Apremilast: A Review in Psoriasis and Psoriatic Arthritis

Abstract

Apremilast (Otezla(®)) is an oral phosphodiesterase 4 inhibitor indicated for the twice-daily treatment of adults with psoriasis and psoriatic arthritis (PsA). Its use in these patient populations has been assessed in two phase III clinical trial programmes (ESTEEM and PALACE). At 16 weeks in the two ESTEEM trials, apremilast reduced the severity and extent of moderate to severe plaque psoriasis, including nail, scalp and palmoplantar manifestations, versus placebo in adults, with these benefits generally being sustained over 52 weeks of treatment. Similarly, in three PALACE trials (PALACE 1-3), apremilast improved the signs and symptoms of PsA relative to placebo at 16 weeks in adults with active disease despite treatment with conventional synthetic and/or biologic disease-modifying anti-rheumatic drugs. These PsA benefits were generally sustained for up to 104 weeks of treatment; skin involvement, enthesitis and dactylitis also improved with the drug. Apremilast was generally well tolerated, with the most common adverse events being diarrhoea and nausea in the first year of treatment (usually occurring in the first 2 weeks after the first dose and resolving within 4 weeks) and nasopharyngitis and upper respiratory tract infection with continued treatment. Although further longer-term and comparative efficacy and tolerability data would be beneficial, the current clinical data indicate that apremilast is an effective and well tolerated option for the management of psoriasis and PsA in adults.

Treatment of recalcitrant erosive oral lichen planus and desquamative gingivitis with oral apremilast

“…Apremilast is a phosphodiesterase-4 inhibitor that has been successfully used in the treatment of psoriasis and oral ulceration in Behcet's disease. 5,6 Apremilast effectively inhibits the production of TNF-alpha, IFN-gamma, IL-2, IL-5, IL-8, and IL-12, all of which contribute to the pathogenesis of OLP by activation of cytotoxic T-cells, and mediating basal keratinocytes apoptosis in OLP. 4,5,7 In a recent study, ten patients with biopsy-proven cutaneous LP received 20 mg of apremilast orally twice daily for 12 weeks with 4 weeks of treatment-free follow-up.…”

“…5,6 Apremilast effectively inhibits the production of TNF-alpha, IFN-gamma, IL-2, IL-5, IL-8, and IL-12, all of which contribute to the pathogenesis of OLP by activation of cytotoxic T-cells, and mediating basal keratinocytes apoptosis in OLP. 4,5,7 In a recent study, ten patients with biopsy-proven cutaneous LP received 20 mg of apremilast orally twice daily for 12 weeks with 4 weeks of treatment-free follow-up. Thirty percent of the patients achieved a 2-grade or more improvement in the Physician Global Assessment after 12 weeks of treatment and all patients demonstrated clinical improvement with lesions count at the end of treatment.…”

“…There were no serious adverse effects reported in large studies of apremilast when used for psoriasis and psoriatic arthritis. 5,6,9 Apremilast therefore would be an ideal systemic agent for this chronic disease given its good safety profile. Up to now cases reports of patients with oral lichen planus treated with apremilast were published, both in 2016.…”

An Update on Medical Treatment Options for Hidradenitis Suppurativa

“…It is a selective inhibitor of phosphodiesterase 4, and has been shown in vivo to inhibit the production of the pro-inflammatory cytokines (e.g., IL-2, IL-5, IL-12A, IL-13, IL-17 IL-23A, TNF-a, INF-a, and INF-c), and chemokines (e.g., CXCL9 and CXCL10) [145].…”

“…Even though these therapeutic options have been shown to be effective in psoriasis [143][144][145], no studies are available on their use in HS.…”