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Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor.

ABSTRACT: Apremilast, 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.In 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.At 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.Apremilast 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.NCT01172938.

SUBMITTER: Kavanaugh A

PROVIDER: S-EPMC4033106 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor.

Kavanaugh Arthur A Mease Philip J PJ Gomez-Reino Juan J JJ Adebajo Adewale O AO Wollenhaupt Jürgen J Gladman Dafna D DD Lespessailles Eric E Hall Stephen S Hochfeld Marla M Hu ChiaChi C Hough Douglas D Stevens Randall M RM Schett Georg G

Annals of the rheumatic diseases 20140304 6

<h4>Objectives</h4>Apremilast, 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.<h4>Methods</h4>In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a d ...[more]

PMID: 24595547

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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:Apremilast, a specific inhibitor of phosphodiesterase 4, modulates pro-inflammatory and anti-inflammatory cytokine production.Apremilast's effect on patient-reported outcomes (PROs) in patients with moderate to severe psoriasis was evaluated in a phase IIb randomized, controlled trial (NCT00773734).In this 16-week, placebo-controlled study, 352 patients with moderate to severe plaque psoriasis received placebo or apremilast (10, 20, or 30 mg BID). PROs included Dermatology Life Quality Index (DLQI), pruritus visual analog scale (VAS), and Short-Form Health Survey (SF-36) to assess health-related quality of life (HRQOL). Changes from baseline and patients reporting improvements ?minimum clinically important differences (MCID) were analyzed. Correlations between changes across various PRO instruments were explored.Baseline DLQI (>10 points) and SF-36 MCS and domain scores indicated impairments in HRQOL. At 16 weeks, greater improvements from baseline in DLQI scores were reported with apremilast 20 (-5.9) and 30 mg BID (-4.4) compared with placebo (1.9; P?0.005 for both), and a greater proportion of patients reported improvements ?MCID (20 mg BID, 49.4%, 30 mg BID, 44.3%) versus placebo (25.0%; P<0.04). Greater improvements from baseline in pruritus VAS scores were reported with apremilast 20 (-35.5%) and 30 mg BID (-43.7%) versus placebo (-6.1%; P?0.005). Significant and clinically meaningful improvements in SF-36 mental component summary scores (P?0.008) and Bodily Pain, Mental Health, and Role-Emotional domains were reported with all apremilast doses (P<0.05), and Social Functioning with 20 and 30 mg BID (P<0.05) and Physical Functioning with 20 mg BID (P<0.03). Correlations between SF-36 scores and DLQI were moderate (r>0.30 and ?0.60) and low between SF-36 and pruritus VAS (r?0.30), indicating they measure different aspects of the disease.Apremilast treatment resulted in improved HRQOL, including DLQI and pruritus VAS over 16 weeks of treatment, in patients with moderate to severe psoriasis.

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Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor.

Publications

Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor.

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