Efficacy of guselkumab on axial involvement in patients with active psoriatic arthritis and sacroiliitis: a post-hoc analysis of the phase 3 DISCOVER-1 and DISCOVER-2 studies

Mease, P.J.; Helliwell, P.S.; Gladman, D.D.; Poddubnyy, D.; Baraliakos, X.; Chakravarty, S.D.; ... ; Heijde, D. van der (2021)

Article / Letter to editor

Background Guselkumab was efficacious in reducing signs and symptoms of psoriatic arthritis in the phase 3 DISCOVER-1 and DISCOVER-2 studies. We aimed to evaluate the efficacy of guselkumab in post-hoc analyses of patients with psoriatic arthritis with imaging-confirmed sacroiliitis consistent with axial involvement. Methods In DISCOVER-1, 381 patients with active psoriatic arthritis (defined as 03 swollen joints, 03 tender joints, and C-reactive protein [CRP] 00middot3 mg/dL) and in DISCOVER-2, 739 patients with active psoriatic arthritis (defined as 05 swollen joints, 05 tender joints, and CRP 00middot6 mg/dL) were randomly allocated to receive guselkumab 100 mg every 4 weeks, guselkumab 100 mg every 8 weeks (week 0, week 4, then every 8 weeks), or placebo. These pooled, post-hoc analyses included patients with axial disease documented by previous imaging or pelvic radiography at screening consistent with sacroiliitis (confirmed by investigator). Efficacy assessments included least squares mean changes, with 95% CIs, in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, modified BASDAI (mBASDAI; excluding peripheral joint pain), spinal pain, and Ankylosing Spondylitis Disease Activity Score (ASDAS), and proportions of patients achieving at least a 50% improvement in BASDAI score (BASDAI50) and achieving ASDAS responses of inactive disease (score <1middot3), major improvement (change of 02middot0), and clinically important improvement (change of 01middot1). Findings Of the 1120 patients in the two DISCOVER studies, 312 (28%) were included in this analysis, of whom 118 were in the placebo group, 103 were in the guselkumab every 4 weeks group, and 91 were in the guselkumab every 8 weeks group. 191 (61%) were male, and 121 (39%) were female, and the mean age was 45middot1 (SD 11middot2). HLA-B27 status was assessed in 190 patients; 57 (30%) were HLA-B27-positive and 133 (70%) were HLA-B27-negative. At week 24, least squares mean changes from baseline in BASDAI were -2middot7 (95% CI -3middot2 to -2middot2) in both guselkumab groups versus -1middot3 (-1middot8 to -0middot9) in the placebo group; similar results were observed for mBASDAI and spinal pain. Least squares mean changes in ASDAS scores at week 24 were -1middot4 (95% CI -1middot7 to -1middot2) in both guselkumab groups and -0middot7 (-0middot9 to -0middot5) for placebo. At week 24, 36 (38%) patients in the guselkumab every 4 weeks group and 34 (40%) of those in the guselkumab every 8 weeks group achieved BASDAI50 versus 21 (19%) of placebo patients; greater proportions of guselkumab-treated patients achieved ASDAS responses versus placebo. Across outcomes, separation from placebo was observed at week 8. Improvements with guselkumab were seen at week 24 independent of HLA-B27 status. These improvements were maintained at week 52 in the guselkumab groups. Interpretation Patients with active psoriatic arthritis and imaging-confirmed sacroiliitis who were treated with guselkumab every 4 weeks or every 8 weeks had greater mean improvements in BASDAI and ASDAS (as early as week 8) than did placebo-treated participants, with sustained improvements at week 52. Funding Janssen Research & Development LLC. Copyright (c) 2021 Elsevier Ltd. All rights reserved.

• All authors: Mease, P.J.; Helliwell, P.S.; Gladman, D.D.; Poddubnyy, D.; Baraliakos, X.; Chakravarty, S.D.; Kollmeier, A.P.; Hsia, E.C.; Xu, X.L.; Sheng, S.H.; Agarwal, P.; Zhou, B.; Sweet, K.; Shawi, M.; Karyekar, C.S.; Deodhar, A.; Heijde, D. van der
• Date: 2021-10-01
• Journal: LANCET RHEUMATOLOGY
• Volume: 3
• Issue: 10
• Pages: E715 - E723
• DOI: doi:10.1016/ S2665-9913(21)00105-3