Guselkumab provides sustained domain-specific and comprehensive efficacy using composite indices in patients with active psoriatic arthritis

Laura C Coates, Christopher T Ritchlin, Laure Gossec, Philip S Helliwell, Proton Rahman, Alexa P Kollmeier, Xie L Xu, May Shawi, Chetan S Karyekar, Christine Contré, Wim Noël, Shihong Sheng, Yanli Wang, Stephen Xu, Philip J Mease, Laura C Coates, Christopher T Ritchlin, Laure Gossec, Philip S Helliwell, Proton Rahman, Alexa P Kollmeier, Xie L Xu, May Shawi, Chetan S Karyekar, Christine Contré, Wim Noël, Shihong Sheng, Yanli Wang, Stephen Xu, Philip J Mease

Abstract

Objectives: To evaluate the efficacy of guselkumab for the treatment of active PsA utilizing composite indices.

Methods: Data were pooled from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies. In both studies, patients were randomized 1:1:1 to subcutaneous guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then Q8W; or placebo Q4W with crossover to guselkumab 100 mg Q4W at week 24. Composite indices used to assess efficacy through week 52 included Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA), and very low disease activity (VLDA). Through week 24, treatment failure rules were applied. Through week 52, non-responder imputation was used for missing data.

Results: Greater proportions of guselkumab- than placebo-treated patients achieved DAPSA low disease activity (LDA) and remission, PASDAS LDA and VLDA, MDA, and VLDA at week 24 vs placebo (all unadjusted P < 0.05). At week 52, in the guselkumab Q4W and Q8W groups, respectively, response rates were as follows: DAPSA LDA, 54.2% and 52.5%; DAPSA remission, 18.2% and 17.6%; PASDAS LDA, 45.3% and 41.9%; PASDAS VLDA, 16.9% and 19.5%; MDA, 35.9% and 30.7%; and VLDA, 13.1% and 14.4%. In the placebo-crossover-to-guselkumab group, response rates for all composite indices increased after patients switched to guselkumab, from week 24 through week 52.

Conclusion: Treatment with guselkumab provided robust and sustained benefits across multiple PsA domains through 1 year, indicating that guselkumab is an effective therapy for the diverse manifestations of PsA.

Trial registration: NCT03162796; NCT03158285.

Keywords: PsA; composite indices; guselkumab; joint disease; remission; skin clearance.

© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig. 1
Fig. 1
Achievement of DAPSA LDA, cDAPSA LDA, PASDAS LDA, and MDA (A) DAPSA LDA; (B) cDAPSA LDA; (C); PASDAS LDA; (D) MDA. Through week 24, patients meeting treatment failure criteria or with missing data were considered non-responders. Treatment group comparisons through week 24 were not adjusted for multiplicity of testing. After week 24 and through week 52, patients with missing data were considered non-responders. *P < 0.001, vs PBO (nominal). cDAPSA: clinical DAPSA (excludes CRP); DAPSA: Disease Activity in Psoriatic Arthritis; GUS: guselkumab; LDA: low disease activity; MDA: minimal disease activity; PASDAS: Psoriatic Arthritis Disease Activity Score; PBO: placebo; Q4W: every 4 weeks; Q8W: every 8 weeks.
Fig. 2
Fig. 2
Achievement of DAPSA remission, cDAPSA remission, PASDAS VLDA, and VLDA (A) DAPSA remission; (B) cDAPSA remission; (C) PASDAS VLDA; (D) VLDA. Through week 24, patients meeting treatment failure criteria or with missing data were considered non-responders. Treatment group comparisons through week 24 were not adjusted for multiplicity of testing. After week 24 and through week 52, patients with missing data were considered non-responders. *P < 0.05, +P < 0.01, ‡P < 0.001, vs PBO (nominal). cDAPSA: clinical DAPSA (excludes CRP); DAPSA: Disease Activity in Psoriatic Arthritis; GUS: guselkumab; PASDAS: Psoriatic Arthritis Disease Activity Score; PBO: placebo; Q4W: every 4 weeks; Q8W: every 8 weeks; VLDA: very low disease activity.
Fig. 3
Fig. 3
Maintenance of LDA (A) and remission (B) at week 52 among week-24 responders (guselkumab-randomized patients) n represents the total number of patients with response at week 24. Through week 24, patients meeting treatment failure criteria or with missing data were considered non-responders. After week 24 and through week 52, patients with missing data were considered non-responders. DAPSA: Disease Activity Index for Psoriatic Arthritis; GUS: guselkumab; LDA: low disease activity; MDA: minimal disease activity; PASDAS: Psoriatic Arthritis Disease Activity Score; Q4W: every 4 weeks; Q8W: every 8 weeks; VLDA: very low disease activity.
Fig. 4
Fig. 4
Mean vdH-S score changes by week 24 PASDAS LDA, DAPSA LDA, and MDA response (DISCOVER-2) Evaluable patients had an observed change from baseline to week 52 in PsA-modified vdH-S score and observed PASDAS, DAPSA, or MDA status, respectively, at week 24. DAPSA: Disease Activity Index for Psoriatic Arthritis; LDA: low disease activity; MDA: minimal disease activity; PASDAS: Psoriatic Arthritis Disease Activity Score; Q4W: every 4 weeks; Q8W: every 8 weeks; vdH-S: van der Heijde–Sharp.
Fig. 5
Fig. 5
Achievement of ≤1 tender joint, patient assessment of pain VAS ≤15, HAQ-DI score ≤0.5, and PtGA ≤20 (A) ≤1 tender joint; (B) VAS ≤15; (C) HAQ-DI ≤0.5; (D) PtGA ≤20. Through week 24, patients meeting treatment failure criteria or with missing data were considered non-responders. Treatment group comparisons through week 24 were not adjusted for multiplicity of testing. After week 24 and through week 52, patients with missing data were considered non-responders. *P < 0.05, +P < 0.01, ‡P < 0.001, vs PBO (nominal). GUS: guselkumab; HAQ-DI: HAQ-Disability Index; PBO: placebo; PtGA: patient global assessment of disease activity (arthritis and psoriasis); Q4W: every 4 weeks; Q8W: every 8 weeks; VAS: visual analogue scale.

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