Lymphocyte depletion with fludarabine in patients with psoriatic arthritis: clinical and immunological effects.
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 > or =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.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. takadak@mail.nih.gov
K
K
Takada
C L
CL
Danning
T
T
Kuroiwa
R
R
Schlimgen
I O
IO
Tassiulas
J C
JC
Davis
C H
CH
Yarboro
T A
TA
Fleisher
D T
DT
Boumpas
G G
GG
Illei
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015535:Arthritis, Psoriatic / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000097:blood; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010766:Phosphorylation; D011241:Prednisone / Q000627:therapeutic use; D050794:STAT1 Transcription Factor; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology; D015534:Trans-Activators / Q000097:blood; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; D019040:E-Selectin; D007166:Immunosuppressive Agents; D019007:P-Selectin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D018799:Intercellular Adhesion Molecule-1; D014740:Vidarabine; C024352:fludarabine; D011241:Prednisone