Apremilast for Discoid Lupus Erythematosus: Results of a Phase 2, Open-Label, Single-Arm, Pilot Study

October 2012 | Volume 11 | Issue 10 | Original Article | 1224 | Copyright © October 2012


Aieska De Souza MD,a Bruce E. Strober MD PhD,a Joseph F. Merola MD,a Stephen Oliver MD,a and Andrew G. Franks, Jr. MD FACPa,b

aNew York University School of Medicine, The Ronald O. Perelman Department of Dermatology bNew York University School of Medicine, Department of Medicine (Rheumatology)

Abstract
Background: Discoid lupus erythematosus (DLE) is a chronic inflammatory disorder mediated by Th1 cells. Apremilast is a novel oral PDE4 enzyme inhibitor capable of blocking leukocyte production of IL-12, IL-23, TNF-a, INF-γ with subsequent suppression of Th1 and Th17-mediated immune responses, and proven clinical efficacy for psoriasis as well as rheumatoid and psoriatic arthritis.
Observations: Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) showed a significant (P<0.05) decrease after 85 days of treatment with apremilast 20 mg twice daily in 8 patients with active discoid lupus. The adverse events related to the drug were mild and transient.
Conclusions: This is the first open label study to use apremilast as a treatment modality for discoid lupus. Our observations indicate that apremilast may constitute a safe and effective therapeutic option for DLE.

J Drugs Dermatol. 2012;11(10):1224-1226.

INTRODUCTION

Discoid lupus erythematosus (DLE) is a chronic inflammatory disorder mediated by Th (helper)-1 cells.1 Apremilast blocks the degradation of cyclic adenosine monophosphate (cAMP) via inhibition of the phosphodiesterase (PDE) 4 enzyme, and inhibition of leukocyte production of interleukin (IL)-12, IL-23, tumor necrosis factor (TNF)-α, interferon (INF)-γ.2-5 In vivo, PDE4 inhibitors have demonstrated efficacy in treating rheumatoid arthritis in animal models4 and psoriasis and psoriatic arthritis in humans.5

Report of a Case

Patients with the clinical and histopathologic diagnosis of discoid lupus, without systemic manifestations or significant co-morbidities were eligible for the study. The patients received apremilast 20 mg twice daily for 85 days, no other concomitant therapy for DLE was allowed. Study visits occurred every 14 days, during which the outcomes for clinical, immunological and safety parameters were evaluated. The CLE Disease Area and Severity Index (CLASI) was used to access the disease activity and damage at baseline (day zero), days 29, 57, and 85.6
The efficacy outcome was measured by the change in the CLASI scores6 between baseline and day 85. Results were analyzed using non-parametric statistical methods due to the small sample size. A modified intent-to-treat (MITT) analysis was performed for all patients using the Mann-Whitney test. The MITT also included data for 4 patients who dropped off the study inserted at the corresponding time points (last observation carried forward [LOCF]). In addition, a separate treated analysis of the 4 patients who completed the study was performed using the nonparametric repeated measures ANOVA (Friedman test). The values were considered statistically significant if P<0.05. Compliance was defined as intake of 80% or more of the study drug. The NYU Institutional Review Board approved the study. All patients provided written informed consent prior to enrollment in the study.

RESULTS

Demographics (Table 1)

Eight patients (7 females, 1 male) with mean age of 46 years (range: 23 to 66 years of age) were enrolled in the study. The average disease duration was 17 years (range: 3 to 52 years) at the screening visit, and the majority (75%) of subjects had failed to respond to topical corticosteroids and antimalarial medications used as either monotherapy or in combination with systemic corticosteroids. Out of 8 patients, 4 completed the study. Two patients discontinued because of disease progression and two because of adverse events. Subjects 1 and 9 were noncompliant.

Efficacy (Figures 1A, 1B)

The CLASI activity scores (Figure 1A): The MITT analysis showed a significant (P=0.01) decrease of the median scores at day 85, however it was not significant at day 57. The treated analysis also showed a marked reduction (P=0.03) in CLE activity in all 4 patients who complete the full course (85 days) of treatment. Scalp lesions completely regressed with treatment in two patients (#8, #11).
The CLASI damage scores (Figure 1B): Both the MITT and the treated analysis showed statistically significant reduction in the damage scores: P=0.004 and P=0.01, respectively, at day 85.
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