PBO→GUS Q4W, GUS Q4W, GUS Q8W, and pooled GUS groups, respectively, achieved clinically meaningful improvements from BL in FACIT-F score; response rates were maintained through W100 (Figure 1a). Normative FACIT-F levels were achieved by 24.9%, 28.1% 29.4% and 27.5% of pts in each treatment group, respectively, at W52, and by increasingly greater proportions of pts through W100 (Figure 2b). Significant improvements from BL in FACIT-F scores were observed at W52 (all nominal p< 0.05), with further improvements seen from W52 to W100 across all GUS groups (Figure 2). ROC optimal cutoff in FACIT-F improvement from BL to W8 associated with a clinically meaningful improvement in FACIT-F at W100 was ≥2.0 (nominal p< 0.0001); while for achieving normative FACIT-F levels at W100, the optimal cutoff in actual FACIT-F score at W8 was ≥39.5 (nominal p< 0.0001) (Figure 3).

Conclusion: The clinically meaningful improvements in fatigue seen after 1 year of GUS treatment were further enhanced through 2 years, at which time nearly a third of GUS-treated pts reported normative FACIT-F levels. Early targets in FACIT-F levels achieved with GUS were identified to aid in guiding treatment decisions in routine clinical practice.

References:
1. Ritchlin CT et al. RMD Open. 2022 Mar;8(1);e002195.
2. Rahman P et al. Arthritis Res Ther. 2021 Jul 14;23(1):190.
3. Montan I et al. Value Health. 2018 Nov;21(11):1313-1321.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-efficacy-of-guselkumab-in-fatigue-and-identification-of-early-treatment-targets-post-hoc-analysis-through-2-years-of-a-phase-3-randomized-double-blind-placebo-controlled-study-conducted/