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Treatment of Rheumatoid Arthritis

There has been a significant amount of evidence that shows that disease activity early on causes significant problems, that we need to treat RA more aggressively, find more effective early treatment to try and rheumatoid arthritis, rumatoid arthritis decrease the morbidity, to try and decrease the mortality. There are many challenges. The disease is chronic rheumatoid arthritis, rumatoid arthritis. The disease can take a significant period of time to take effect. The patient’s course is very variable. Some patients have very mild disease, some people have very severe disease. How do we identify which people need more aggressive treatment? Some people will respond to one treatment other people won’t respond to it and it becomes very challenging.

Patient education can start from just simply explaining the disease to the patients. Most patients have a very poor understanding and it’s scary what they might find on the net. More and more of my patients were searching the Internet for information and I think they came back with more untested, unproven alternative therapies than real knowledge of what RA was. So it’s very important that we point them in the right direction.

There’s a lot of medication we can use. We all use all this stuff. We all use aspirin. Aspirin has always been sort of the gold standard because it’s the one we have the most tests on. But certainly we’ve used more of the traditional NSAID’s because they are more convenient, they are probably much less toxic than aspirin itself. We are going to talk about NSAID’s next hour, about certain concerns and benefits of different NSAID’s. Non-acetylated salicylates. Does anybody here use non-acetylated salicylates? Do use non-acetylated salicylates. They have some significant benefits. Since they are non-acetylated they still have analgesic properties.

There are different avenues we can go for relief of pain. Certainly instructing people on rest periods. Sometimes fatigue is a significant aspect of their RA and sometimes they need to be instructed to take these brief hiatuses, either a nap or just a rest period. Heat can be helpful. The old thing people used to use a lot, the paraffin wax treatments to give that deep heat because it helped relieve the stiffness. Exercise, certainly doing range of motion exercises is okay. Strengthening exercises should be reserved for patients when they are inactive.

When we want to try and control disease, again we’ve talked about the medications for the control of pain. For control of disease we can use some of the same medications, the salicylates and the non-steroidals. They tend to be adequate only for a small percentage of patients and usually those with fairly mild disease. The SAARD’s , slow acting agent of rheumatic disease. Different people have said that we are not really sure that these disease-modifying agents are really disease modifying, so let’s just call them slow-acting agents. That’s where the SAARD came from. Certainly the disease-modifying agents or the SAARD’s become a significant factor in helping to try and control the disease.

Steroids. Steroids do a great job in making people feel better. They make people feel so well, they don’t ever want to give them up. The biggest challenge you have is people - once they get those pills in their hands - they adjust them and do whatever the heck they want with them without even talking with you. Unfortunately it becomes a real problem trying to get the steroids decreased or discontinued. An important thing; steroids do not alter the course of the joint disease. They may feel great but the destructive process continues. We all know about the toxicities of steroids. Dr. Hollander, who is sometimes considered the father of rheumatology, was at University of Pennsylvania and he was one of the initial people to use steroids when corticosteroids were first discovered, and he started saying, "Gosh, this is like a wonderful cure for RA." Well, we learned a lot about steroid toxicity. It’s still a problem today. There’s a lot of other sort of either novel, or outdated, or other treatments people have done. Total nodal irradiation, plasmapheresis, lymphopheresis, etc. which have limited benefit or unproven benefit and certainly can be toxic and expensive. Physical therapy can play a role. Just like the exercises we talked about before.

Surgery certainly has it’s role. Surgery, most commonly we do synovectomies, joint replacement surgery, occasionally the joint fusion, particular things like wrists do real well with that. Tendon repair as a nerve entrapment releases. So all of these things are going on at the same time.

Let’s talk about some of these slow-acting agents. Gold salts, once the mainstay of treatment for RA, can be given both intramuscularly and orally. Most commonly they are given intramuscularly because frankly they are more effective intramuscularly. The studies surely show that intramuscular is more effective, but it also seems to be more toxic. It causes rashes, stomatitis, proteinuria, leukopenia, people need very frequent monitoring of CBC’s, urinalyses, to look for this kind of involvement. Oral gold salts cause more of a diarrhea problem.

Anti-malarials, hydroxychloroquine, I happen to be a fan of hydroxychloroquine particularly in milder disease. A certain percentage of people do really well with hydroxychloroquine or Plaquenil. Rashes are occasionally a problem. Rashes occur in maybe 1% of patients, or 2% of patients. They can be pretty ugly rashes.

D-penicillamine. I think I’ve written one prescription for D-penicillamine in my life. It was a patient who was already on D-penicillamine when I met her. D-penicillamine has a lot of toxicities and more rheumatologist don't use it anymore, although occasionally you can see it. I wouldn’t recommend starting people on this therapy unless we have no other alternatives.

Methotrexate. Methotrexate is obviously the mainstay of treatment in RA at this point. Most rheumatologists now use this as a first line therapy. It does have some toxicities. Most rheumatologists are very comfortable with these toxicities. The biggest concern has always been liver disease and the longer we’ve had experience with methotrexate in RA the less we are concerned with liver disease. The initial studies in arthritis with methotrexate were in psoriatic arthritis and they tend to be the patients that developed a lot of liver problems, and we just haven’t seen it as much in RA patients. That doesn’t mean we ignore liver disease. We just are less concerned.

Other medications: azathioprine, Imuran. Imuran is still used in a significant percentage of patients. I’m trying to avoid it because of some of the theoretical concerns and real concerns. There is probably, almost undoubtedly, and increased risk of malignancies with azathioprine. It also has hematologic toxicities, concerns of infection, etc. The doses tend to vary between 50-150 mg and often we’ll use the WBC as a measure of whether we can push the dose any higher. If the white count is still 6,000 we can probably get by with higher doses. I’ve used it up to about 225 mg on a daily basis. Cyclophosphamide, I don’t know very many people who use cyclophosphamide.

We’ve gone through a little evolution of RA treatment that sort of got you where we are now. When you look back at the 1960’s the reason why they weren’t very aggressive was they did a lot of studies. And they looked at people with RA and they said, "Gosh, this disease isn’t all that bad. People tend to do pretty well, most patients don’t even have disease 3-5 years later." Then you go back and you find out how in the world they did these studies. What they did is they did phone surveys and they called people up and said, "Do you have rheumatoid arthritis?" "Well, sure. Yeah, I’ve got rheumatoid arthritis." Then they’d reevaluate those patients by phone contact 3-5 years later.

We know there is increased mortality predicted by difficulties with activities of daily living, increased walk time. And educational level, for reasons that are not well understood, is correlated with mortality. People with lower education levels do worse. So the pyramid approach had its problems.

There’s a lot of developments occurring that’s going to change the face of the way we are even treating people now, but some of the things we have recognized. Disease-modifying agents are not necessarily disease modifying. People are still progressing. We either are not hitting them early enough or these medications still aren’t doing the job to control the disease. We are still seeing significant radiographic disease as early as a couple of years. We are still seeing that methotrexate is being used earlier and earlier and earlier, and more widespread. Most rheumatologists now use methotrexate first and ask questions later. What they do is use methotrexate and those people who don’t do well with methotrexate - either they don’t tolerate it - they will go ahead and try combinations or other drugs for the methotrexate failures. Do I start every single person with rheumatoid arthritis on methotrexate? No. But it’s getting more and more that way. There are certain other institutions where they are trying very aggressive treatment. There’s a group in Seattle that their approach was, as soon as someone came in with a diagnosis of RA they put them on quadruple therapy; prednisone, methotrexate, auranofin, hydroxychloroquine. And guess what? If you are not completely better in three months we are putting you on azathioprine. It sounds pretty aggressive but their idea is they want to try and nip this thing in the bud so it doesn’t cause damage. We don’t know yet. We don’t have enough history here. Remember, we need longer history before most of us are going to jump on the bandwagon and put people on six drugs at the same time, to see if it actually works. But these are the kind of things that are being tried in this country right now, to try and control this disease, to try and improve people’s lives.