The use of Sandimmun (cyclosporin A) in severe refractory rheumatoid arthritis: the Belgian experience

OBJECTIVE: To investigate practicability, efficacy and tolerability of low
starting doses of Sandimmun (cyclosporin A) (2.5 mg/kg daily) in patients with
severe refractory rheumatoid arthritis in the short (6 months) and middle (12
months) term. METHODS: Fifty-nine patients, presenting with active and severe
rheumatoid arthritis unresponding to conventional DMRADs were allowed to start
Sandimmun at the dose of 2.5 mg/kg daily. This dose was progressively increased
by steps of 25 mg daily up to a maximum of 5 mg/kg daily according to the renal
function and blood pressure. RESULTS: A mean maintenance dose of 3.9 mg/kg daily
was reached after 5 months and maintained throughout the study. Twenty-one
patients (36%) completed the one year study. The reasons for discontinuation
were: inefficacy (13), adverse events (17), both inefficacy and adverse events
(5) and non-compliance (3). For those patients who completed the trial, clinical
relevant improvements were observed within 3 months of treatment and were
maintained until the end of the study for the Lee functional and the Ritchie
articular index, as well as for the number of tender and swollen joints. No
changes for the grip strength, the biological and immunological parameters were
observed. Mean serum creatinine values rose from 0.81 mg/dl at start to 1.1 mg/dl
after 5 months of therapy and remained at that level throughout the study. In
patients who discontinued, the serum creatinine level nearly normalized after one
month of Sandimmun withdrawal. One hundred and sixty-two side effects were
reported of which most were minor and known to occur with Sandimmun. Twenty-two
cases (37% of patients) dropped out for adverse events before 1 year treatment.
The criteria to withdraw the patients from the study differed greatly from centre
to centre. CONCLUSIONS: Managing RA patients presenting with very long and severe
disease remains difficult. Therefore low dose Sandimmun (2.5-5 mg/kg daily)
appears to be a valuable therapeutic opportunity in RA patients refractory to
various other conventional drugs, including methotrexate.