In February of 2020 (Vol 82, No. 6, pp1445–1486), the Journal of the American Academy of Dermatology published the joint Joint American Academy of Dermatology–National Psoriasis Foundation Guidelines of care for the management of psoriasis with systemic nonbiologic therapies. These guidelines are based on the foremost data and suggestions by experts in the field. The guidelines include information of the safety and efficacy of the most commonly used systemic nonbiologic medications for treatment of psoriasis, we as well provide treatment recommendations utilizing these treatment options. Here, we provide a summary of these guidelines. Readers are encouraged to visit https://www.jaad.org/article/S0190-9622(20)30284-X/fulltext to access the complete guidelines.
Methotrexate. Approved by the United States Food and Drug Administration (FDA) in 1972, methotrexate is indicated for moderate-to-severe psoriasis. It has been shown to inhibit dihydrofolate reductase and delay growth of skin cells that cause scaling. Referenced clinical studies have demonstrated methotrexate’s success in achieving clearance of psoriasis, independently and in conjunction with other therapeutic options (e.g., phototherapy). In addition to reviewing pertinent clinical data and evidence-based benefits, the guidelines provide user-friendly tables providing supporting information on methotrexate therapy, including absolute and relative contraindications, risk factors for related hepatotoxicity, strength recommendations, medications that increase the risk of toxicity, and baseline and ongoing treatment monitoring.
Apremalist. Apremalist, a phosphodiesterase Type 4 (PDE-4) inhibitor, received FDA approval in 2014. During clinical trials, anti-inflammatory and immunosuppressing properties of apremalist were observed when used continuously in patients with psoriasis and/or psoriatic arthritis. It is recommended that adverse effects (e.g., gastrointestinal [GI] problems) and pre-existing conditions (e.g., renal impairment) be carefully monitored in patients undergoing treatment with apremalist, with dosing adjusted accordingly. The guidelines indicate that a variety of patients can be treated with apremalist, even when taking other systemic agents for unrelated medical conditions. Supporting statements for these recommendations are provided in the guidelines.
Cyclosporine. Cyclosporine was FDA-approved in 1997. In referenced clinical studies, this treatment demonstrated at least 90-percent clearance in the majority of the participants. The guidelines recommend an initial dose of 2.5 to 3.0mg/kg twice a day for four weeks before slowly increasing dosage to 0.5mg/kg. For more severe cases, it is recommended that patients begin with 5mg/kg and gradually lower the dose as they show signs of improvement. However, the guidelines highlight that dosage of cyclosporine should be based on clinical judgement and the individual needs of each patient. Due to the risks of severe adverse effects (e.g., nephrotoxicity, hypertension), long-term use of cyclosporine is not recommended. Conversely, because it is a rapid-acting medication, cyclosporine is recommended for short-term treatment, such as during acute flares, erythroderma, or when transitioning to another long-term therapeutic option. The guidelines provide strength of recommendations, level of evidence, and extensive supporting statements regarding this therapy.
Acitretin. Acetretin is a second-generation oral retinoid derived from vitamin A and received FDA approval for treatment of psoriasis in 1997. This medication has shown less efficacy as a monotherapy for psoriasis when compared to other monotherapies discussed in this summary; however, its ability to regulate keratinization and proliferation of the epidermis make it particularly useful in the treatment of hyperkeratotic palmoplantar psoriasis. Acitretin is a potent teratogen; thus, it should not be used in women of childbearing potential. Information regarding the safety profile, strength recommendations, supporting statements, treatment monitoring, and level of evidence for acitretin is provided in the guidelines.
Tofacitinib. Tofacitinib, a janus kinase (JAK)1 inhibitor, has consistently demonstrated tolerability and effectiveness in numerous clinical trials for the treatment of psoriasis, most notably the Oral Treatment Psoriasis Trial (OPT); however, it has yet to receive FDA approval for the treatment of psoriasis.
Fumaric acid esters (fumarates). Like tofacitinib, fumarates have not yet received FDA approval for the treatment of psoriasis; however, they are commonly used in Europe for the treatment of moderate-to-severe psoriasis, and have been approved in the US for the treatment of psoriatic arthritis. Analyses of available data indicate their effectiveness in achieving improvements in PASI scores over placebo. GI disturbance is the common adverse effect associated with fumerates, affecting as many as two-thirds of study participants. A low initial dose that is gradually increased might mitigate this adverse effect.
Other therapies. Other therapies that aren’t broadly utilized in the treatment of psoriasis, but “still have a place in the management of various other autoimmune conditions” are reviewed, including hydroxyurea, mycophenolate mofetil, azathioprine, leflunomide, tacrolimus, and thioguanine.
*For more information on these guideline updates, please visit https://www.jaad.org/article/S0190-9622(20)30284-X/fulltext