Leflunomide. Me

Leflunomide (LEF; Arava®) is an isoxazole derivative approved by the United States FDA for the treatment of rheumatoid arthritis (RA). Currently leflunomide is the only new disease-modifying anti-rheumatic drug to be introduced in the last two decades.
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 of 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.

Rheumatoid arthritis limited my abilities to exercise and made me feel like a cripple. I could only take short walks and do some simple aerobics for quite a long period but that was not enough for me to keep fit.  More active exercises made my joints swell and hurt afterwards. As a result, I was losing muscle weight and gaining fat. The idea of swimming was a blessing. I studied the subject and found that:

• Water exercise is a really gentle way to exercise joints and maintain muscle strength.
• Warmth and buoyancy of warm water create a safe, ideal environment for relieving arthritis pain and treating stiffness.
• Immersing in warm water raises body temperature, dilates blood vessels and improves blood circulation.
• Water allows free movement because it supports joints
• Using spa with massage adds beneficial component to the therapy: they improve blood circulation and relax muscles.

I’ve been going to the swimming pools local water fitness classes for 1 month now and I feel stronger and more energetic. I keep taking leflunomide and my joints condition is not worsening. That is good news!

Rheumatoid arthritis is a chronic inflammation of joints which in most cases affects the lining of the joint or synovium. Often, the disease continues indefinitely, progresses and results in long-term joint damage accompanied by chronic pain, loss of function or even disability. Rheumatoid arthritis is an autoimmune disease, which means that the inflammation is caused by the hyperactivity of the immune system which mistakenly attacks the body’s tissues in the manner it is supposed to attack invaders. Besides joints, rheumatoid arthritis can affect other organs in the body. About 1.3 million Americans suffer from rheumatoid arthritis.
Rheumatoid arthritis (RA) develops in three stages. The first stage is characterized by swelling around the joint , pain, swelling of the synovium, warmth and redness around it, stiffness of the joint. At this stage x-rays will not show any destructive changes, only the swelling of joint lining.
During the second stage inflamed synovium tissue starts to proliferate: synovium cells start rapid division and growing into joint cavity across articular cartilage, gradually narrowing and destroying it.
In the third stage, the inflamed cells release enzymes that cause erosion of bone and cartilage. Often, the joint becomes deformed and looses alignment. The pain becomes more severe and the ability to move is lost.
As of today, there is no specific cure for rheumatoid arthritis that guarantees recovery. However, certain drugs (including leflunomide), joint protection and self-management techniques, as well as diagnosing the disease at early stages and following the doctor’s recommendations allow to limit joint damage, keep it under control and live a productive and happy life.

Leflunomide History Flashback:

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