Research on Cyclosporine

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Converting RA Patients to the

Microemulsion Formulation of Cyclosporine

Paper: Conversion of patients with rheumatoid

arthritis from the

conventional to a microemulsion formulation of

cyclosporine: a double blind

comparison to screen for differences in safety,

efficacy, and

pharmacokinetics.

Authors: IF, et al.

Ref: J Rheumatol 1999;26:556-562.

Type: Clinical Study

Summary: Variability in the pharmacokinetics

of

conventional oral cyclosporine often make it

difficult to dose,

thereby resulting in unwanted side effects. A

new

microemulsion formulation of this drug, with

more predictable

kinetics, demonstrated similar efficacy and no

improvement

in tolerability.

The use of conventional oral cyclosporine

(CyA) has been

shown to be effective in improving subjective

and objective

disease variables in patients with advanced

rheumatoid

arthritis (RA). However therapy with

conventional CyA can

be complicated by the variability in its

pharmacokinetics. In

patients where side effects are dose limiting,

this variability

may be clinically important. A new

microemulsion

formulation of cyclosporine has been

developed. This

formulation has exhibited improved dose

linearity, reduced

intraindividual variability, and improved

bioavailability.

Preliminary findings suggest that these

factors result in a

good safety and tolerability profile. This

study was performed

to screen for differences in the safety,

tolerability, and

efficacy of a milligram-to- milligram

conversion from

conventional CyA to microemulsion CyA in

patients with RA

over a 52 week period.

The study was a double-blind, multicenter,

parallel group

study that enrolled 51 patients already taking

conventional

CyA. Conventional CyA was continued in 27

patients and 24

patients converted to the CyA microemulsion.

At regular

intervals trhoughout the study the efficacy of

both CyA

formulations was measured. No clinically

relevant difference

in efficacy between the two groups was found,

and this was

true of assessments by both investigators and

patients.

However, the conversion of the formulation of

CyA did not

alter the incidence of adverse effects.

Adverse effects were common in both groups,

however the

incidence and nature of adverse effects was

not significantly

different between the groups. Dose reductions

for safety

reasons and dosed increases were carried out

in similar

proportions of patients in each group. The

pharmacokinetic

parameters in the conventional group were

unchanged while

the microemulsion group demonstrated a

significant increase

in the rate and extent of CyA absorption. The

intraindividual

variability in pharmacokinetics was

numerically lower in

patients converted to microemulsion

formulation. However,

the interindividual variability was not

markedly different

between the formulations. The increased

exposure of

cyclosporine provided by the microemulsion was

not found to

adversely affect kidney function in comparison

to similar

doses of conventional CyA.

The authors concluded that the results of this

study confirm

results from other indications and

substantiate the suitability

of recently published dosing guidelines for

the use of

microemulsion formulation of CyA in rheumatoid

arthritis.