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Leflunomide in Psoriasis and Psoriatic Arthritis: A Preliminary Study

Leflunomide in Psoriasis and Psoriatic Arthritis: A Preliminary Study Psoriasis and its associated arthritis is an immunologic disease that is characterized by chronic inflammatory dermatosis and a seronegative arthropathy that resembles rheumatoid arthritis.1,2 Disease-modifying antirheumatic drugs, such as methotrexate, cyclosporine, and sulfasalazine, are variably effective in treating both rheumatoid and psoriatic arthritis (PA).2 Recently, leflunomide, a newer disease-modifying antirheumatic drug that has shown promising results in rheumatoid arthritis, has been used in patients with PA, with some benefit.1-3 Its active metabolite, teriflunomide (A77-1726), inhibits de novo pyrimidine synthesis through selective inhibition of a dihydro-orotase dehydrogenase.1 Actively proliferating cells, such as activated T and B lymphocytes, which require increased pyrimidine pools, undergo cell cycle arrest and inhibition of clonal expansion in the presence of leflunomide. The anti-inflammatory and immunomodulatory effects of leflunomide in PA and psoriasis may also be due to inhibition of nuclear factor κB–dependent gene transcription, tumor necrosis factor–induced activation of nuclear factor κB, and expression of cell adhesion molecules and protein kinases.3 We studied the efficacy of leflunomide in the treatment of patients with psoriasis with or without associated PA. The study included 10 patients (7 men and 3 women; age range, 23-67 years) with mild to moderate psoriasis (average duration of disease, 4-27 years). Five patients had only psoriasis vulgaris, involving 30% to 50% of their body surface area; 3 patients had psoriasis vulgaris with PA; and 2 patients had generalized pustular psoriasis. The drugs that the patients had used before leflunomide therapy included methotrexate, psoralen–UV-A, sulfasalazine, and cyclosporine with or without nonsteroidal anti-inflammatory drugs. The results of pretreatment evaluation, including a complete blood cell count, renal and hepatic functions tests, urinalysis, and chest x-ray films, were normal in all 10 patients. The pretreatment psoriasis area and severity index scores were recorded and compared every 2 weeks to assess the response to treatment. Joint disease was also evaluated with respect to pain intensity, swelling, discomfort, and deformity. All patients received a loading dose of leflunomide (100 mg/d for 3 days), followed by 20 mg/d for 6 to 8 months. No clinically remarkable improvement was observed in cutaneous lesions of either the plaque or the pustular type. A mild to moderate improvement in pain intensity, joint swelling, and physical activity was observed in patients with associated arthropathy. Leflunomide primarily exerts its activity through T lymphocytes, which may suppress proinflammatory T-helper cell, cytokine-mediated, epidermal cell proliferation of psoriasis. An upregulation of anti-inflammatory factors, such as interleukins 1 and 10 receptor proteins, may also produce an antipsoriatic effect.2-4 Leflunomide also inhibits epidermal cell proliferation through induction of negative cell cycle inhibitor p 53. Although improvement in joint erosions has been radiologically observed in a patient with PA, the efficacy of leflunomide therapy for psoriasis vulgaris has not been clinically proved.5 Our preliminary observations in this open trial of a small group of patients suggest that leflunomide fails to show clinical efficacy in psoriasis vulgaris despite its potential use as an anti-inflammatory and immunomodulatory agent in PA. However, although leflunomide therapy may be beneficial for patients with PA, further evaluation is needed. The authors have no relevant financial interest in this article. Correspondence: Dr Thami, Department of Dermatology and Venereology, Government Medical College and Hospital, Sector-32B, Chandigarh 160030, India (thamigp@yahoo.com). References 1. Reich KHummel KMBeckmann IMossner RNeumann C Treatment of severe psoriasis and psoriatic arthritis with leflunomide Br J Dermatol. 2002;146335- 336PubMedGoogle ScholarCrossref 2. Sanders SHarisdangkul V Leflunomide for the treatment of rheumatoid arthritis and autoimmunity Am J Med Sci. 2002;323190- 193PubMedGoogle ScholarCrossref 3. Pipitone NKingsley GHManzo AScott DLPitzalis C Current concepts and new developments in the treatment of psoriatic arthritis Rheumatology. 2003;421138- 1148PubMedGoogle ScholarCrossref 4. Brockbank JGladman D Diagnosis and management of psoriatic arthritis Drugs. 2002;622447- 2457PubMedGoogle ScholarCrossref 5. Cuchacovich MSoto L Leflunomide decreases joint erosions and induces reparative changes in a patient with psoriatic arthritis Ann Rheum Dis. 2002;61942- 943PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Leflunomide in Psoriasis and Psoriatic Arthritis: A Preliminary Study

Archives of Dermatology , Volume 140 (10) – Oct 1, 2004

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Publisher
American Medical Association
Copyright
Copyright © 2004 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.140.10.1288
Publisher site
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Abstract

Psoriasis and its associated arthritis is an immunologic disease that is characterized by chronic inflammatory dermatosis and a seronegative arthropathy that resembles rheumatoid arthritis.1,2 Disease-modifying antirheumatic drugs, such as methotrexate, cyclosporine, and sulfasalazine, are variably effective in treating both rheumatoid and psoriatic arthritis (PA).2 Recently, leflunomide, a newer disease-modifying antirheumatic drug that has shown promising results in rheumatoid arthritis, has been used in patients with PA, with some benefit.1-3 Its active metabolite, teriflunomide (A77-1726), inhibits de novo pyrimidine synthesis through selective inhibition of a dihydro-orotase dehydrogenase.1 Actively proliferating cells, such as activated T and B lymphocytes, which require increased pyrimidine pools, undergo cell cycle arrest and inhibition of clonal expansion in the presence of leflunomide. The anti-inflammatory and immunomodulatory effects of leflunomide in PA and psoriasis may also be due to inhibition of nuclear factor κB–dependent gene transcription, tumor necrosis factor–induced activation of nuclear factor κB, and expression of cell adhesion molecules and protein kinases.3 We studied the efficacy of leflunomide in the treatment of patients with psoriasis with or without associated PA. The study included 10 patients (7 men and 3 women; age range, 23-67 years) with mild to moderate psoriasis (average duration of disease, 4-27 years). Five patients had only psoriasis vulgaris, involving 30% to 50% of their body surface area; 3 patients had psoriasis vulgaris with PA; and 2 patients had generalized pustular psoriasis. The drugs that the patients had used before leflunomide therapy included methotrexate, psoralen–UV-A, sulfasalazine, and cyclosporine with or without nonsteroidal anti-inflammatory drugs. The results of pretreatment evaluation, including a complete blood cell count, renal and hepatic functions tests, urinalysis, and chest x-ray films, were normal in all 10 patients. The pretreatment psoriasis area and severity index scores were recorded and compared every 2 weeks to assess the response to treatment. Joint disease was also evaluated with respect to pain intensity, swelling, discomfort, and deformity. All patients received a loading dose of leflunomide (100 mg/d for 3 days), followed by 20 mg/d for 6 to 8 months. No clinically remarkable improvement was observed in cutaneous lesions of either the plaque or the pustular type. A mild to moderate improvement in pain intensity, joint swelling, and physical activity was observed in patients with associated arthropathy. Leflunomide primarily exerts its activity through T lymphocytes, which may suppress proinflammatory T-helper cell, cytokine-mediated, epidermal cell proliferation of psoriasis. An upregulation of anti-inflammatory factors, such as interleukins 1 and 10 receptor proteins, may also produce an antipsoriatic effect.2-4 Leflunomide also inhibits epidermal cell proliferation through induction of negative cell cycle inhibitor p 53. Although improvement in joint erosions has been radiologically observed in a patient with PA, the efficacy of leflunomide therapy for psoriasis vulgaris has not been clinically proved.5 Our preliminary observations in this open trial of a small group of patients suggest that leflunomide fails to show clinical efficacy in psoriasis vulgaris despite its potential use as an anti-inflammatory and immunomodulatory agent in PA. However, although leflunomide therapy may be beneficial for patients with PA, further evaluation is needed. The authors have no relevant financial interest in this article. Correspondence: Dr Thami, Department of Dermatology and Venereology, Government Medical College and Hospital, Sector-32B, Chandigarh 160030, India (thamigp@yahoo.com). References 1. Reich KHummel KMBeckmann IMossner RNeumann C Treatment of severe psoriasis and psoriatic arthritis with leflunomide Br J Dermatol. 2002;146335- 336PubMedGoogle ScholarCrossref 2. Sanders SHarisdangkul V Leflunomide for the treatment of rheumatoid arthritis and autoimmunity Am J Med Sci. 2002;323190- 193PubMedGoogle ScholarCrossref 3. Pipitone NKingsley GHManzo AScott DLPitzalis C Current concepts and new developments in the treatment of psoriatic arthritis Rheumatology. 2003;421138- 1148PubMedGoogle ScholarCrossref 4. Brockbank JGladman D Diagnosis and management of psoriatic arthritis Drugs. 2002;622447- 2457PubMedGoogle ScholarCrossref 5. Cuchacovich MSoto L Leflunomide decreases joint erosions and induces reparative changes in a patient with psoriatic arthritis Ann Rheum Dis. 2002;61942- 943PubMedGoogle ScholarCrossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Oct 1, 2004

Keywords: arthritis, psoriatic,psoriasis,leflunomide

References