An open label, single dose study to evaluate the safety, efficacy, and effects on CD25 expression of ciclosporin in patients with active rheumatoid arthritis despite treatment with methotrexate and infliximab.
OBJECTIVE
To explore the safety, efficacy, and lymphocyte activation of a triple therapeutic regimen with infliximab, methotrexate (MTX), and ciclosporin A (CsA) by an open label, pilot study.


METHODS
19 patients (mean age 52.9 years) with active rheumatoid arthritis (mean DAS28 7.3) after a mean of 16.8 infliximab infusions and dose adjustments of both infliximab and MTX were enrolled. CsA was added to a stable therapeutic regimen. Disease activity was evaluated by the DAS28. Lymphocyte activation was evaluated by assessing CD25 expression on peripheral blood mononuclear cells (PBMCs). Primary end points were safety and efficacy according to the EULAR response criteria at 24 weeks.


RESULTS
Eight patients (42%) discontinued treatment: adverse events (3), inefficacy (2) or non-compliance (2). One patient had a stroke and died. 5/11 (45%) patients who completed 24 weeks' treatment were moderate responders. CD25 expression, both on unstimulated and phytohaemagglutinin stimulated PBMCs in five patients assessed, was reduced (mean (SD) values from 37 (34)% to 15 (10)% and from 50 (15)% to 29 (20)%, respectively).


CONCLUSIONS
In this group of patients with refractory, highly active disease, addition of CsA reduced lymphocyte activation, and resulted in a modest response and a high rate of discontinuation. In such patients, other new approaches need to be explored.
Sidiropoulos
P I
PI
Department of Rheumatology, Clinical Immunology and Allergy, University of Crete, University Hospital, Heraclion, Greece.
Siakka
P
P
Raptopoulou
A
A
Mamoulaki
M
M
Choulaki
C
C
Koutala
H
H
Kouroumali
H
H
Kritikos
H
H
Boumpas
D T
DT
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D000069285:Infliximab; D008727:Methotrexate