Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: Results of a double‐blind, randomized, placebo‐controlled trial

Mease, Philip; Gladman, Dafna D.; Ritchlin, Christopher T.; Ruderman, Eric; Steinfeld, Serge; Choy, Ernest; Sharp, John J.; Ory, Peter P.A.; Perdok, Renee R.J.; Weinberg, Mark

doi:10.1002/art.21306

Cited by 837 publications

(715 citation statements)

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“…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.…”

Section: Discussionsupporting

confidence: 76%

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

Heijde

Landewé

Mease

et al. 2016

Arthritis & Rheumatology

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ObjectiveTo assess whether secukinumab treatment in patients with active psoriatic arthritis (PsA) is associated with sustained inhibition of radiographic progression.MethodsIn this phase III, double‐blind, placebo‐controlled study, 606 patients with PsA were randomized to receive intravenous (IV) secukinumab at a dose of 10 mg/kg (weeks 0, 2, 4) followed by subcutaneous secukinumab at a dose of 150 mg or 75 mg (the IV→150 mg and IV→75 mg groups, respectively) or placebo. Patients were stratified according to prior anti–tumor necrosis factor (anti‐TNF) exposure (71% were anti‐TNF naive). At week 16, placebo‐treated patients who had at least a 20% reduction in the tender and swollen joint counts (responders) continued to receive placebo until week 24; nonresponders were re‐randomized to receive secukinumab at a dose of 150 mg or 75 mg. The modified total Sharp/van der Heijde score (SHS) was determined at baseline, week 16 or 24, and week 52.ResultsIn the overall population, radiographic progression was inhibited through 52 weeks; efficacy was demonstrated for both erosion and joint space narrowing scores and in patients who switched from placebo to secukinumab at week 24. Subgroup analyses showed that secukinumab reduced radiographic progression at week 24, regardless of previous anti‐TNF treatment. Among anti‐TNF–naive patients, the mean changes from baseline to week 24 in the modified total SHS were 0.05 in the pooled secukinumab group and 0.57 in the placebo group; among patients with an inadequate response or intolerance to anti‐TNF treatment, the mean changes were 0.16 and 0.58, respectively. Anti‐TNF–naive patients showed negligible progression through week 52. Inhibition of structural damage was observed through week 52 irrespective of concomitant methotrexate use. A high proportion of patients receiving secukinumab showed no progression (change in SHS of ≤ 0.5) from baseline to week 24 (82.3% of the IV→150 mg group and 92.3% of the IV→75 mg group) and from week 24 to week 52 (85.7% of the IV→150 mg group and 85.8% of the IV→75 mg group).ConclusionSecukinumab inhibited radiographic progression over 52 weeks of treatment in patients with active PsA.

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Section: Discussionsupporting

confidence: 76%

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

Heijde

Landewé

Mease

et al. 2016

Arthritis & Rheumatology

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“…Anti-tumor necrosis factor ␣ (anti-TNF␣) agents improve the arthritic and psoriatic manifestations of PsA (2)(3)(4). Golimumab is a new human monoclonal antibody against TNF␣ that binds with high affinity and specificity to soluble and transmembrane TNF␣ and has a median terminal half-life of ϳ2 weeks (5).…”

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confidence: 99%

Golimumab, a new human tumor necrosis factor α antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty‐four–week efficacy and safety results of a randomized, placebo‐controlled study

Kavanaugh¹,

McInnes²,

Mease³

et al. 2009

Arthritis & Rheumatism

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489

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Objective. To assess the efficacy and safety of golimumab in patients with active psoriatic arthritis (PsA). Methods. Adult patients withPsA who had at least 3 swollen and 3 tender joints and active psoriasis were randomly assigned to receive subcutaneous injections of placebo (n ‫؍‬ 113), golimumab 50 mg (n ‫؍‬ 146), or golimumab 100 mg (n ‫؍‬ 146) every 4 weeks through week 20. Efficacy assessments through week 24 included the American College of Rheumatology 20% improvement criteria (ACR20), the Psoriasis Area and Severity Index (PASI) in patients in whom at least 3% of the body surface area was affected by psoriasis at baseline, the Short Form 36 Health Survey (SF-36), the disability index of the Health Assessment Questionnaire (HAQ), the Nail Psoriasis Severity Index (NAPSI), the physician's global assessment of psoriatic nail disease, and enthesitis (using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score [MASES] index).Results. At week 14, 48% of all patients receiving golimumab, 51% of patients receiving golimumab 50 mg, and 45% of patients receiving golimumab 100 mg achieved an ACR20 response (the primary end point), compared with 9% of patients receiving placebo (P < 0.001 for all comparisons). Among the 74% of patients in whom at least 3% of the body surface area was affected by psoriasis at baseline, 40% of those in the golimumab 50 mg group and 58% of those in the golimumab 100 mg group had at least 75% improvement in the PASI at week 14 (major secondary end point), compared with 3% of placebo-treated patients (P < 0.001 for both doses). Significant improvement was observed for other major secondary end points (the HAQ and the SF-36), the NAPSI, the physician's global assessment of psoriatric nail disease, and the PsAClinicalTrials.gov identifier: NCT00265096.

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“…Although 12 weeks has been an adequate length of time to assess the efficacy of other biologic agents in terms of improvements in both the skin and the joints 10, 11, 12, 13, 14, it remains a limitation in terms of reaching conclusions with regard to safety. Another limitation is that although an active comparator arm targeting TNF inhibition alone (adalimumab) was included for comparison to ABT‐122, the study had no active comparator with an agent that targeted IL‐17A inhibition alone.…”

Section: Discussionmentioning

confidence: 99%

“…Levels of TNF and IL‐17A–producing CD8+ T cells are elevated in the synovial fluid of patients with PsA 4, 9. Inhibition of either TNF or IL‐17A alone has demonstrated efficacy in improving joint inflammation, features of skin disease, and quality of life in patients with PsA 10, 11, 12, 13, 14, 15, 16, suggesting that TNF and IL‐17A may both contribute to the pathophysiology of PsA. An unanswered question has been whether, assuming that the contributions of TNF and IL‐17A are at least partly independent of one another, dual neutralization of TNF and IL‐17A may provide the opportunity to achieve better control of inflammation in patients with PsA compared to neutralization of either target alone.…”

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confidence: 99%

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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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Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: Results of a double‐blind, randomized, placebo‐controlled trial

Cited by 837 publications

References 38 publications

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

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

Golimumab, a new human tumor necrosis factor α antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty‐four–week efficacy and safety results of a randomized, placebo‐controlled study

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

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