Cyclosporin A in severe, treatment-refractory rheumatoid arthritis. A randomized study.
OBJECTIVE
To assess the efficacy and toxicity of cyclosporin A in patients with severe, treatment-refractory rheumatoid arthritis.


METHODS
Prospective randomized, double-blind 6-month trial.


METHODS
Thirty-one patients who had classic seropositive rheumatoid arthritis with active synovitis unresponsive to conventional therapy.


METHODS
Patients were randomly assigned to high-dose (10 mg/kg body weight.d) or low-dose (1 mg/kg.d) cyclosporin A therapy. A reduction in the dose was permitted for adverse side effects. After 6 months of therapy, patients who showed clinically relevant improvement, defined as a 40% or greater reduction in their total joint activity score, were given the option to continue receiving the therapy for an additional 6 months.


RESULTS
At 6 months, clinically relevant improvement occurred in 10 of 15 patients (95% CI, 38 to 88) receiving high-dose therapy and in 4 of 16 patients (CI, 7 to 52) receiving low-dose therapy (P = 0.02). Statistically significant improvements in individual measures were shown only in the high-dose group. Improvements were noted in the number of tender joints (-18.8; CI, -24.5 to -13.1) and swollen joints (-12.1; CI, -15.4 to -8.6), as well as in physician's global scores (-1.5; CI, -2.1 to -0.9) and patient's global scores (-1.1; CI, -1.9 to -0.5). Improvement in disease activity was maintained through 12 months in the high-dose group. The clinical responses to cyclosporin A were most evident in patients with depressed in-vitro proliferative responses of peripheral blood mononuclear lymphocytes to soluble recall antigens. Toxicities, such as fatigue, gastrointestinal and neurologic complaints, and hypertrichosis were frequent but often reversible with a reduction in the dose. Nephrotoxicity, with a 20% increase in the serum creatinine level, was seen in 27 of 31 patients (CI, 71 to 97).


CONCLUSIONS
Cyclosporin A is an effective therapy for severe, treatment-refractory rheumatoid arthritis. Side effects, particularly nephrotoxicity, are common.
Yocum
D E
DE
National Institutes of Health, Bethesda, Maryland.
Klippel
J H
JH
Wilder
R L
RL
Gerber
N L
NL
Austin
H A
HA
Wahl
S M
SM
Lesko
L
L
Minor
J R
JR
Preuss
H G
HG
Yarboro
C
C
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D002097:C-Reactive Protein / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D011446:Prospective Studies; D011897:Random Allocation
D003524:Cyclosporins; D002097:C-Reactive Protein; D003404:Creatinine