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.

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.

• Authors: 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
• Journal: RMD open (RMD Open) Vol. 6 Issue 1 (02 2020) ISSN: 2056-5933 [Electronic] England
• PMID: 32209721 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 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.

Chemical References

• Antibodies, Monoclonal, Humanized
• HLA-B27 Antigen
• Placebos
• Tumor Necrosis Factor Inhibitors
• Interleukin-12
• Ustekinumab

Topics

• Adult
• Antibodies, Monoclonal, Humanized (administration & dosage, therapeutic use)
• Arthritis, Psoriatic (complications, drug therapy)
• Case-Control Studies
• Female
• HLA-B27 Antigen (drug effects)
• Humans
• Injections, Subcutaneous
• Interleukin-12 (antagonists & inhibitors)
• Male
• Middle Aged
• Physicians (statistics & numerical data)
• Placebos (administration & dosage)
• Spondylitis (drug therapy)
• Tumor Necrosis Factor Inhibitors (administration & dosage, therapeutic use)
• Ustekinumab (administration & dosage, therapeutic use)