Newer biologic agents for treating moderate-to-severe plaque psoriasis do not carry the risk of end-organ toxicities found with older, conventional systemic agents and can be considered for first-line use in some cases, according to new psoriasis treatment guidelines from the National Psoriasis Foundation.
On the other hand, conventional drugs such as methotrexate and cyclosporine often are effective, but have significant toxicities, including liver problems with methotrexate and kidney problems with cyclosporine, according to guideline authors Sylvia Hsu, MD, of Baylor College of Medicine in Houston, and colleagues.
Because the biologics don't have significant end-organ toxicities, "no clinical reason supports reserving the biologicals for second-line use," the guideline authors stated in the January Archives of Dermatology, noting that these drugs do, however, have some safety issues of their own. "The biological agents used to treat psoriasis represent significant recent additions to the dermatologist's toolkit."
The guidelines, which summarize the benefits and drawbacks of systemic agents currently in use for
psoriasis, are an update of earlier recommendations developed in Canada.
In comparing the benefits of the conventional oral agents, Hsu and colleagues noted that methotrexate is less effective in clearing plaques than cyclosporine, which can reduce disease severity by 75%. However, methotrexate can be used for years, while cyclosporine should be used intermittently for periods no longer than 12 weeks. Methotrexate also is teratogenic, so contraceptive use is necessary for both men and women.
A third oral agent is the retinoid acitretin (Soriatane), which also is teratogenic and is limited in efficacy, so it often is used as part of a combination regimen with topical calcipotriene (Dovonex) or phototherapy.
Among the biologic agents, three tumor necrosis factor (TNF) inhibitors all have demonstrated high levels of efficacy in clearing plaque psoriasis.
However, these immunosuppressant agents have been linked with serious infections, autoimmunity, and malignancies such as lymphoma during long-term use for other conditions such as rheumatoid arthritis, so careful monitoring is needed.
One TNF inhibitor, etanercept (Enbrel), typically is given in subcutaneous doses of 50 mg twice each week and then once weekly after three months, with 75% improvement in about half of patients. For many patients, however, better responses are seen if the higher dose is continued, and no additional safety concerns have arisen with the dose increase.
Another TNF inhibitor, "infliximab [Remicade] offers rapid and thorough suppression of
psoriasis," with almost half of patients having a 90% reduction in
symptoms in less than three months, the guidelines stated. This agent is given as an intravenous infusion of 5 mg/kg at weeks zero, two, and six, and every eight weeks thereafter.
Adalimumab (Humira), a third TNF inhibitor, is administered in a loading dose of 80 mg, followed by subcutaneous doses of 40 mg every other week. In a clinical trial comparing adalimumab with methotrexate, the TNF inhibitor was associated with higher rates of 75%, 90%, and 100% improvements in skin scores as well as with fewer adverse events.
Other biologic options include ustekinumab (Stelara) and alefacept (Amevive).
Ustekinumab is a monoclonal antibody that targets interleukins 12 and 23. In clinical studies, sustained 75% improvement was seen in more than two-thirds of patients, with rapid responses occurring as early as the second week of
treatment.
Alefacept is a fusion protein that blocks pathogenic T lymphocytes, and while no major safety concerns have emerged, CD4 T-cell depletion can occur and patients must be monitored. Like cyclosporine, alefacept should be given intermittently in 12-week courses up to twice per year.
A 50% to 75% improvement in skin scores has been seen in about one-quarter of patients given alefacept, and while few patients experience complete clearance, the safety profile appears excellent, the guideline authors observed.