moderate severity. Improvement of psoriasis is generally noted following 2 weeks of therapy, with continued improvement for up to 8 weeks of treatment. However, fewer than 10% of patients demonstrate total clearing while on calcipotriene as single-agent therapy. Adverse effects include burning, itching, and mild irritation, with dryness and erythema of the treatment area. Care should be taken to avoid facial contact, which may cause ocular irritation. A once-daily two-compound ointment (Taclonex) or foam (Enstilar) containing calcipotriene and betamethasone dipropionate are available. This combination is more effective than its individual ingredients and is well tolerated, with a safety profile similar to betamethasone dipropionate.
Calcitriol (Vectical) contains 1,25-dihydroxycholecalciferol, the hormonally active form of vitamin D3. Calcitriol 3 mcg/g ointment is similar in efficacy to calcipotriene 0.005% ointment for the treatment of plaque-type psoriasis on the body and is better tolerated in intertriginous and sensitive areas of the skin. Clinical studies show comparable safety data regarding adverse cutaneous and systemic reactions between topical calcitriol and calcipotriene ointment.
Biologic agents useful in treating adult patients with moderate to severe chronic plaque psoriasis include the TNF-α inhibitors adalimumab, etanercept, and infliximab, and the cytokine inhibitors ixekizumab, secukinumab, and ustekinumab (Table 61–2). The pharmacology of these agents is discussed in Chapters 36 and 55.
Apremilast (Otezla) is an oral phosphodiesterase 4 (PDE4) inhibitor that is effective in treating moderate to severe plaque psoriasis. Selective inhibition of PDE4 specific for cyclic adenosine monophosphate (cAMP) results in increased intracellular cAMP levels. The specific mechanism by which apremilast exerts its therapeutic effect in psoriasis is not known. Initial dosage titration from day 1 to day 5, intended to reduce the gastrointestinal symptoms associated with starting therapy, is shown in Table 61–3. Following the 5-day titration, a maintenance dose of 30 mg twice daily is started on day 6.
Treatment with apremilast is associated with an increased incidence of depression. Patients should have their weight monitored regularly due to possible weight loss associated with therapy. Use of cytochrome P450 enzyme inducers (see chapter 4) may result in a loss of efficacy and is not recommended. Apremilast is generally well tolerated with mild gastrointestinal complaints occurring early in the course of treatment that resolve with time.
Fumaric acid esters (Fumaderm) are licensed in Germany for the oral treatment of psoriasis. They are considered homeopathic treatment in the USA and are not approved or regulated by the FDA for the treatment of psoriasis. Dimethyl fumarate (Tecfidera) has recently been approved by the FDA for treatment of multiple sclerosis. The mechanism of action of dimethyl fumarate in psoriasis may be due to immunomodulatory effects on lymphocytes and keratinocytes, resulting in a shift away from a psoriatic cytokine profile. Note that four cases of progressive multifocal leukoencephalopathy have been reported in psoriasis patients treated with fumaric acid esters.