Tacrolimus Appears to be Safe, Effective Treatment for Rheumatoid Arthritis

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Tacrolimus Appears to be Safe, Effective Treatment for Rheumatoid Arthritis

A DGReview of : " Efficacy and safety of tacrolimus in patients with

rheumatoid arthritis: A double-blind trial "

Arthritis & Rheumatism

12/31/2003

By Beth Nierengarten

Monotherapy with tacrolimus is safe and effective for patients with active

rheumatoid arthritis (RA), reports a multicentre study from the United

States.

Tacrolimus is an immunomodulatory and anti-inflammatory agent that is used

to prevent organ transplant rejection, and has recently shown efficacy in

phase II testing for RA patients resistant to or intolerant of methotrexate

therapy.

In this phase III, double-blind study, E. Yocum, MD, University of

Arizona, and colleagues assessed the safety and efficacy of tacrolimus as

monotherapy for patients with RA. The 6-month study included 464 patients

with active RA; 154 of the patients were randomised to 2 mg of tacrolimus,

153 to 3 mg of tacrolimus, and 157 to placebo. Patients were stratified

according to whether they were intolerant or resistant to disease-modifying

antirheumatic drugs (DMARDs). Efficacy was based on criteria established by

the American College of Rheumatology (ACR) that defined improved response as

=/> 20% (ARC20), =/>50% (ARC50), or =/>70% (ARC70). Completion of 6 months

of treatment and an ACR20 response at the month 6 visit was defined as an

ACR success. Improvement was measured in the tender/painful and swollen

joint counts as well as improvement in 3 of 5 parameters based on the visual

analog scale (VAS) to measure pain and disease activity, modified Health

Assessment Questionnaire to measure physical function, and the erythrocyte

sedimentation rate (ESR) or C-reactive protein (CRP) to assess acute-phase

reactant levels.

At 6 months, significantly more patients treated with 2 mg (18.8%) and 3 mg

(26.8%) of tacrolimus had a ACR20 success rate compared to placebo (10.2) (P

< .05 and P < .0005, respectively). Patients treated with 3 mg tacrolimus

had significantly superior ACR20 (32%) and ACR50 (11.8%) response rates at

the end of treatment compared to placebo. For patients who were

DMARD-intolerant, ACR response rates were better than for those

DMARD-resistant.

Throughout the study, the serum creatinine level remained within normal

range in about 90% of the patients, although increases equal to or greater

than 40% from baseline measures to some point during treatment were seen in

20% of patients treated with 2 mg tacrolimus and 29% treated with 3 mg

tacrolimus.

Overall, tacrolimus was well-tolerated over the 6-month study period, with

flu syndrome, diarrhoea, nausea, dyspepsia, and headache reported as the

most common adverse events.

The authors conclude that tacrolimus is safe and effective in patients with

active RA and that the study demonstrated a dose-response relationship " with

a single daily dose of 3 mg being more effective than the lower dose of 2

mg. " In addition, the study found that tacrolimus is more effective in

patients intolerant to DMARDs compared to those resistant to DMARDs.

Arthritis Rheum. 2003 Dec;48:12:3328-3337.