Current Concepts in Psoriatic Arthritis: Pathogenesis and Management

Vlam, Kurt de; Gottlieb, Alice B.; Mease, Philip J.

doi:10.2340/00015555-1833

Cited by 69 publications

(56 citation statements)

References 114 publications

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“…2 PsA can be progressive and destructive, resulting in physical deformities, impaired function, decreased quality of life and increased mortality 34 The cytokine interleukin (IL)-17A promotes joint inflammation and damage by triggering the activation and trafficking of immune cells, inducing proinflammatory cytokines and chemokines, acting as a chemoattractant to neutrophils and monocytes, and stimulating release of matrix metalloproteases and receptor activator of nuclear factor kappa-B ligand, which contribute to cartilage and bone destruction, respectively 5.…”

Section: Introductionmentioning

confidence: 99%

Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1

et al. 2016

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ObjectiveTo assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA).MethodsPatients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24.ResultsSignificantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7–66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05).ConclusionsIn biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo.Trial registration numberNCT01695239; EudraCT2011-002326-49; Results.

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Section: Introductionmentioning

confidence: 99%

Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1

et al. 2016

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“…Psoriatic arthritis (PsA) is a chronic immune‐mediated inflammatory arthritis that is associated with psoriasis 1. Multiple pathways and mediators contribute to the pathogenesis of PsA, including tumor necrosis factor (TNF) 2, 3, 4 and interleukin‐17A (IL‐17A) 1, 5, 6, 7, 8.…”

mentioning

confidence: 99%

“…psoriasis (1). Multiple pathways and mediators contribute to the pathogenesis of PsA, including tumor necrosis factor (TNF) (2)(3)(4) and interleukin-17A (IL-17A) (1,(5)(6)(7)(8). Levels of TNF and IL-17A-producing CD8+ T cells are elevated in the synovial fluid of patients with PsA (4,9).…”

mentioning

confidence: 99%

Phase II Study of ABT‐122, a Tumor Necrosis Factor– and Interleukin‐17A–Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate

Mease

Genovese

Weinblatt

et al. 2018

Arthritis & Rheumatology

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ObjectiveTo investigate the safety and efficacy of ABT‐122, a tumor necrosis factor (TNF)– and interleukin‐17A (IL‐17A)–targeted dual variable domain immunoglobulin, in patients with active psoriatic arthritis (PsA) who have experienced an inadequate response to methotrexate.MethodsPatients (n = 240) were randomized to receive ABT‐122 (120 or 240 mg every week), adalimumab (40 mg every other week), or placebo in a 12‐week double‐blind, parallel‐group study. The primary efficacy end point was the proportion of patients achieving ≥20% improvement in disease activity according to the American College of Rheumatology response criteria (ACR20) at week 12. Secondary and exploratory 12‐week end points included 50% improvement (ACR50) and 70% improvement (ACR70) response rates, and proportion of patients meeting the Psoriasis Area and Severity Index (PASI) response criteria for ≥75% (PASI75) and ≥90% (PASI90) improvement in skin scores among those with ≥3% of their body surface area affected by psoriasis.ResultsIn both ABT‐122 dose groups, ACR20 response rates at week 12 (64.8–75.3%) were superior to that in patients receiving placebo (25.0%) (P < 0.001) but similar to that in patients receiving adalimumab (68.1%). ACR50 and ACR70 response rates were also superior in both ABT‐122 dose groups (36.6–53.4% and 22.5–31.5%, respectively) compared to the placebo group (12.5% and 4.2%, respectively) (P < 0.05). Among eligible patients in the placebo, adalimumab, ABT‐122 120 mg every week, and ABT‐122 240 mg every week treatment groups, PASI75 responses were achieved in 27.3%, 57.6%, 74.4%, and 77.6% of patients, respectively, whereas PASI90 responses were achieved in 18.2%, 45.5%, 48.8%, and 46.9% of patients, respectively. Frequencies of treatment‐emergent adverse events, including infections, were similar across all treatment groups, causing no discontinuations. No serious infections or systemic hypersensitivity reactions were reported with ABT‐122.ConclusionDual neutralization of TNF and IL‐17A with ABT‐122 had efficacy and safety that was similar to, and not broadly differentiated from, that of adalimumab over a 12‐week treatment course in patients with PsA.

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“…155 The 2008 American Journal of Cardiology Editor's Consensus on Psoriasis and Coronary Artery Disease recommended that all patients with moderate-to-severe psoriasis be informed of a potential increased risk for coronary artery disease, 156 and these guidelines may be followed for all patients with PsA as well. The panel also recommended ascertaining the family history of the patient, assessing the patient's blood pressure, and performing screening lipid profiles and fasting blood glucose testing.…”

Section: Complicationsmentioning

confidence: 99%