Rituxan (rituximab) in rheumatoid arthritis may cause Progressive Multifocal Leukoencephalopathy: FDA Alert

Rituxan was reported to be associated with progressive multifocal leukoencephalopathy (PML). In an alert issued recently by Genentech and FDA, rituximab (Rituxan) was used in a patient with rheumatoid arthritis who has not previously treated with any TNF antagonist. This would be the first case of rituximab-associated PML in rheumatoid arthritis. Previously there have been 2 other rituximab-associated PML cases.

Genentech, the company that produced Rituxan, said that the incident is very low, there were only three cases out 100000. Genentech was trying to expand the use of Rituxan to include earlier stage of rheumatoid arthritis, but FDA has disapproved it due to the recently reported PML.

The FDA said that:
"Physicians should consider PML in any patient being treated with Rituxan who presents with new onset neurologic manifestations. Consultation with a neurologist, brain MRI, and lumbar puncture should be considered as clinically indicated."

Do Psychological Problems Activate the Symptoms of Rheumatoid Arthritis?

Do psychological factors have anything to do with rheumatoid arthritis? In other words, if a patient is having a pyschological problems such as a depression or anxiety, would it it mean that she/he will have her/his symptoms of rheumatoid arthritis activated?

This is not an easy question to answer, because we are seeking causality here. Simply put, does psychological factors activated rheumatoid arthritis? We can easily see that psychological factors may co-exist with an active rheumatoid arthritis, but that should not be necessarily mean that the one causes the other or vice versa; it could simply mean that they are there together without any relation.

That is the challenge that Dr. Kojima and the colleagues from the Department of Medicine, Shinshu University, Asahi Japan, want to answer when they did a research on psychosocial factors, disease status, and quality of life in patients with rheumatoid arthritis.

Dr. Kojima and the colleagues studied 120 outpatients with rheumatoid arthritis. The patients were asked to have a series of health examinations and questionnaires. They want to explore whether there is any relationship between the psychosocial and illness factors which in turn would have something to do with the disease status of patients with rheumatoid arthritis.  Also, they want to know how each factor is associated with the quality of life of those patients.

The study found no significant association between psychosocial factors and disease activity, but yes physical quality of life of the patients depended on current symptoms and their physical functions. To put it in a simple way, may be we can safely say that psychological problems would not cause your rheumatoid arthritis to be activated, but of course the severity of the symptoms and disabilities would compromise your enjoyment of life.

(Source: Journal of Psychosomatic Research, J Psychosom Res 2009 Oct 20; Vol. 67, Issue 5; Page(s) 425-31)

An Overview on the Symptoms of Rheumatoid Arthritis

Rheumatoid arthritis is the second most common form of arthritis after osteoarthritis. Arthritis is a group of diseases which share common symptoms, i.e. joint pain; yet each of them has certain unique characteristics and different underlying etiology.

Rheumatoid arthritis is an autoimmune disease, which means that our immune system mistakenly interpret certain parts of our own organ system as a threat. In rheumatoid arthritis, it is the joint, especially the lining system that is under attack. This odd pathologic mechanism leads to characteristic symptoms of rheumatoid arthritis such as swelling, redness, pain and even disabilities. Due to its systemic nature, the erratic immune system in rheumatoid arthritis not only affects the joints, it also attacks other organs like eyes, lungs, blood vessels and heart. Osteoporosis secondary to rheumatoid arthritis is also a common finding, and treatment with glucocorticoids may further contribute to the worsening of osteoporosis.

The rheumatoid arthritis symptoms is usually begins with insidious vague fatigueness, anorexia, generalized weakness and unobvious muscle pain. The symptoms may persist for weeks or months, and can be viewed as prodromal symptoms of rheumatoid arthritis. This prodromal state usually end after the joints inflammation become apparent.

Morning stiffness is a famous feature of arthritic diseases. It is a generalized joint stiffness which usually last not more than an hour in the morning and disappear when the patient begins her/his daily activites.

The joints pain in rheumatoid arthritis most usually takes a symmetrical pattern. It typically affects multiple little joints in both hands and/or feet. It can also damage bigger joints such as the ankles, knees and elbows. About one out of three patients who suffered from rheumatoid arthritis will develop subcutaneous rheumatoid nodules which usually found near the joints structure but can also grow in hidden places such as in the pleura (a thin lining at the surface of the lungs) and the meninges that covers our brain.

The symptoms of rheumatoid arthritis usually take a chronic course with remissions and acute phases. During remission periods, the symptoms of rheumatoid arthritis usually disappear but will return once the disease becomes active again. Joint damage takes a long course to finally debilitate the patient. This course can be slowed down with the use of modern medications known as disease modifying anti-rheumatic drugs (DMARDs).

Treatment of Rheumatoid Arthritis

Rheumatoid arthritis is a disease with unknown cause, at least until the time of this writing, hence there is no definitive, once and for all, treatment available today. This is an inflammatory disease with swollen, stiff, and painful joints as its main symptoms, which leads to impairment of movements and  deformities of the joints. This handicap will eventually affect the person both mentally and physically.

Educating the patient is the most important thing a doctor should do the first time a patient is diagnosed as having rheumatoid arthritis. Any patient should have a clear understanding of what is going on in her/his body, what would be expect to happen in the future, and what kind of change should she/he do now to anticipate it, this including kind of things that she/he might not be able to change. All this knowledge should be made available to the patient in such a way that it will give them a positive attitude toward their condition. Instead of feeling sad and worry about their future, the patient should be encouraged to do something about it and control it. Education should also include the types of proper  exercises, proper rest, and kind of diet that she/he would have to watch.

Treatment of rheumatoid arthritis is a race against time. It should be started as soon as the patient is diagnosed as having rheumatoid arthritis. The patient and the doctor should closely cooperate to have common terms and targets. More delay will eventually lead to more probability of joint damage. In other words, time is joint.

Non-steroidal anti-inflammatory drugs (NSAIDs) is a group of drugs which usually become the first drug that a doctor would prescribe to any patient with arthritic pain. These are the painkillers as we all know, but their main mode of action is as anti-inflammation. Aspirin is the most popular example, while coxibs is a group of more recently found NSAIDs. As painkiller, these drugs are of great help in acute conditions, but they do not have many impact on long time progress of the disease.

Glucocorticoids  are also used to reduce inflammation. These drugs is usually used as a single drug or  in combination with other group of drugs which called disease modifying anti-rheumatic drugs (DMARDs). This later group play an important role in modern treatment of rheumatoid arthritis.

The long known traditional DMARDs are hydroxychloroquin, methotrexate, sulfasalazin and the more recent leflunomide. Modern DMARDs are usually referred to as biological DMARDs which include drugs such as rituximab, adalimumab, etanercept, abatacept, and infliximab. These drugs help in reducing the long time impact of rheumatoid arthritis such as disability and joint damage, but due to their side effects they should be administered under close observation. The patient should be well informed concerning the expected result.