Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial.

Abstract

OBJECTIVE:

Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents.

METHODS:

In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients.

RESULTS:

More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change -0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change -0.13). No unexpected adverse events were observed through week 60.

CONCLUSIONS:

The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.

• Authors: Christopher Ritchlin, Proton Rahman, Arthur Kavanaugh, Iain B McInnes, Lluis Puig, Shu Li, Yuhua Wang, Yaung-Kaung Shen, Mittie K Doyle, Alan M Mendelsohn, Alice B Gottlieb, PSUMMIT 2 Study Group
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 73 Issue 6 Pg. 990-9 (Jun 2014) ISSN: 1468-2060 [Electronic] England
• PMID: 24482301 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Immunoglobulin Fab Fragments
• Immunoglobulin G
• Interleukin-12 Subunit p40
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Polyethylene Glycols
• golimumab
• Infliximab
• Ustekinumab
• Adalimumab
• Etanercept
• Certolizumab Pegol
• Methotrexate

Topics

• Adalimumab
• Adult
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antirheumatic Agents (therapeutic use)
• Arthritis, Psoriatic (drug therapy)
• Certolizumab Pegol
• Cross-Over Studies
• Double-Blind Method
• Etanercept
• Female
• Humans
• Immunoglobulin Fab Fragments (therapeutic use)
• Immunoglobulin G (therapeutic use)
• Infliximab
• Interleukin-12 Subunit p40 (antagonists & inhibitors)
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Psoriasis (drug therapy)
• Receptors, Tumor Necrosis Factor (therapeutic use)
• Severity of Illness Index
• Treatment Failure
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)
• Ustekinumab