Erythrodermic Psoriasis Drug Review Calls for Guideline Update, Biologic Meds Included

Erythrodermic Psoriasis Drug Review Calls for Guideline Update, Biologic Meds Included

Researchers at the University of California, Los Angeles recently provided a research review concerning treatment of erythrodermic psoriasis, a rare but severe version of common plaque psoriasis that effects at least 75% of the body.

The review, “Erythrodermic psoriasis: pathophysiology and current treatment perspectives,” published in the journal Psoriasis: Targets and Therapy, suggests that current treatment guidelines for the condition should be updated and should include new biological drugs that show better results and fewer side effects.

The U.S. National Psoriasis Foundation  published treatment guidelines in 2010, detailing how patients with erythrodermic psoriasis should be managed once the condition is stabilized. At the time, the guidelines supported cyclosporine or infliximab as first-line treatment in acute and unstable patients, reserving acitretin and methotrexate for more stable cases.

Since then, new information and new drugs have appeared. Topical therapy, applied directly to the skin, is not a common approach today, although steroids, vitamin D analogs, and light therapy has been used as an add-on treatment, or for patients who have severe side effects from oral drugs.

Etretinate, and even more so its active metabolite acitretin, both in a group of drugs called retinoids, are considered good options for patients in stable condition.  Several studies show the drugs effective in clearing lesions. Etretinate has also been combined with drugs such as cyclosporine and infliximab.

Methotrexate — the first treatment option for patients with plaque psoriasis who do not improve with topical treatment — is also used in stable erythrodermic psoriasis. Several studies support the drug’s effectivity in the more severe condition, showing rates of good or complete remission in 60-80% of the time. Methotrexate has been combined with other drugs, including infliximab, etretinate, reaching excellent results in combination with cyclosporine or etanercept.

The immunosuppressant cyclosporin, blocking the cytokine IL-2 — one of the first steps in the activation of an immune response — is often used in unstable cases of erythrodermic psoriasis because it acts quickly. Complete remission after treatment with cyclosporin was reported in 67% of patients in a study of 33 patients. As an immunosuppressant, it is joined by Mycophenolate mofetil, showing evidence in small studies and a clinical trial to be effective.

Biological drugs, which some consider revolutionary in treating psoriasis, act in more specific ways than immunosuppressant drugs. The TNF-α blocker etanercept was among the first biological drugs approved for psoriasis. Like many biological drugs, the response to etanercept is slow. Eighteen erythrodermic psoriasis patients have been treated with 67% achievement.

Adalimumab and infliximab also target TNF-α. While adalimumab is similar to etanercept because patients have to wait 12 weeks to before noticing potential reduction in symptoms, infliximab can ease symptoms after 48 hours and has been tried by the largest number of patients, with 55 % of 55 patients reaching a good response.

Recently, case reports have indicated that infliximab can lose effectiveness over time, and researchers believe that the body might develop antibodies against the drug, blocking its action. Studies suggest that the development of antinuclear and anti-double-stranded DNA antibodies might flag a future treatment failure, but larger studies are needed to confirm the finding.

The last contribution to TNF-α blocking drugs, golimumab, has only been tested in one patient with erythrodermic psoriasis, in which the treatment was successful.

Another approach to psoriasis treatment is blocking the cytokines IL-12 and IL-23 with the drug ustekinumab. Studies including 40 patients, showed 80% good response. Symptons began to fade among almost half the group within four weeks. The treatment has also been effective in several patients with erythrodermic psoriasis who were not helped by TNF-blocking drugs.

Ixekizumab, acting on the cytokine IL-17 involved in the inflammatory mechanisms of psoriasis, was recently tested in a Phase 3 trial in patients with erythrodermic psoriasis with all patients showing good results after 12 weeks.

While a small population of people with erythrodermic psoriasis limits possibilities for gathering large amounts of evidence for drug effectiveness, the review authors suggest that there is enough evidence of the efficacy of ustekinumab and other biologics, particularly TNF-α blockers, to be included in updated treatment guidelines.

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Magdalena is a writer with a passion for bridging the gap between the people performing research, and those who want or need to understand it. She writes about medical science and drug discovery. She holds an MS in Pharmaceutical Bioscience and a PhD — spanning the fields of psychiatry, immunology, and neuropharmacology — from Karolinska Institutet in Sweden.

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