Leflunomide vs Methotrexate

Many patients wonder which is more effective leflunomide or methotrexate.
Generally, methotrexate appears more effective in RA treatment than leflunimide and the latter is commonly used as an alternative or a part of a complex therapy when methotrexate fails. Not every patient seems to respond to methotrexate or tolerate it well and many of them show improvements after switching to leflunomide.
The effectiveness of these medications differs from patient to patient.

Specifically, in a study concerning the effectiveness of both these medications for juvenile rheumatoid arthritis (JRA) both these medications were found safe and more effective than the researchers expected. Specifically, response rate from methotrexate was 89% vs 68% from leflunomide, while the expected rates were 40% to 50%.

Leflunomide and Methotrexate Studies

The beneficial effect of methotrexate / leflunomide combination on active RA was confirmed in a number of studies.
A 24 week double-blind placebo-controlled trial involving  263 patients aged 18 to 75 was conducted in order to study the safety and effectiveness of the taking leflunomide with methotrexate in RA patients. Specifically, 130 patients were given combine treatment with methotrexate and leflunomide and 133 subjects were randomly placed on placebo and methotrexate.  The study showed that the combined treatment was generally well tolerated and the improvement of RA in patients receiving the combined treatment was better than in those on methotrexate and placebo. For this reason,
the combination of leflunomide with methotrexate was suggested as a possible alternative for active RA patients where methotrexate fails to improve the disease.

Overreaction of the immune system is typical for healthy, young people. It is considered to be the major cause of death from pandemic outbreaks of flu. The suggestion is thought to be true for the early stages of “swine flu” (H1N1). Abatacept (Orencia) has been approved by FDA for the treatment of rheumatoid arthritis, but not for the treatment of influenza yet.

The efficacy of the drug was tested on mice. It was found that the survival of mice treated Abatacept (Orencia) was 30% higher than among the untreated mice given the lethal dose of the virus influenza A. Recovery time was shorter and lung damage less severe among the mice treated with Abatacept (Orencia). Researchers found that the treatment diminished the tissue damage resulting from the immune overreaction and still allowed the body to combat the virus. The survival rate among the treated mice was considerably higher – 80% against 50% among the untreated mice.

The effect of leflunomide on the disease is still to be tested.

Currently three types of seasonal influenza are known: A, B and C. There is a number of Influenza A subtypes of including the recently discovered strain H1N1 also called “swine flu”. Today vaccination remains the most effective method of preventing the influenza virus infection. The popular antiviral drug, Tamiflu (Oseltamivir) stops the virus multiplication when taken within the first 2 days of influenza symptoms.

Source: http://www.arthritistoday.org/news/arthritis-drug-flu.php

Leflunomide acts slowly, it as also referred to as a “slow-acting” medication which improves rheumatoid arthritis over 3-12 months. It decreases the number of sick joints, improves pain, and leads to better overall assessments of disease activity. It is both effective and safe compared to other anti-rheumatic medications.

Leflunomide is also called a disease modifying medication, it sounds more impressive than slow-acting. The reason for introducing sych terminology is that reducing joint inflammation also results in improved function and better quality of life. In the long-term it also decreases the progression of joint damage.

LEF is an oral drug that is rapidly absorbed from the gastrointestinal tract. Leflunomide is a prodrug. This means it must be changed by patients’ own metabolisms into the active drug.

This transformation occurs in the patient’s stomach and blood soon after leflunomide is taken. Once absorbed, LEF is converted to its active form, a malononitrilamide known as teriflunomide.

The effect from leflunomide is acheieved by “turning off” the lymphocytes that attack joints. These lymphocytes are one of the major cell type causing inflammation in arthritis. In scientific terms, it the effect is acheved by the inhibition of the synthesis of a pyrimidine known as ribonucleotide uridine monophosphate pyrimidine

Leflunomide Clinical Trials

Six major clinical trials have determined that leflunomide is effective in arthritis treatment. Four of them were original research studies and the other two were follow up researches. All the trials lasted up for up to 2 years and involved 206 to 999 patients.

The conventional way to measure improvement is to assess the number of patients who improve by 20% or more on a range of measures of disease activity. Between 50% and 60% of patients improve by this amount when given leflunomide for 6 and 12 months. Without treatment less than 30% would improve in this way. These improvements are similar to those seen with other disease modifying drugs like methotrexate and sulfasalazine.

The number of patients who improve by 50% or 70% or enter remission also increases with leflunomide, though only a minority of patients will show such impressive results.

Arava (leflunomide) was unanimously recommended by the FDA (United States Food and Drug Administration) arthritis advisory committee to treat active rheumatoid arthritis in august, 1998 and fully approved on September 11, 1998.

At that time, leflunomide (brand name Arava) became the first new disease-modifying anti-rheumatic drug (DMARD) aimed to treat of rheumatoid arthritis in more than ten years’ period.

Leflunomide Tests

Prior to being recommended and approved, leflunomide has been tested against other widely used rheumatoid arthritis medications, such as methotrexate. Over 480 americans with moderate rheumatoid arthritis participated in the tests. As a result, about 41 % of patients taking Arava (leflunomide) achieved improvement in their physical condition against only 19 % of those treated by placebo. Patients taking methotrexate experienced approximately the same effect as those thaking Arava (leflunomide).
X-rays examination of the patients’ joints revealed that with Arava (leflunomide) arthritis progressed for times as slowly as with placebo. Methotrexate proved to be more effective is slowing arthritis progression than placebo, but not as effective as Arava (leflunomide).
Another “pro” was that Arava (leflunomide) side effects were reversible and not severe, compared to methotrexate which was associated with the risk kidney failure in some cases. In addition, methotrexate lost effectiveness over time. Such difference was observed because Arava (leflunomide) and methotrexate target different enzymes while suppressing the overactive immune system. However, the basic principle of work remains the same – suppressing an overactive immune system.
Arava (leflunomide) proved to be more safe an effective than other rheumatoid arthritis drugs.