Effects of ustekinumab on spondylitis-associated endpoints in TNFi-naïve active psoriatic arthritis patients with physician-reported spondylitis: pooled results from two phase 3, randomised, controlled trials

Philip S Helliwell, Dafna D Gladman, Soumya D Chakravarty, Shelly Kafka, Chetan S Karyekar, Yin You, Kim Campbell, Kristen Sweet, Arthur Kavanaugh, Lianne S Gensler, Philip S Helliwell, Dafna D Gladman, Soumya D Chakravarty, Shelly Kafka, Chetan S Karyekar, Yin You, Kim Campbell, Kristen Sweet, Arthur Kavanaugh, Lianne S Gensler

Abstract

Background: The interleukin-12/23p40-subunit-inhibitor ustekinumab significantly improved spondylitis-related symptoms through Week 24 in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (PA-PRS) in PSUMMIT-1&2. We further evaluated ustekinumab's effect on spondylitis-related endpoints in PSUMMIT-1&2 tumour necrosis factor-inhibitor (TNFi)-naïve patients with PA-PRS.

Methods: Patients with active PsA (≥5 swollen and ≥5 tender joints, C-reactive-protein ≥ 3.0 mg/L) despite conventional (PSUMMIT-1&2) and/or prior TNFi (PSUMMIT-2) therapy received subcutaneous ustekinumab 45 mg, 90 mg or placebo (Week 0, Week 4, Week 16). Changes in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) neck/back/hip pain question (#2) and modified BASDAI (mBASDAI, excluding PA) scores and Ankylosing Spondylitis Disease Activity Score (ASDAS) responses were assessed at Weeks 12 and 24.

Results: The pooled PSUMMIT-1&2, TNFi-naïve (n=747), PA-PRS (n=223) subset (158 with human-leucocyte-antigen (HLA)-B27 results) presented with moderate-to-severe spondylitis-related symptoms (mean BASDAI-neck/back/hip pain-6.51, mBASDAI-6.54, BASDAI-6.51, ASDAS-3.81). Mean Week 24 changes were larger among ustekinumab than placebo-treated patients for both neck/back/hip pain (-1.99 vs -0.18) and mBASDAI (-2.09 vs -0.59). Improvements in neck/back/hip pain and fatigue appeared numerically greater in HLA-B27+ than HLA-B27 - patients; those for other domains were generally consistent. Greater proportions of ustekinumab versus placebo-treated patients achieved ASDAS clinically important improvement at Week 24 (decrease ≥ 1.1; 49.6% vs 12.7%; nominal p<0.05).

Conclusions: Improvements in BASDAI neck/back/hip pain and mBASDAI among ustekinumab-treated, TNFi-naïve, PsA patients with PA-PRS were clinically meaningful and consistent across assessment tools. Numerically greater improvements in neck/back/hip pain in HLA-B27+ than HLA-B27 - patients, noted in the context of similar overall mBASDAI improvements between the subgroups, suggest ustekinumab may improve disease activity in TNFi-naïve PsA patients likely to exhibit axial disease.

Clinical trial registration numbers: PSUMMIT 1, NCT01009086; PSUMMIT 2, NCT01077362.

Keywords: HLA-B27; axial disease; interleukin-12/23; psoriatic arthritis; ustekinumab.

Conflict of interest statement

Competing interests: PH has received research grants and/or payments to third parties for lectures and educational material development/events (<$10 000) from AbbVie, Amgen, Celgene, Janssen, Novartis, Pfizer and UCB. DDG has received grants and/or consultancies (<$10 000) from AbbVie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB. SDC, SK and CSK are employees of Janssen Scientific Affairs/Global Services and own stock in Johnson & Johnson, of which Janssen Scientific Affairs & Global Services are wholly owned subsidiaries. YY, KC and KS are employees of Janssen Research & Development, LLC and own stock in Johnson & Johnson, of which Janssen Research & Development, LLC, is a wholly owned subsidiary. AK has received consulting fees and research support from AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer and UCB. LSG has received consulting honoraria from Eli Lilly, GlaxoSmithKline, and Novartis and research grant support from AbbVie, Amgen, Pfizer, and UCB.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Mean (SD) changes in mBASDAI score among TNFi-naïve PsA patients with PA-PRS at Week 12 and Week 24 (A) and by HLA-B27 status at Week 12 (B) and Week 24 (C). HLA-B27, human-leucocyte-antigen B27 allele; mBASDAI, modified Bath Ankylosing Spondylitis Disease Activity Index; PA-PRS, peripheral arthritis and physician-reported spondylitis; PsA, psoriatic arthritis; TNFi, tumour necrosis factor-inhibitor.

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