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Leflunomide is a disease-modifying anti-rheumatic drug (DMARDs), approved by Food and Drug Administration (FDA) to treat rheumatoid arthritis (RA).
Leflunomide is a disease-modifying anti-rheumatic drug (DMARDs), approved by Food and Drug Administration (FDA) to treat rheumatoid arthritis (RA). [1] It exhibits a substantial immunomodulatory and anti-inflammatory effect. It has shown significant efficacy in reducing the signs and symptoms and delaying disease progression in RA patients. It also helps to maintain function, limits irreversible joint damage and prevents synovitis in patients with RA. [2]
Pharmacological class: Pyrimidine synthesis inhibitor
Leflunomide acts by
suppressing dihydro-orotate dehydrogenase enzyme, which may further prevent synthesis of ribonucleotide uridine mono-phosphate
pyrimidine (rUMP) and reduced rUMP levels. This series of steps leads
to activation of p53, which restricts the
proliferation of autoimmune T cells and the production of auto-antibodies by B
cells. [2]
Leflunomide is contraindicated in:
Leflunomide is metabolized to teriflunomide after oral administration. All the drug interactions studies of leflunomide have been carried out with its active metabolite teriflunomide.
These studies have reported that:
Therefore, close monitoring of people should be done, and
the dose of teriflunomide should be modified if co-administered with
above-mentioned drugs. [3]
Common adverse events associated with the leflunomide were:
Nausea, diarrhea, dyspepsia, respiratory infection,
headache, rash, and abnormal liver enzymes
Serious adverse events associated with leflunomide were:
Hepatoxicity, immunosuppression, bone marrow suppression, peripheral
neuropathy, interstitial lung disease and Stevens-Johnson syndrome
Less common adverse events associated with leflunomide
were:
Various clinical trials
have demonstrated the efficacy and safety of leflunomide compared to placebo
and other anti-rheumatic drugs in managing patients with RA. A brief summary of
these trials is explained as below:
Efficacy and safety of leflunomide to treat rheumatoid arthritis:
In early rheumatoid arthritis people having moderate or mild disease activity, a 50 mg/week leflunomide exhibited comparable benefits to a daily dose of 10 mg leflunomide. This randomized, multi-center study aimed to assess the safety and efficacy of weekly administration of leflunomide for rheumatoid arthritis.
Participants were segregated to either the treatment group (50 mg/week leflunomide, LEF50) or the control group (10 mg/day leflunomide, LEF10). All the recruited subjects were treated for twenty-four weeks. Using European League Against Rheumatism (EULAR) response and disease activity score in 28 joints (DAS28) - erythrocyte sedimentation rate (ESR) response, evaluation of clinical efficacy was done.
Overall, 244 people fulfilling the inclusion criteria and receiving at least 1 medicine dose were evaluated. The DAS28 (ESR) in the study groups declined at week 24 than the baseline. At week 24, no profound differences were noted in DAS28 (ESR) between the study groups. Similarly, no profound differences in EULAR response (good responses + moderate responses) rates were noted in the study groups at weeks eight, twelve, and 24, as shown in the table below:
No severe side effects were witnessed. Thus, management of rheumatoid arthritis with a weekly dose of leflunomide is easy and has an excellent safety profile. [4]
In another retrospective assessment of data from the PLUS study, it was reported that treatment with standard doses of leflunomide is safe and permits a remarkable clinical improvement in people suffering from RA. [5]
Leflunomide vs. methotrexate for rheumatoid arthritis:
In a systematic review and meta-analysis of clinical studies carried out by Roberto Alfaro-Lara et al., leflunomide used as the first DMARD in rheumatoid arthritis appeared to be as efficacious as methotrexate.
This study aimed to explore the efficacy and adverse effects
of methotrexate and leflunomide in rheumatoid arthritis people as the first
disease-modifying anti-rheumatic agent. Overall, 1984 participants were
incorporated: 998 were given methotrexate and 986 were given leflunomide.
Leflunomide showed similar efficacy as methotrexate. Fewer
gastrointestinal complaints were reported with leflunomide therapy. [6]
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