D05: Antipsoriatics
D05 holds drugs used mainly against psoriasis, split into antipsoriatics for topical use (D05A) and for systemic use (D05B) [1]. Psoriasis drugs outside D05 include ustekinumab (L04AC05), which is classified under L04A [1,2]. The disease itself is covered in the psoriasis primer.
How do antipsoriatics work?
Vitamin D analogues include calcipotriol (D05AX02), which stimulated the final maturation (terminal differentiation) and inhibited proliferation of cultured human outer-layer skin cells (epidermal keratinocytes) [3].
Retinoids include acitretin (D05BB02), taken by mouth, and tazarotene (D05AX05), applied to the skin. Esterases rapidly hydrolyze tazarotene to its active metabolite, tazarotenic acid [4].
Psoralens, such as methoxsalen (D05BA02), are inactive unless they are combined with long-wave ultraviolet light (UVA), a treatment called photochemotherapy or PUVA [5].
Efficacy
In a systematic review of 37 trials of calcipotriol, efficacy was compared as the percentage change in the Psoriasis Area and Severity Index (PASI) and as the rate of marked improvement or better on patients’ and investigators’ overall assessments [6]. How psoriasis trials use PASI and the physician’s global assessment (PGA), and how the two scores are modeled, is covered in the psoriasis primer.
For PUVA, sensitivity has been measured as the minimal phototoxic dose of UVA. Patients with a high methoxsalen clearance and a low Cmax usually show less sensitivity to PUVA than low-clearance patients, and frequently a less favorable clinical response [5].
Safety
Etretinate (D05BB01) and its active metabolite acitretin are known causes of birth defects (teratogens) [7]. In a study of 37 women of childbearing age exposed to acitretin, etretinate was detectable in subcutaneous fat in 83% of those still taking acitretin. Acitretin or etretinate could still be found in fat up to 29 months after the women had stopped acitretin, and an undetectable plasma etretinate concentration was a poor predictor of its absence from fat [8].
In the same systematic review, calcipotriol caused more skin irritation than potent topical corticosteroids, although the irritation rarely led to withdrawal of treatment [6].
The systemic bioavailability of topical tazarotene is about 1% on healthy skin, and rises to 5% or less at steady state in psoriasis. Its low systemic exposure gives topical tazarotene a low potential for systemic adverse effects [4].