Abstract
Combination of disease-modifying antirheumatic drugs (DMARDs) is increasingly used
in the treatment of rheumatoid arthritis (RA) patients. Hepatotoxicity has been an
important safety concern with DMARDs therapy. Though leflunomide (CAS 75706-12-6)
has emerged as an effective oral DMARD, its use is associated with hepatotoxicity.
Limited data is available regarding hepatotoxic risk when leflunomide is used in combination
therapy in RA patients. An open-label, prospective study was conducted to evaluate
the hepatotoxic risk after addition of leflunomide with other DMARDs in RA patients,
who did not respond to their ongoing DMARD therapy. A total of 46 patients were enrolled
and leflunomide was given as add-on therapy with earlier DMARDs. Biochemical parameters
of serum aminotransferase levels (AST and ALT) were estimated at the baseline and
then every month after addition of leflunomide. Study results showed that 13.0% patients
developed <1.5 to <2 times upper limit of normal (ULN) elevation; 6.5%patients developed
2 to <3 times the ULN elevation and 2.2% patients developed >3 times the ULN elevation.
In 20% of the patients with hepatic enzyme elevations, enzyme levels returned to normal
within 4–6 weeks after discontinuation of leflunomide therapy, whereas in 50% of patients
the dose of leflunomide was reduced from 20 mg/day to 10 mg/day for normalization
of enzymes levels. 30% of patients were continued with leflunomide without dose reduction.
None of the patients showed clinical signs and symptoms of hepatotoxicity. Leflunomide
therapy with other DMARDs requires strict monitoring of serum aminotransferases.
Key words
Add-on therapy - Disease-modifying antirheumatic drugs - Hepatotoxicity - Leflunomide
- Rheumatoid arthritis
