Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials

Abstract

ObjectiveEvaluate ustekinumab, an anti-interleukin (IL)-12 and IL-23 antibody, effects on radiographic progression in psoriatic arthritis (PsA).MethodsWe conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3, randomised, controlled trials. Patients had active PsA despite prior conventional and/or biologic disease-modifying antirheumatic drugs (≥5/66 swollen, ≥5/68 tender joints, C-reactive protein ≥3.0 mg/L, documented plaque psoriasis). Patients (PSUMMIT-1, n=615; PSUMMIT-2, n=312) were randomised to ustekinumab 45 mg, 90 mg, or placebo, at weeks (wk) 0, 4 and every (q) 12 wks. At wk 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape. All other placebo patients received ustekinumab 45 mg at wk 24 and wk 28, then q 12 wks. Radiographs of hands/feet at wks 0/24/52 were assessed using PsA-modified van der Heijde-Sharp (vdH-S) scores; combined PSUMMIT-1 and PSUMMIT-2 changes in total vdH-S scores from wk 0 to wk 24 comprised the prespecified primary radiographic analysis. Treatment effects were assessed using analysis of variance on van der Waerden normal scores (factors=treatment, baseline methotrexate usage, and study).ResultsIntegrated data analysis results indicated that ustekinumab-treated patients (regardless of dose) demonstrated significantly less radiographic progression at wk 24 than did placebo recipients (wk 0–24 total vdH-S score mean changes: 0.4-combined/individual ustekinumab dose groups, 1.0-placebo; all p<0.02). From wk 24 to wk 52, inhibition of radiographic progression was maintained for ustekinumab-treated patients, and progression was substantially reduced among initial placebo recipients who started ustekinumab at wk 16 or wk 24 (wk 24 – wk 52, total vdH-S score mean change: 0.08).ConclusionsUstekinumab 45 and 90 mg treatments significantly inhibited radiographic progression of joint damage in patients with active PsA.

Brief Report: Secukinumab Provides Significant and Sustained Inhibition of Joint Structural Damage in a Phase III Study of Active Psoriatic Arthritis

“…However, failure of anti‐TNF treatment, loss of efficacy, and intolerance in some patients highlight the unmet need for new therapies with an alternative mechanism of action 12. The radiographic findings from this study are consistent with those from other trials of TNF and IL‐12/23 inhibitors involving anti‐TNF–naive populations 13, 14, 15, 16, 17 and suggest that IL‐17A may offer an additional therapeutic option for patients with PsA.…”

Secukinumab: A New Treatment Option for Psoriatic Arthritis

“…Some of these agents, such as the phosphodiesterase 4 (PDE4) inhibitor apremilast [20] and the interleukin (IL)-12/23 inhibitor ustekinumab [21], have demonstrated efficacy in clinical trials and are approved for use in PsA in the majority of developed countries. Nevertheless, because of inadequate efficacy, intolerance, or safety issues new treatments with alternative modes of action continue to be sought.…”

Inflammatory osteolysis: a conspiracy against bone

“…However, RANKL inhibition, per se, has no intrinsic anti-inflammatory properties and therefore must be accompanied by anti-inflammatory agents in these disorders (172). All current cytokine inhibitors approved for the treatment of inflammatory diseases, which include compounds specifically targeting IL-1, IL-6R, IL-17, IL-12/23, and in particular TNF-α, limit osteolysis (173)(174)(175). The efficacy of TNF-α inhibitors appears to reflect combined anti-inflammatory properties and direct suppression of bone-resorbing osteoclasts.…”