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.

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 ≥3 swollen joints, ≥3 tender joints, and C-reactive protein [CRP] ≥0·3 mg/dL) and in DISCOVER-2, 739 patients with active psoriatic arthritis (defined as ≥5 swollen joints, ≥5 tender joints, and CRP ≥0·6 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 <1·3), major improvement (change of ≥2·0), and clinically important improvement (change of ≥1·1).
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 45·1 (SD 11·2). 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 -2·7 (95% CI -3·2 to -2·2) in both guselkumab groups versus -1·3 (-1·8 to -0·9) in the placebo group; similar results were observed for mBASDAI and spinal pain. Least squares mean changes in ASDAS scores at week 24 were -1·4 (95% CI -1·7 to -1·2) in both guselkumab groups and -0·7 (-0·9 to -0·5) 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.
Competing Interests: Declaration of interests PJM reports grants and personal fees from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, and personal fees from Boehringer Ingelheim and GlaxoSmithKline. PSH reports grants, personal fees, and non-financial support from Abbvie; grants and personal fees from Janssen; grants from Pfizer; and personal fees from Galapagos and Novartis. DDG reports grants and personal fees from Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, and personal fees from Bristol Myers Squibb, Galapagos, and Gilead. DP reports grants and personal fees from AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, and Pfizer, and personal fees from Biocad, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Roche, and UCB. XB reports grants and personal fees from AbbVie and Novartis, and personal fees from Bristol Myers Squibb, Celgene, Chugai, Galapagos, Gilead, Merck Sharp & Dohme, Pfizer, and UCB. AD has received grants and personal fees from Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB, and personal fees from AbbVie, Amgen, and Boehringer Ingelheim. DvdH reports personal fees from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daichii, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma, and is the Director of Imaging Rheumatology BV. APK, ECH, XLX, SS, PA, BZ, and KS are employed by Janssen Research & Development LLC, SDC is employed by Janssen Scientific Affairs LLC, and MS and CSK are employed by Janssen Global Services LLC, which are all subsidiaries of Johnson & Johnson. APK, ECH, XLX, SS, PA, BZ, KS, SDC, MS, and CSK also own Johnson & Johnson stock or stock options.
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