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

ABSTRACT: To 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.Patients (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.At 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.Apremilast 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.NCT01212770.

SUBMITTER: Edwards CJ

PROVIDER: S-EPMC4893110 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Edwards Christopher J CJ Blanco Francisco J FJ Crowley Jeffrey J Birbara Charles A CA Jaworski Janusz J Aelion Jacob J Stevens Randall M RM Vessey Adele A Zhan Xiaojiang X Bird Paul P

Annals of the rheumatic diseases 20160120 6

<h4>Objective</h4>To 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.<h4>Methods</h4>Patients (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 ...[more]

PMID: 26792812

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Project description:IntroductionPsoriatic arthritis (PsA) is a spondyloarthritis that occurs in up to 30% of psoriasis patients. Patients with PsA are at risk for decreased quality of life due to both joint and skin symptoms, impaired physical function and disease progression. Treatments include non-steroidal anti-inflammatory drugs, conventional systemic disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate, and biologic agents, including tumor necrosis factor-? inhibitors. The most recently introduced treatment option is apremilast, an oral phosphodiesterase 4 inhibitor.MethodsThis review provides an in-depth discussion of apremilast's mechanism of action, and evidence of its clinical efficacy and safety from the Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) phase III pivotal clinical trials (PALACE 1, 2, and 3).ResultsThese trials demonstrate that apremilast is effective for the treatment of active PsA, despite prior conventional DMARDs or biologic treatment. The primary efficacy end point, a 20% improvement from baseline in modified American College of Rheumatology response criteria at Week 16, was achieved by significantly greater proportions of patients treated with apremilast 20 mg twice daily (BID) and apremilast 30 mg BID versus placebo in PALACE 1, 2, and 3. Improvements in this and other clinical and patient-reported end points, including swollen and tender joint counts, Psoriasis Area and Severity Index score, physical function, and quality of life, were maintained, extending over 52 weeks of treatment among patients initially randomized to apremilast. Apremilast's safety profile has been acceptable, with diarrhea and nausea being the most common adverse events, with no evidence for an increased risk of infection or need for laboratory monitoring. The PALACE pivotal data indicate that apremilast presents a new option for the treatment of PsA that may be appropriate for use early in the treatment ladder. Ongoing PALACE open-label extension trials of up to 4 years will characterize the long-term clinical effects and safety of apremilast therapy.FundingCelgene Corporation, Summit, NJ, USA.

Project description:ObjectivesApremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.MethodsIn the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16.ResultsAt week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed.ConclusionsApremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated.Clinical trial registration numberNCT01172938.

Project description:BackgroundThe efficacy and safety of apremilast were assessed in patients with psoriatic arthritis (PsA) in three phase III clinical trials with similar designs (PALACE 1, 2, and 3).MethodsFollowing a 24-week, randomized (1:1:1 to apremilast 30 mg twice daily, 20 mg twice daily, or placebo), double-blind phase and a 28-week blinded active treatment phase, patients could receive apremilast in open-label extension studies for an additional 4 years. Eligible adult patients had active PsA for ≥ 6 months and three or more swollen joints and three or more tender joints despite prior treatment with disease-modifying anti-rheumatic drugs.ResultsA total of 1493 randomized patients received one or more doses of study medication (placebo: n = 496; apremilast 30 mg twice daily: n = 497; apremilast 20 mg twice daily: n = 500). In patients continuing apremilast treatment, response was sustained without new safety issues. At week 260, 67.2% of remaining patients achieved an ACR20 response, and 44.4% and 27.4% achieved ACR50 and ACR70 responses, respectively. Among patients with baseline enthesitis and dactylitis, 62.4% achieved a Maastricht Ankylosing Spondylitis Enthesitis Score of 0 and 80.9% achieved a dactylitis count of 0, respectively. In patients who had ≥ 3% baseline psoriasis body surface area involvement, 43.6% achieved ≥ 75% reduction from the baseline Psoriasis Area and Severity Index scores. The most commonly reported adverse events (AEs) were diarrhea, nausea, headache, upper respiratory tract infection, and nasopharyngitis, with most diarrhea and nausea AEs occurring within the first 2 weeks of treatment and usually resolving within 4 weeks. Reported rates of depression during the study were low (≤ 1.8%). The majority of patients maintained their weight within 5% of baseline during the study. No new safety concerns or increases in the incidence or severity of AEs were observed over the long term.ConclusionsApremilast maintained clinical benefit and a favorable safety profile for up to 5 years among patients with PsA.Trial registrationClinicalTrials.gov NCT01172938 , NCT01212757 , NCT01212770.

Dataset Information

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

Publications

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

Similar Datasets

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