Early Improvement in 3vas/4vas Predicts Reduced Rates of Radiographic Change in Bio-naive Active Psoriatic Arthritis Patients Receiving Guselkumab Treatment

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Tillett, W
Coates, L
Vis, M
Soriano, E
Merola, JF
Zimmermann, M
Shawi, M
Sharaf, M
Nash, P
Helliwell, P
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2023
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Milan, Italy

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Abstract

Background Guselkumab (GUS), a fully human IL-23p19 subunit inhibitor, was shown to reduce mean changes in radiographic progression vs placebo (PBO) by week (W)24 [1] and to be associated with low rates of radiographic progression through W100 among GUS-treated patients (pts) with PsA, irrespective of dosing regimen (every [Q] 4W or Q8W) [2] Furthermore, earlier clinical response predicted improved long-term radiographic outcome in GUS-treated pts with active PsA [3]. The recently developed 3 Visual Analogue Scale (VAS) and 4 VAS scores are the first short multidimensional composite measures specifically for use in PsA routine clinical care [4].

Objectives Determine whether early improvement in 3VAS/4VAS predicts radiographic change through W100.

Methods DISCOVER-2 included biologic-naïve pts with active PsA (≥5 swollen and ≥5 tender joint counts [SJC/TJC]; CRP ≥0.6 mg/dL) randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W at W24. In the current analysis, only pts randomized to GUS were included (N=493), pooling Q4W and Q8W. Response at W8 was defined as achievement of low disease activity (LDA) in 3VAS (≤3.4), 4VAS (≤3.5), RAPID3 (≤6), DAPSA (≤14), and PASDAS (≤3.2). Association of W8 response with change from baseline (BL) to W100 in total PsA-modified van der Heijde-Sharp [vdH-S] score was assessed with the independent samples t-test and generalized linear models adjusting for known BL determinants of radiographic progression (vdH-S score, age, gender, and CRP). Pairwise correlations and agreement in LDA classification between the endpoints assessed were assessed with Pearson’s correlation coefficient and the kappa statistic, respectively.

Results Among GUS-treated pts not meeting the respective endpoints at BL, 32.9%, 31.6%, 12.4%, 17.8%, and 10.8% achieved LDA in 3VAS, 4VAS, RAPID3, DAPSA, and PASDAS, respectively, at W8. LDA achievement in 3VAS (0.86 vs. 2.15, p=0.03), RAPID3 LDA (0.74 vs. 1.80, p=0.049), DAPSA LDA (-0.05 vs. 2.08, p<0.001), and PASDAS LDA (0.58 vs. 1.87, p=0.006) at W8 were associated with significantly less radiographic progression through W100 (Figure 1). For 4VAS, achievement of remission (≤2.1; 0.71 vs. 1.84, p=0.045), but not LDA (1.12 vs. 2.01, p=0.142), was also associated with improved radiographic outcome. In multivariate analyses, improved response to GUS treatment at W8 in all endpoints assessed was associated with numerically less radiographic progression through W100. 3VAS and 4VAS at W8 showed strong correlations with RAPID3 (r3VAS=0.787; r4VAS=0.877) and PASDAS (r3VAS=0.795; r4VAS=0.790) and moderate correlations with DAPSA (r3VAS=0.466; r4VAS=0.524), whereas fair to moderate agreement (kappa range: 0.325-0.545) in LDA classification was noted.

Conclusion Approximately one-third of GUS-treated patients achieved early response (W8 LDA) in 3VAS/4VAS, which was associated with reduced rates of radiographic change, as was early response in the other outcomes assessed. These results suggest that, in addition to their usefulness in assessing disease activity in routine clinical care, 3VAS and 4VAS, the former being more sensitive, may predict long-term radiographic changes.

References [1]Mease PJ, et al. Lancet. 2020;395:1126–36

[2]McInnes IB, et al. Arthritis Rheumatol. 2022;74:475-85

[3]Mease PJ, et al. Ann Rheum Dis. 2022;81:828-29

[4]Tillett W, et al. J Rheumatol. 2021;jrheum.201675

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EULAR 2023 European Congress of Rheumatology, 31 May - 3 June. Milan, Italy

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82

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Suppl 1

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Clinical sciences

Immunology

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Life Sciences & Biomedicine

Rheumatology

Psoriatic arthritis

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Tillett, W; Coates, L; Vis, M; Soriano, E; Merola, JF; Zimmermann, M; Shawi, M; Sharaf, M; Nash, P; Helliwell, P, Early Improvement in 3vas/4vas Predicts Reduced Rates of Radiographic Change in Bio-naive Active Psoriatic Arthritis Patients Receiving Guselkumab Treatment, Annals of the Rheumatic Diseases, 2023, 82 (Suppl 1), pp. 1131-1132