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

RMD Open. 2020 Feb;6(1):e001149. doi: 10.1136/rmdopen-2019-001149.


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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Arthritis, Psoriatic / complications
  • Arthritis, Psoriatic / 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
  • Tumor Necrosis Factor Inhibitors / therapeutic use*
  • Ustekinumab / administration & dosage
  • Ustekinumab / therapeutic use*


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

Associated data

  • ClinicalTrials.gov/NCT01009086
  • ClinicalTrials.gov/NCT01077362