Apremilast with Add-On Calcipotriene/Betamethasone Dipropionate for Treating Moderate to Severe Plaque Psoriasis

December 2020 | Volume 19 | Issue 12 | Original Article | 1149 | Copyright © December 2020


Published online November 5, 2020

Jerry Bagel MD MS, Elise Nelson LPN CCRC, Cheryl Riley BS CCRC, Alexa Hetzel MS PA-C

Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ

Abstract
Background: About 20% of patients taking apremilast alone obtain PASI 75 by week 8. This single-center, pilot study aimed to determine whether add-on topical therapy with calcipotriene/betamethasone dipropionate (C/BD) could improve responses of partial apremilast responders by week 12.
Methods: Adults (≥18 years of age) with moderate to severe plaque psoriasis (baseline PGA ≥3, BSA affected ≥10%, PASI ≥12) took oral apremilast (30 mg twice daily) for 8 weeks. Patients who achieved between PASI 25–74 at week 8 used add-on, daily topical C/BD (.005%/.064%) foam up to week 12; those with <PASI 25 at week 8 were discontinued.
Results: Of 50 patients enrolled, 26 achieved PASI 25−74 and 8 PASI 75 at week 8. At week 12, 29 achieved PASI 75, and 24 at week 16. Of the week-8 partial responders, 21/26 achieved PASI 75 at week 12 on combination therapy and 15 maintained PASI 75 through week 16 on apremilast alone (4 did not maintain; 2 lost to follow up). In partial responders, mean PGA and BSA affected improved by 30% and 33% on apremilast, respectively, and by 67% and 86% at week 12 on the combination therapy, respectively. The most commonly reported adverse events (AEs; >5% occurrence) were headache (14%), diarrhea (10%), and nausea (8%); majority were mild. No related serious AEs occurred.
Conclusion: We show that most week-8 partial apremilast responders can achieve PASI 75 at week 12 with combination C/BD topical therapy, and maintain PASI 75 through week 16 with apremilast monotherapy.

J Drugs Dermatol. 2020;19(12):1149-1155. doi:10.36849/JDD.2020.5435

INTRODUCTION

Psoriasis is a chronic, immune-mediated skin disease that affects approximately 3% of the population in the US.1,2 Moderate to severe psoriasis is associated with a number of medical comorbidities, including but not limited to psoriatic arthritis, cardiovascular disease, metabolic syndrome, and depression.3,4 Psoriasis also impair patients’ quality of life,4,5 with an impact similar to those by other serious chronic diseases, such as cancer or cardiovascular diseases.5

Among different subtypes of psoriasis, plaque psoriasis is the most common form, characterized by a raised silvery scale with underlying erythema, itching, and discomfort. Although there is no cure for the disease, a variety of treatment options including topical, phototherapy, oral, and biologic therapies are available to manage clinical symptoms, with topical medication usually used to treat mild psoriasis and the latter three to treat moderate to severe psoriasis.6 However, not all patients can achieve adequate responses (75% reduction in psoriasis area severity index [PASI] score6) to monotherapies. Combination therapy with different modalities has been ultilized.7-11 Therapies with different mechanisms of action could generate a synergistic effect, thus enhancing the treatment effect without the need of increasing dosages and subsequently minimizing adverse events.9,11,12

Despite their established efficacy in treating psoriasis,13 many patients are reluctant to receive biologic agents due to safety and tolerability concerns, anxiety or fear of injection, inconvenience in administration, or loss of effectiveness over time.14 Patients may be hesitant to use biologics by the reported adverse effects such as tuberculosis, inflammatory bowel disease, serious infections, or depression with specific biologics.15 Non-biological systemic medications remain widely used with comparatively increased availability and ease of administration.16 Apremilast is an oral systemic agent that inhibits phosphodiesterase 4.17 Two phase 3, randomized, controlled studies showed that apremilast effectively controlled moderate to severe plaque psoriasis with acceptable tolerability and improved quality of life.18-20 However, the proportions of patients who achieved PASI 75 response at week 16 were 33% (ESTEEM 1)18 and 29% (ESTEEM 2)19 in the studies, showing the vast majority of the patients did not have sufficient improvement with apremilast monotherapy.

Topical therapies combined with systemic medications are frequently used to treat psoriasis patients with BSA >10%.8 Adjunctive topical therapy has been shown to improve the efficacy of biologics, systemic agents, and phototherapy in treating moderate to severe psoriasis without causing