Background/Purpose: Fatigue is a key patient (pt)-reported symptom of psoriatic arthritis (PsA).^1,2 Utilizing data from the Phase 3 DISCOVER-1 (D1) and -2 (D2) studies, these post hoc analyses explored: 1) correlation of fatigue with systemic inflammation (CRP) and hemoglobin (Hgb); 2) relationship between improvements in fatigue and clinical outcomes with guselkumab (GUS), a selective IL-23p19 inhibitor.

Methods: Pts with active PsA despite standard therapies in D1 (swollen joint count [SJC] ≥3, tender joint count [TJC] ≥3, CRP ≥0.3 mg/dL) and D2 (SJC ≥5, TJC ≥5, CRP ≥0.6 mg/dL) were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or placebo (PBO) with crossover to GUS 100 mg Q4W at W24 (PBO͢àQ4W). Fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale (0–52 [higher score=less fatigue]; clinically meaningful improvement ≥4 points). FACIT-F scores, as well as their correlation (Pearson) with CRP and Hgb were determined in pts with anemia (Hgb < 13.5 [males] or < 12 [females] g/dL) and without anemia through W24. Relationships between FACIT-F score (outcome) and CRP/Hgb (predictors, along with visit) were assessed via a mixed model for repeated measures (MMRM). Associations between FACIT-F response in GUS-treated pts (Q4W+Q8W+PBOàQ4W) and achievement of American College of Rheumatology (ACR) 20/50/70, Health Assessment Questionnaire Disability Index (HAQ-DI), and Minimal Disease Activity (MDA) responses were evaluated at W52 for D1/D2 and at W100 for D2 (nonresponder imputation).

Results: In pooled analyses (N=1120), mean baseline (BL) FACIT-F scores for 583 males (31.3) and 537 females (28.5) were 3). Utilizing all pts pooled across treatment groups, significant correlations between FACIT-F scores and mean CRP/Hgb levels were seen at each visit (Table). Through W24, anemic pts had numerically lower FACIT-F scores (28.7-33.3) vs non-anemic pts (30.3-36.3). Among 112 pts with anemia at BL but not at W24, mean FACITF scores improved from 31 (W0) to 37 (W24). MMRM results showed that CRP and Hgb levels were statistically significant predictors of FACIT-F (each p< 0.0001; data not shown). GUS-treated pts achieving ≥4-point improvement in FACIT-F score at W52 (52-62% of 381 pts in D1 and 64-66% of 739 bio-naïve pts in D2) were more likely to also achieve ACR20/50/70, HAQ-DI, and MDA responses than FACIT-F nonresponders (D1 data not shown; D2 Figure). With continued GUS through W100, 65% of D2 pts with FACIT-F response showed an even stronger propensity than FACIT-F nonresponders for achieving ACR20 (odds ratio [OR]=8.2 [5.7, 11.8]), ACR50 (OR=5.9 [4.2, 8.3), ACR70 (OR=4.4 [3.0, 6.6]), HAQ-DI (OR=7.9 [5.5, 11.2]), and MDA (OR=3.4 [2.4, 4.8]) responses vs FACIT-F nonresponders (Figure).

Conclusion: In pts with active PsA, systemic inflammation and Hgb levels were key predictors of FACIT-F scores. FACIT-F responders were more likely to achieve favorable clinical outcomes through up to 2 years of GUS.

References

1. Leung YY, et al. J Rheumatol (Suppl) 2020;96:46-9.

2. Gudu T, et al. Joint Bone Spine 2016;83:439-43.

3. Montan I, et al. Value Health 2018;21:1313-21.

Table. Mean (SD) of FACIT-F Scores and CRP/Hgb Levels by Visit: Pooled DISCOVER_1 and _2 Studies

Figure. Achievement of ACR20/50/70, HAQ-DI, and MDA Responses by FACIT-F Response Status Among GUS-treated Patients at W52 and W100 of DISCOVER_2

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relationships-between-fatigue-and-hemoglobin-c-reactive-protein-levels-and-associations-between-fatigue-and-clinical-response-in-patients-with-active-psoriatic-arthritis-results-from-two-randomized-c/