Click here to view next page of this article


Rheumatoid Arthritis

Rheumatoid arthritis is the commonest of the inflammatory arthritides. Some new data I am going to share with you and new thoughts on the disease, first of all there is rapid radiographic progression in the first three years. Number two is the disease is worse in women than men. It progresses more rapidly in females than males. There is a higher death rate in patients with extraarticular disease such as neuropathy, skin ulcers, that makes sense. Wolf in Wichita, Kansas did a age match/sex match control male/female basically, if you have the diagnosis of rheumatoid arthritis your morbidity goes up 2.3 in women and 2.1 in men versus controls.

What else? We think there is a two-year therapeutic window, the disease responds best in the first two years of therapy. It seems that the immune responses are not set in stone. It seems that the immune responses respond better early. Patients develop erosive disease early, although not all patients do, we are looking for a marker to determine why some patients donít develop erosive changes and why most do. The longer the disease remains untreated the worse the outcome. Immune mechanisms involved may be more vulnerable early. Improvement in function inflammation did not occur in parallel, which means that, if you had the disease for three years and I get rid of your pain and stiffness.

These days we do not have a specific test for outcomes in rheumatoid arthritis so we do it clinically. What do we do these days? We can deplete T-cell populations, we can block cyctokines, and we can modify leukocyte adhesion. This is important and I will just mention this and move on, leukocyte adhesion is being looked at in cancer patients. The idea is that if you canít have cells migrate and stick to vessel walls or develop new blood cells, angiogenesis, you canít supply synovium in rheumatoid arthritis and you cant supply tumors. Cells have to migrate to the site through vessel walls and new blood vessels have to be built to supply the new synovium or a tumor. There is a lot of work being looked at now in terms of blocking angiogenesis and preventing neutrophils from sticking to blood vessels. That is going to be the state-of-the-art. Right now, there is a lot on cytokines and that is what is new in rheumatoid arthritis. The adhesion molecules and angiogenesis are in the future and in the wings and offer a great promise.

General approach, early intervention, selection of the drug based on the disease activity functional status etc. milder disease, we use Plaquenil and sulfasalazine. Aggressive disease we still use Methotrexate. Steroids are a bridging medication. Cortical steroids work as an anti-inflammatory, they are not really a disease modifying medication.

New medicines, the Cox II inhibitors, what do they do? Cox II is inducible and thatís inflammation. Cox I is constitutive means you need it. The older antiinflammatory medications blocked both of these enzymes, which led to their side affects. For example, Cox I is associated with renal blood flow, hypertension, kidney function, GI homeostasis, peptic ulcers etc. Maybe some pulmonary components as well and of course, platelets, they cause platelets disfunction and bruising.

The new Cox II and there are two of them on the market right now, Vitax and Celebrex block only in their standard dosages inflammation without inhibiting Cox I, that is their benefit. As an anti-inflammatory they probably offer no increased efficacy in terms of working but they offer a better safety profile, so in specific patients they are quite helpful.

Methotrexate is our goal standard these days. It is a drug you are going to see patients on. There is a lot of argument that we should be using higher doses. We have been starting out at usually 10, a lot of people want to try 25 right off the bat. The higher the dose probably more side affects.

We have left the day of monoarticular therapy and rheumatoid arthritis everything is boiling down to combinations. The two newer ones are at the bottom, Methotrexate and Enbrel, Methotrexate and Remicade. Leflunomide is a new chemical, similar to Methotrexate that is also on the market. In the past two years, we have two tumor necrosis factorial medications, we have a new remitive drug and Leflunomide and we have the Cox II inhibitors.

Tumor necrosis factor alpha is a cytokine that is at the peak of the inflammatory response, you inhibit that, you inhibit inflammation. You are not altering the disease mechanisms per say, your blocking inflammation. Two drugs have been released that are affective against it, one of them is Enbrel and Etanercept, that is what it looks like to try molecule. What it does is prevent activation of cells by tumor necrosis factor in blocking inflammatory cascade. This is what the molecule looks like, it is injected twice a week. It is effective within the first 8 weeks of therapeutics.

The second drug is an antibody Remicade Infliximab, it is given 3 to 10 mg IV infusion, and it is a larger molecule, looks like that. It is a big molecule as opposed to a smaller one. It has the potential to insight antibody production of yourself against it. Interestingly they did a study, the bottom line is no therapy. The upper two lines are Methotrexate and without Methotrexate. The efficacy is increased with Methotrexate probably because Methotrexate seems to prevent antibody formation against the Remicade. Remicade is a IV infusion that is given initially every couple of weeks and maintenance every two months. Initially designed for use in Crohnís disease and it has been published in the England Journal of Medicine.

Azathioprine, a drug we have used for years. Antibiotics questionings about Minocycline. I have not had much success to the adding of tetracycline or minocycline or tetracycline in rheumatoid arthritis, some studies say it is effective early in the disease, most of the people we have used it on is later in the disease. Cyclosporin, good medication, too many side affects, not good as monotherapy, effective in combinations.

Prosorbacolumn, just recently approved by the FDA, really difficult to understand how this works, whether something is a release from the column or something is taken out by the column, but seems to be effective in refractory arthritis, it does require good IV access and its 12 weeks in a row. It is a difficult therapy to use, per se, I havenít used it in any patients yet. But, that may be effective in people with severe disease. Osteoarthritis we mentioned, refractory we will skip.

We will just move on to osteoarthritis and talk about osteoarthritis in general. I have a relatively complete list of things we do in terms of therapeutics. I want to mention a couple of things Iíve got a little bit of time left. In your clinical practice, the commonest thing you will see are cervical and lumbar stenosis, neck and back, plus osteoarthritis. As the population ages this is what we see lots of. I keep the orthopedic back surgeons very happy because I make that diagnosis three times a week and send them at least three or four patients a week either with cervical or lumbar disease.

Mike mentioned lumbar stenosis, the pseudoclaudication syndrome, I will mention cervical stenosis. Cervical stenosis presents with lower extremity weakness and hyperreflexia. It can also present with a much more difficult vertricular basilar insufficiency syndrome. Dysphasia, Diplopia, dizziness, vertigo, all related to compression of the arterial circulation of the back of the neck by osteophytes. You can have a cervical stenosis syndrome with weakness in the legs, you can have a vestibular basilar insufficiency syndrome, which is difficult to diagnose. Then, of course, you can then have the typical cervical radiculopathy with pinched nerves. Meaning, I can either get cervical cord compression in the neck, I can get neural foramen compression in the neck.