Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial

Abstract

Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re-randomized to apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score (PASI-75; primary) and achievement of static Physician Global Assessment (sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI-75 response rates were 7.1% (placebo), 23.5% (apremilast 20; P = 0.0032 vs placebo) and 28.2% (apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (apremilast 20; P = 0.0165 vs placebo) and 29.6% (apremilast 30; P = 0.0020 vs placebo). Responses were maintained with apremilast through week 68. Most common adverse events (AEs) with placebo, apremilast 20 and apremilast 30 (0-16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure-adjusted incidence of these AEs did not increase with continued apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies.

Keywords: Psoriasis Area and Severity Index; apremilast; phosphodiesterase 4; phosphodiesterase 4 inhibitor; psoriasis.

Figure 1

Study design. ^‡Every patient was to enter a 4‐week post‐treatment observational follow‐up phase at the time the patient completed or discontinued the study. ^§Starting at week 40, all non‐responders (<PASI‐50) had the option of adding topical therapies and/or phototherapy, at the discretion of the investigator. ^¶Doses of apremilast were titrated during the first week of administration and at week 16 when placebo patients were switched to apremilast. PASI, Psoriasis Area and Severity Index; PASI‐50, ≥50% reduction from baseline in PASI score.

Figure 2

Patient disposition through week 68. ^‡An additional five patients (two placebo/apremilast 30 mg b.i.d., one apremilast 20 mg b.i.d. and two apremilast 30 mg b.i.d.) who completed week 40 were not included in “patients who completed the apremilast treatment phase at week 68” because of missing principal investigator signature on the treatment disposition case report form. These patients were discontinued from treatment.

Figure 3

Proportions of patients who achieved (a) PASI‐75 and (b) PASI‐50 and PASI‐90 at week 16. n/m = number of responders/number of patients in the mITT population; missing data were handled using LOCF methodology. *P = 0.0032 apremilast 20 mg b.i.d. versus placebo. ^‡ P = 0.0003 apremilast 30 mg b.i.d. versus placebo. ^§ P = 0.0057 apremilast 20 mg b.i.d. vs placebo. ^¶ P < 0.0001 apremilast 30 mg b.i.d. versus placebo. ^׀׀ P = 0.0556 apremilast 20 mg b.i.d. versus placebo. ^# P = 0.0016 apremilast 30 mg b.i.d. versus placebo. LOCF, last observation carried forward; mITT, modified intent‐to‐treat; PASI, Psoriasis Area and Severity Index; PASI‐50, ≥50% reduction from baseline in PASI score; PASI‐75, ≥75% reduction from baseline in PASI score; PASI‐90, ≥90% reduction from baseline in PASI score.

Figure 4

Proportions of patients who achieved (a) PASI‐75 and (b) sPGA score of 0 (clear) or 1 (minimal) in patients with sPGA score of ≥3 (moderate or greater) at baseline over 68 weeks. n = number of responders in the mITT population; missing data were handled using non‐responder imputation. NRI, non‐responder imputation; PASI, Psoriasis Area and Severity Index; PASI‐75, ≥75% reduction from baseline in PASI score; sPGA, static Physician Global Assessment.

Figure 5

(a) Mean percentage change from baseline in PASI score and (b) mean change from baseline in pruritus VAS score (mm) (b) over 68 weeks. Includes patients in the mITT population with sufficient data for evaluation at each time point, with no imputation for missing values; data are as observed. Mean (standard deviation) pruritus VAS scores (mm) at baseline were placebo, 57.1 (26.7); apremilast 20 mg b.i.d., 49.9 (26.6); and apremilast 30 mg b.i.d., 53.1 (28.6). mITT, modified intent‐to‐treat; PASI, Psoriasis Area and Severity Index; VAS, visual analog scale.