Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial

Abstract

Objectives: The PALACE 4 trial evaluated apremilast monotherapy in patients with active PsA who were DMARD-naive.

Methods: Eligible patients were randomized (1:1:1) to placebo, apremilast 20 mg twice a day or apremilast 30 mg twice a day. At week 16 or 24, placebo patients were rerandomized to apremilast. Double-blind apremilast treatment continued to week 52, with extension up to 4 years. The primary endpoint was the proportion of patients achieving ⩾20% improvement in ACR response criteria (ACR20) at week 16; secondary endpoints included the mean change in the HAQ Disability Index (HAQ-DI) score at week 16.

Results: A total of 527 patients with mean disease duration of 3.4 years and high disease activity were randomized and received treatment. More apremilast patients achieved ACR20 response at week 16 [placebo, 15.9%; 20 mg, 28.0% (P = 0.0062); 30 mg, 30.7% (P = 0.0010)]. The mean HAQ-DI improvements were -0.17 (20 mg; P = 0.0008) and -0.21 (30 mg; P < 0.0001) vs 0.03 (placebo). Both apremilast doses showed significant ACR50 responses vs placebo at week 16 and improvements in secondary efficacy measures (swollen/tender joint counts) and psoriasis assessments, with sustained improvements through week 52. Common adverse events (AEs) over 52 weeks were diarrhoea, nausea, headache and upper respiratory tract infection; most events were mild or moderate. Serious AEs and AEs leading to discontinuation were comparable between groups. Laboratory abnormalities were infrequent and transient.

Conclusions: In DMARD-naive patients, apremilast monotherapy improved PsA signs/symptoms over 52 weeks and was generally well tolerated.

Trial registration: ClinicalTrials.gov (https://ichgcp.net/clinical-trials-registry/NCT01307423" title="See in ClinicalTrials.gov">NCT01307423.

Keywords: apremilast; monotherapy; phase III clinical trial; phosphodiesterase 4 inhibitor; psoriatic arthritis.

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig. 1

ACR20 response rates and HAQ-DI scores at week 16 (modified intent-to-treat population) (A) Proportion of patients achieving ACR20 response at week 16 (NRI, non-responder imputation): modified intent-to-treat population. *P = 0.0062, **P = 0.0010 vs placebo. (B) Mean change from baseline in HAQ-DI at week 16 (last-observation-carried-forward methodology): modified intent-to-treat population. ***P = 0.0008, ****P < 0.0001 vs placebo.

Fig. 2

ACR20, HAQ-DI and PASI-50/PASI-75 response rates over 52 weeks (data as observed) (A) ACR20, (B) HAQ-DI and (C) PASI-50/PASI-75. Based on patients randomized to apremilast; the placebo/apremilast 20 mg BID and placebo/apremilast 30 mg BID groups include patients who were randomized to placebo at baseline and rerandomized to apremilast 20 mg BID and apremilast 30 mg BID, respectively, at week 16 or 24; the apremilast 20 mg BID and apremilast 30 mg BID groups include patients randomized to the respective regimen at baseline. Patients with baseline psoriasis involvement ≥3% of BSA were included.