scholarly journals Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3)

2016 ◽  
Vol 75 (6) ◽  
pp. 1065-1073 ◽  
Author(s):  
Christopher J Edwards ◽  
Francisco J Blanco ◽  
Jeffrey Crowley ◽  
Charles A Birbara ◽  
Janusz Jaworski ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Rescue Therapy ◽  
Controlled Trial ◽  
Health Assessment ◽  
Severity Index ◽  
Index Score ◽  
Phase Iii ◽  
Upper Respiratory Tract ◽  
Skin Involvement ◽  
Tender Joint

ObjectiveTo evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.MethodsPatients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed over 52 weeks.ResultsAt week 16, significantly more patients receiving apremilast 20 mg twice daily (28%) and 30 mg twice daily (41%) achieved 20% improvement in American College of Rheumatology response criteria versus placebo (18%; p=0.0295 and p<0.0001, respectively), and mean decrease in the Health Assessment Questionnaire-Disability Index score was significantly greater with apremilast 30 mg twice daily (−0.20) versus placebo (−0.07; p=0.0073). In patients with baseline psoriasis body surface area involvement ≥3%, significantly more apremilast 30 mg twice daily patients achieved 50% reduction from baseline Psoriasis Area and Severity Index score (41%) versus placebo (24%; p=0.0098) at week 16. At week 52, observed improvements in these measures demonstrated sustained response with continued apremilast treatment. Most adverse events were mild to moderate in severity; the most common were diarrhoea, nausea, headache and upper respiratory tract infection.ConclusionsApremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks. Apremilast was generally well tolerated and demonstrated an acceptable safety profile.Trial registration numberNCT01212770.

A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial

2016 ◽  
Vol 43 (9) ◽  
pp. 1724-1734 ◽  
Author(s):  
Maurizio Cutolo ◽  
Gary E. Myerson ◽  
Roy M. Fleischmann ◽  
Frédéric Lioté ◽  
Federico Díaz-González ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Physical Function ◽  
Controlled Trial ◽  
Signs And Symptoms ◽  
Adenosine Monophosphate ◽  
Phase Iii ◽  
Tender Joint Count ◽  
Upper Respiratory Tract ◽  
Tender Joint ◽  
Link Type

Objective.Apremilast, an oral phosphodiesterase 4 inhibitor, downregulates intracellular inflammatory mediator synthesis by elevating cyclic adenosine monophosphate levels. The PALACE 2 trial evaluated apremilast efficacy and safety in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs and/or biologic therapy.Methods.Eligible patients were randomized (1:1:1) to placebo, apremilast 20 mg BID, or apremilast 30 mg BID. At Week 16, patients with swollen and tender joint count improvement < 20% entered early escape, with placebo patients rerandomized (1:1) to apremilast 20 mg BID or 30 mg BID while apremilast patients continued on their initial apremilast dose. At Week 24, patients remaining on placebo were rerandomized to apremilast 20 mg BID or 30 mg BID. The primary endpoint was the proportion of patients achieving > 20% improvement in American College of Rheumatology response criteria (ACR20) at Week 16.Results.In the intent-to-treat population (N = 484), ACR20 at Week 16 was achieved by more patients receiving apremilast 20 mg BID [37.4% (p = 0.0002)] and 30 mg BID [32.1% (p = 0.0060)] versus placebo (18.9%). Clinically meaningful improvements in signs and symptoms of PsA, physical function, and psoriasis were observed with apremilast through Week 52. The most common adverse events were diarrhea, nausea, headache, and upper respiratory tract infection. Diarrhea and nausea generally occurred early and usually resolved spontaneously with continued treatment. Laboratory abnormalities were infrequent and transient.Conclusion.Apremilast demonstrated clinical improvements in PsA for up to 52 weeks, including signs and symptoms, physical function, and psoriasis. No new safety signals were observed. ClinicalTrials.gov identifier: NCT01212757.

scholarly journals Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE)

2018 ◽  
Vol 77 (5) ◽  
pp. 690-698 ◽  
Author(s):  
Peter Nash ◽  
Kamal Ohson ◽  
Jessica Walsh ◽  
Nikolay Delev ◽  
Dianne Nguyen ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Safety Profile ◽  
Controlled Trial ◽  
Health Assessment ◽  
Tender Joint ◽  
American College Of Rheumatology ◽  
Das 28 ◽  
Registration Number ◽  
Randomised Controlled

ObjectiveEvaluate apremilast efficacy across various psoriatic arthritis (PsA) manifestations beginning at week 2 in biological-naïve patients with PsA.MethodsPatients were randomised (1:1) to apremilast 30 mg twice daily or placebo. At week 16, patients whose swollen and tender joint counts had not improved by ≥10% were eligible for early escape. At week 24, all patients received apremilast through week 52.ResultsAmong 219 randomised patients (apremilast: n=110; placebo: n=109), a significantly greater American College of Rheumatology 20 response at week 16 (primary outcome) was observed with apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109) (P=0.025). Improvements in other efficacy outcomes, including 28-joint count Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and morning stiffness severity, were observed with apremilast at week 2. At week 16, apremilast significantly reduced PsA disease activity versus placebo, with changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index (P=0.001). Improvements were maintained with continued treatment through week 52. Over 52 weeks, apremilast’s safety profile was consistent with prior phase 3 studies in psoriasis and PsA. During weeks 0–24, the incidence of protocol-defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse event rates were 2.8% (apremilast) and 4.6% (placebo).ConclusionsIn biological-naïve patients with PsA, onset of effect with apremilast was observed at week 2 and continued through week 52. The safety profile was consistent with previous reports.Trial registration numberNCT01925768; Results.

scholarly journals Effect of Secukinumab on the Different GRAPPA-OMERACT Core Domains in Psoriatic Arthritis: A Pooled Analysis of 2049 Patients

2019 ◽  
Vol 47 (6) ◽  
pp. 854-864 ◽  
Author(s):  
Ana-Maria Orbai ◽  
Iain B. McInnes ◽  
Laura C. Coates ◽  
M. Elaine Husni ◽  
Dafna D. Gladman ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Complete Resolution ◽  
Severity Index ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Tender Joint ◽  
Related Quality ◽  
Health Related ◽  
Future 2

Objective.To compare the efficacy of secukinumab with that of placebo across the updated Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and Outcome Measures in Rheumatology (GRAPPA-OMERACT) individual psoriatic arthritis (PsA) core domains using pooled data from 4 phase III PsA studies and 1 phase III ankylosing spondylitis (AS) study.Methods.Data were pooled from 2049 patients with PsA participating in 4 on-label phase III PsA studies (FUTURE 2–5), and the efficacy of each GRAPPA-OMERACT PsA core domain (musculoskeletal disease activity, skin disease activity, pain, patient’s global assessment, physical function, health-related quality of life, fatigue, and systemic inflammation) was assessed using multiple measures and definitions specific to each domain. The MEASURE 2 study, a phase III clinical trial in patients with AS, was used to assess improvement in spine symptoms at Week 16.Results.Treatment with secukinumab demonstrated robust and consistent efficacy across all GRAPPA-OMERACT PsA core domains, with secukinumab 300 mg showing the greatest response rates across most PsA core domains compared with placebo at Week 16. Notably, among patients treated with secukinumab 300 mg, 34.3% and 19.5% achieved complete resolution of swollen and tender joint counts, respectively; 53.2% and 61.5% achieved complete resolution of enthesitis and dactylitis, respectively; and 33.2% achieved 100% improvement in Psoriasis Area and Severity Index (all p < 0.05 vs placebo); similar improvements were shown for all other core domains.Conclusion.This analysis suggests that secukinumab can benefit people with PsA across the clinical phenotypic spectrum commonly encountered in this disease.

scholarly journals Application and Modifications of Minimal Disease Activity Measures for Patients with Psoriatic Arthritis Treated with Adalimumab: Subanalyses of ADEPT

2013 ◽  
Vol 40 (5) ◽  
pp. 647-652 ◽  
Author(s):  
Philip J. Mease ◽  
Michele Heckaman ◽  
Sonja Kary ◽  
Hartmut Kupper
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Global Assessment ◽  
Health Assessment ◽  
Severity Index ◽  
Tender Joint Count ◽  
Physician Global Assessment ◽  
Minimal Disease Activity ◽  
Tender Joint ◽  
Minimal Disease

Objective.This posthoc analysis evaluated the percentage of patients with psoriatic arthritis (PsA) who achieved minimal disease activity (MDA) and compared the results with a modified MDA substituting the physician global assessment (PGA) for the Psoriasis Activity and Severity Index (PASI) using data from the ADalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT; NCT00646386).Methods.Patients with active PsA were randomized to receive adalimumab 40 mg or placebo every other week for 24 weeks. MDA was defined as achieving ≥ 5 of the following criteria: tender joint count ≤ 1; swollen joint count ≤ 1; PASI ≤ 1 or body surface area ≤ 3%; patient pain score ≤ 15 [1–100 mm visual analog scale (VAS)]; patient global assessment (PGA) of disease activity ≤ 20 (1–100 mm VAS); Health Assessment Questionnaire ≤ 0.5; and tender entheseal points ≤ 1 (only heels assessed). For modification of the MDA, PASI ≤ 1 was substituted with PGA “Clear” as MDAPGA1 and PGA “Clear” or “Almost clear” as MDAPGA2.Results.Sixty-seven patients were treated with adalimumab and 69 with placebo. At Week 24, MDA, MDAPGA1, and MDAPGA2 were achieved by 39%, 37%, and 39%, respectively, of patients treated with adalimumab versus 7%, 5%, and 8% of patients on placebo (p < 0.001). Kappa coefficients indicated good agreement between PASI and PGA at Week 24.Conclusion.ADEPT results indicated that significantly more patients treated with adalimumab achieved MDA by Week 24 compared with placebo. Modification of the MDA by replacing PASI ≤ 1 with PGA assessments did not alter the results, which may improve feasibility of practical use of the index.

scholarly journals Efficacy and Safety of Ixekizumab in Patients with Active Psoriatic Arthritis: 52-week Results from a Phase III Study (SPIRIT-P1)

2017 ◽  
Vol 45 (3) ◽  
pp. 367-377 ◽  
Author(s):  
Désirée van der Heijde ◽  
Dafna D. Gladman ◽  
Mitsumasa Kishimoto ◽  
Masato Okada ◽  
Suchitrita S. Rathmann ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Injection Site ◽  
Injection Site Reaction ◽  
Response Rates ◽  
Severity Index ◽  
Phase Iii ◽  
Upper Respiratory Tract ◽  
Efficacy And Safety ◽  
Phase Iii Study ◽  
Extension Period

Objective.To evaluate the efficacy and safety of ixekizumab (IXE), an interleukin 17A antagonist, in patients with psoriatic arthritis (PsA) after 52 weeks in a phase III study.Methods.Patients were initially randomly assigned to IXE 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after a 160-mg starting dose, placebo (PBO), or adalimumab (ADA) 40 mg Q2W. At Week 24 (Week 16 for inadequate responders), ADA (8-week washout before starting IXE) and PBO patients were rerandomized to IXEQ2W or IXEQ4W. Six treatment groups were evaluated in the extension period (weeks 24–52): IXEQ2W/IXEQ2W, IXEQ4W/IXEQ4W, ADA/IXEQ2W, ADA/IXEQ4W, PBO/IXEQ2W, and PBO/IXEQ4W. The extension period population (EPP) included patients who received ≥ 1 dose of study medication during the extension period.Results.There were 381/417 (91.4%) patients who entered the extension period. In the IXEQ4W/IXEQ4W and IXEQ2W/IXEQ2W groups (EPP), respectively, American College of Rheumatology (ACR)20 (69.1% and 68.8%), ACR50 (54.6% and 53.1%), and ACR70 (39.2% and 39.6%) response rates were sustained at Week 52. Patients rerandomized to IXE also demonstrated efficacy measured by ACR response rates at Week 52. A similar pattern was observed for Psoriasis Area and Severity Index outcomes. Radiographic progression in all 6 groups was minimal. The most frequently reported treatment-emergent adverse events (≥ 4%) were nasopharyngitis, injection site reaction, injection site erythema, upper respiratory tract infection, and back pain. No deaths were reported, and serious adverse event frequency was 0–4% with IXE.Conclusion.During the extension period, IXEQ4W or IXEQ2W treatment demonstrated sustained efficacy in key PsA domains with a safety profile consistent with other studies investigating IXE. Clinical trial number: NCT01695239; EudraCT 2011-002326-49.

scholarly journals Longterm (52-week) Results of a Phase III Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis

2015 ◽  
Vol 42 (3) ◽  
pp. 479-488 ◽  
Author(s):  
Arthur Kavanaugh ◽  
Philip J. Mease ◽  
Juan J. Gomez-Reino ◽  
Adewale O. Adebajo ◽  
Jürgen Wollenhaupt ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Controlled Trial ◽  
Signs And Symptoms ◽  
Phase Iii ◽  
Tender Joint ◽  
Clinical Trial Registration ◽  
Acr20 Response ◽  
Phosphodiesterase 4 ◽  
American College Of Rheumatology

Objective.To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, over 52 weeks in patients with active psoriatic arthritis (PsA) despite prior treatment.Methods.Patients were randomized to placebo (n = 168), apremilast 20 mg BID (n = 168), or apremilast 30 mg BID (n = 168). Patients whose swollen and tender joint counts had not improved by ≥ 20% at Week 16 were considered nonresponders and were required to be re-randomized (1:1) to apremilast 20 mg BID or 30 mg BID if they were initially randomized to placebo, or continued their initial treatment of apremilast dose. At Week 24, all remaining patients treated with placebo were re-randomized to apremilast 20 mg BID or 30 mg BID.Results.An American College of Rheumatology 20 (ACR20) response at Week 16 was attained by significantly more patients receiving apremilast 20 mg BID (30.4%, p = 0.0166) or 30 mg BID (38.1%, p = 0.0001) than placebo (19.0%). Among patients receiving apremilast continuously for 52 weeks (n = 254), ACR20 response at Week 52 was observed in 63.0% (75/119, 20 mg BID) and 54.6% (71/130, 30 mg BID) of patients. Response was also maintained across secondary outcomes, including measures of PsA signs and symptoms, skin psoriasis severity, and physical function. The nature, incidence, and severity of adverse events were comparable over the 24-week and 52-week periods. The most common adverse events, diarrhea and nausea, generally occurred early and were self-limited.Conclusion.Continuous apremilast treatment resulted in sustained improvements in PsA for up to 52 weeks. Apremilast had an acceptable safety profile and was generally well tolerated. Clinical trial registration: NCT01172938.

scholarly journals Poor prognostic factors in predicting abatacept response in a phase III randomized controlled trial in psoriatic arthritis

2020 ◽  
Vol 40 (7) ◽  
pp. 1021-1028 ◽  
Author(s):  
Philip J. Mease ◽  
Iain B. McInnes ◽  
Vibeke Strand ◽  
Oliver FitzGerald ◽  
Harris A. Ahmad ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Prognostic Factors ◽  
Psoriatic Arthritis ◽  
Controlled Trial ◽  
Phase Iii ◽  
Randomized Controlled

scholarly journals Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions

2009 ◽  
Vol 69 (2) ◽  
pp. 394-399 ◽  
Author(s):  
F Van den Bosch ◽  
B Manger ◽  
P Goupille ◽  
N McHugh ◽  
E Rødevand ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Clinical Response ◽  
Health Assessment ◽  
Severity Index ◽  
Skin Lesions ◽  
Physician Global Assessment ◽  
Good Clinical Response ◽  
Open Label ◽  
Response Predictors ◽  
Male Sex

Objectives:To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions.Methods:Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: ⩾50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a ⩾3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a ⩾50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%).Results:Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of “clear/almost clear” increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria.Conclusions:Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.

scholarly journals Comparison of Etanercept Monotherapy and Combination Therapy with Methotrexate in Psoriatic Arthritis: Results from 2 Clinical Trials

2016 ◽  
Vol 43 (6) ◽  
pp. 1063-1067 ◽  
Author(s):  
Bernard Combe ◽  
Frank Behrens ◽  
Neil McHugh ◽  
Fiona Brock ◽  
Urs Kerkmann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Combination Therapy ◽  
Health Assessment ◽  
Severity Index ◽  
Joint Disease ◽  
Reactive Protein ◽  
American College Of Rheumatology ◽  
Psa Response ◽  
Questionnaire Disability

Objective.To evaluate the clinical/functional outcomes associated with etanercept (ETN) monotherapy versus combination therapy in psoriatic arthritis (PsA).Methods.Data from patients with PsA who received ETN alone (n = 322) or combined with methotrexate (MTX; n = 152) for 24 weeks in 2 placebo-controlled clinical trials were summarized across studies.Results.Similar proportions of patients in the monotherapy and combination therapy groups achieved the PsA Response Criteria (80% and 83%) and the American College of Rheumatology improvements of 20% (ACR20; both 70%); numerically higher proportions receiving monotherapy achieved ACR50 (55% vs 48%) and ACR70 (35% vs 27%). Little between-group difference was observed in the 28-joint Disease Activity Score with C-reactive protein, the Psoriasis Area and Severity Index, and the Health Assessment Questionnaire–Disability Index improvement.Conclusion.ETN with and without MTX provided similar benefits in active PsA.

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