Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis

Abstract

Background: The 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).

Methods: Following 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.

Results: A 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.

Conclusions: Apremilast maintained clinical benefit and a favorable safety profile for up to 5 years among patients with PsA.

Trial registration: ClinicalTrials.gov NCT01172938 , NCT01212757 , NCT01212770.

Keywords: Apremilast; Drug safety; Psoriatic arthritis; Treatment efficacy.

Conflict of interest statement

Ethics approval and consent to participate

The institutional review boards from each participating medical center approved the study protocol for each of the three studies. All patients provided written informed consent before any study-related procedures were conducted.

Consent for publication

Not applicable.

Competing interests

AK has received grant/research support from Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, and UCB. DDG has received grant/research support from and served as a consultant for AbbVie, Amgen, BMS, Celgene Corporation, Gilead, Janssen, Novartis, Pfizer, and UCB. CJE has received grant/research support from and served as a consultant for AbbVie, BMS, Celgene Corporation, Janssen, Pfizer, Roche, Samsung, Sanofi, and UCB. GS has received grant/research support from and served as a consultant for Abbott, Celgene Corporation, Roche, and UCB. BG, ND, LT, and MP are employees of Celgene Corporation. PJM has received grant/research support from and served as a consultant for Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Genentech, Janssen, Novartis, Pfizer, and UCB, and has served on speakers bureaus for Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, and UCB.

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Figures

Fig. 1

ACR responses in PsA patients receiving apremilast 30 mg up to 260 weeks. Data as observed. The analysis includes all patient data, including the placebo-controlled phase, regardless of when the patients started taking apremilast (baseline, week 16, or week 24). The proportions of psoriatic arthritis (PsA) patients achieving ACR20, ACR50, or ACR70 responses at study visits up to week 260 are shown. Error bars represent 95% confidence interval (CI). n represents the number of patients with data available at that time point

Fig. 2

SJC/TJC improvements in PsA patients receiving apremilast 30 mg up to 260 weeks. Data as observed. The analysis includes all patient data, including the placebo-controlled phase, regardless of when the patients started taking apremilast (baseline, week 16, or week 24). The mean percentage changes in swollen joint count (SJC) and tender joint count (TJC) for psoriatic arthritis (PsA) patients at study visits up to week 260 are shown. Error bars represent 95% confidence interval (CI). n represents the number of patients with data available at that time point

Fig. 3

Enthesitis/dactylitis improvements in PsA patients receiving apremilast 30 mg up to 260 weeks. Data as observed. The analysis includes all patient data, including the placebo-controlled phase, regardless of when the patients started taking apremilast (baseline, week 16, or week 24). The proportions of patients achieving a Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) of 0 (> 0 indicating enthesitis) or a dactylitis count of 0 at study visits up to week 260 are shown. Error bars represent 95% confidence interval (CI). n represents the number of patients with either MASES ≥ 1 or dactylitis count ≥ 1 at baseline and data available at that time point

Fig. 4

Improvements in physical function among PsA patients receiving apremilast 30 mg up to 260 weeks. Data as observed. The analysis includes all patient data, including the placebo-controlled phase, regardless of when the patients started taking apremilast (baseline, week 16, or week 24). The proportions of patients achieving a Health Assessment Questionnaire-Disability Index (HAQ-DI) minimal clinically important difference (MCID) of ≥ 0.35 at study visits up to week 260 are shown. n represents the number of patients with data available at that time point