Acitretin

Abstract

Recently, the biologics have emerged as a new class of drugs for systemic therapy of psoriasis with efalizumab (Raptiva[R]) being one of the most recently FDA-approved agents. We report a case of a 34-year-old Caucasian male who experienced psoriasis rebound during a 7-week lapse in treatment with subcutaneous efalizumab 0.8 mg/kg/week, which he had been using for 4 weeks up to that point. The patient then restarted efalizumab, but his psoriasis continued to worsen causing him to be admitted for Goeckerman day care. He rebounded again 4 weeks following his ultimate discontinuation of efaluzimab despite intensive therapy with the Goeckerman regimen. This case is reported to highlight the recent findings that psoriasis rebound, defined as psoriasis area and severity index (PASI) of 125% or greater or morphology change, has been associated with both the use and the discontinuation of efalizumab.

Background

Psoriasis is a disease that affects 2.6% of American people making it one of the most prevalent dermatologic diseases in the US. (1) Recently, a new class of drugs has emerged for systemic therapy of psoriasis. One of them, efalizumab, is a humanized monoclonal antibody that binds the CD11a surface molecule on T-lymphocytes, which prevents binding of LFA-1 to ICAM-1 thus preventing T-cell migration from the bloodstream to the skin. (2) Rebound of psoriasis is defined by the National Psoriasis Foundation as a psoriasis area and severity index (PASI) score of 125% or greater or a morphology change, such as to generalized pustular, or erythrodermic psoriasis, occurring within 3 months of discontinuation from any psoriasis therapy. (3) Rebound has been associated with discontinuation of efalizumab therapy in approximately 13.8% of patients from 4 pooled efalizumab clinical trials involving 1,316 patients who had been treated for a minimum of 12 and a maximum of 36 weeks. (4,5) Patients who failed to achieve a 50% reduction in PASI score were at the greatest risk of experiencing a rebound, (4) but 10% of patients who rebounded during clinical trials of efalizumab had achieved greater than a PASI 75 within 3 months. (4)

Case Report

We report a case of a 34-year-old Caucasian male with a 6-year history of psoriasis who has tried the following therapies: topical calcipotriene and halobetasol, UVB phototherapy 3 times per week for 2 months, methotrexate 2.5 mg 1 tablet per week for 5 months, etanercept 25 mg subcutaneously twice per week for 5 months and acitretin 25 mg daily for 2 months. All were discontinued due to insufficient efficacy, but the patient had no adverse reactions to any of his prior therapies. He began efalizumab 0.8 mg/kg/week at the end of February and continued for 4 weeks until the beginning of April at which time he temporarily stopped for 7 weeks due to perceived lack of efficacy and expense of the medication. The patient noticed during this time that his psoriasis worsened while off of therapy as it spread to his shoulders and upper extremities, resulting in a PASI greater than 125% as these are large areas that were not involved before beginning treatment with efalizumab. He restarted efalizumab in the end of May after 7 weeks without the drug, but the disease continued to worsen. Eventually, his psoriasis spread to cover greater than 90% of his body surface area and took on such an intense erythematous appearance that he appeared erythrodermic.

Once admitted to the UCSF Psoriasis Treatment Center in mid-July, the Goeckerman regimen was initiated while the efalizumab was discontinued. At first, the patient responded well while being treated solely with aggressive Goeckerman therapy, but approximately 4 weeks following his final dose of efalizumab the patient again rebounded with erythrodermic psoriasis over greater than 90% of his body surface area (Figure 1-3). Cyclosporine therapy was considered at that time, but the patient gave a history of heavy alcohol use, a recent 30-pound weight loss, and had inguinal lymphadenopathy on physical exam. Fine needle aspiration biopsies of the lymph nodes revealed reactive changes only. The patient was advised to have an evaluation by his primary medical provider for the weight loss, and the primary medical team determined that because his liver enzymes were elevated, the patient may use cyclosporine only if he reduce his alcohol intake. The patient agreed to reduce his alcohol consumption, and in the meantime cyclosporine was withheld while Goeckerman was continued. After 17 weeks of the Goeckerman regimen, the patient's psoriasis remitted and he was discharged from Goeckerman day care.

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Discussion

While clinical trials have shown that 13.8% of psoriasis patients experience rebound after discontinuation of efalizumab, (4,5) and a case of rebound following treatment of psoriasis with efalizumab has been documented in the literature, (6) we believe this is the first literature reported case of a patient experiencing rebound while receiving efalizumab therapy and a subsequent rebound after final discontinuation of the drug despite being treated with the Goeckerman regimen. This case is presented to highlight the possibility that, first, psoriasis may rebound during treatment with efalizumab and, further, even one of the most efficacious treatments available, such as all-day, daily traditional Goeckerman regimen, may not be adequate to prevent efalizumab rebound.

References

1. Koo J. Population-based epidemiologic study of psoriasis with emphasis on quality of life assessment. Dermatol Clin. 1996;14:485-496.

2. Cather JC, Cather JC, Menter A. Modulating T cell responses for the treatment of psoriasis: a focus on efalizumab. Expert Opin Biol Ther. 2003;3:361-370.

3. Gordon KB, Koo JY, Feldman SR, Menter A, Krueger G. Definitions of measures of effect duration for psoriasis treatments. Psoriasis Forum. 2002;8:1-5.

4. Menter A, Kardatzke D, Rundle AC, Kwon P, Garvory MR, Leonardi CL. Incidence and Prevention of Rebound Upon Efalizumab Discontinuation. Poster presented at The 10th International Psoriasis Symposium, June 10-13, 2004, Toronto, Canada.

5. Carey W, Rundle AC, Kwon P, Leonardi CL. Taper Regimens in the Management of Patients Discontinuing Efalizumab Therapy. Poster presented at The 10th International Psoriasis Symposium, June 10-13, 2004, Toronto, Canada.

6. Gaylor ML, Duvic M. Generalized pustular psoriasis following withdrawal of efaluzimab. J Drugs Dermatol. 2004;3:77-79.

Address for Correspondence

Nicholas Golda MD

University of Missouri, Columbia

Dept. of Dermatology

7106 Stanwood Drive

Columbia, MO 65203

Phone: 573-268-4969

email: goldan@health.edu

Nicholas Golda MD, (a) Shahrad M. Benham MD, (b) John Koo MD (c)

a. Keck School of Medicine of the University of Southern California, Los Angeles, CA

b. School of Medicine, Oregon Health & Sciences University, Portland, OR

c. Vice-Chair UCSF Department of Dermatology, Director UCSF Psoriasis and Phototherapy Day Treatment Center, San Francisco, CA

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