CONCISE REPORT

Lymphocyte depletion with fludarabine in patients with psoriatic arthritis: clinical and immunological effects

K Takada¹, C L Danning², T Kuroiwa³, R Schlimgen⁴, I O Tassiulas⁵, J C Davis, Jr⁶, C H Yarboro¹, T A Fleisher⁷, D T Boumpas⁸ and G G Illei¹

¹ National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institues of Health, DHHS, USA
² Gundersen Lutheran, USA
³ Third Department of Internal Medicine, Gunma University School of Medicine, USA
⁴ Department of Immunology, Duke University Medical Center, USA
⁵ Hospital for Special Surgery, USA
⁶ Division of Rheumatology, University of California San Francisco, USA
⁷ Immunology Service, Department of Clinical Pathology, Warren Grant Magnuson Clinical Center, National Institutes of Health, DHHS, USA
⁸ University of Crete Medical School, Greece

Correspondence to:
Correspondence to:
Dr Kazuki Takada, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 9S-205, Bethesda, MD 20892, USA; takadak{at}mail.nih.gov

Objective: To obtain preliminary information on the safety and efficacy of fludarabine in PsA and analyse its immunomodulatory effects in peripheral blood and synovial tissue.

Methods: 15 patients with active PsA who did not respond to DMARDs were randomly allocated to receive fludarabine every four weeks or placebo. Primary outcomes were the proportion of patients who met the ACR20 and the psoriatic arthritis response criteria (PsARC) at 16 weeks. Secondary outcomes were changes in tender or swollen joint counts and scores of the psoriasis area and severity index (PASI). Phenotypic analysis of peripheral blood mononuclear cells (PBMC), synovial immunohistochemistry, and functional analysis of PBMC were used to determine the immunomodulatory effects of fludarabine.

Results: At 16 weeks the ACR20 criteria were met by 3/7 (43%) fludarabine treated v 0/8 placebo treated patients (p=0.08); the PsARC was achieved by 4/7 (57%) fludarabine treated v 2/8 (25%) placebo treated patients; and 3/7 (43%) fludarabine treated v 0/7 placebo treated patients had 20% improvement in the PASI. Marked peripheral lymphopenia involving naive (CD4⁺ CD45RA⁺) and memory (CD4⁺ CD45RO⁺) T cells, CD8⁺ T cells, and B cells was seen in fludarabine treated patients.

Conclusions: In PsA fludarabine induces significant peripheral, but modest, synovial lymphopenia, and a trend towards improved clinical response.

Keywords: psoriatic arthritis; psoriasis; fludarabine; randomised controlled trials

Abbreviations: ACR, American College of Rheumatology; DMARD, disease modifying antirheumatic drug; ICAM, intercellular adhesion molecule; PBMCs, peripheral blood mononuclear cells; PsA, psoriatic arthritis; PSAI, psoriasis area and severity index; PsARC, psoriatic arthritis response criteria

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