Albinoblackbear notes in a post on her blog, Asystole is the Most Stable Rhythm (no
kidding?), that doctors frequently have no idea why some drugs for rheumatoid arthritis work. Or don’t work. ABB is a Canadian nurse who’s in med school in Ireland at the moment; the future doctor offers a quote from a 2009 textbook on pharmacology and is charmed by its honesty. Go take a look.
It’s no surprise to me that doctors and medical researchers are basically clueless about these drugs and how they work. They’re mystified by the disease itself, after all. They know that it’s an autoimmune disease in which a person’s antibodies attack her own tissues, but they don’t really know why. Nor do they know why it affects three times as many women as men; or why one person will be quickly disabled by it and another not. RA is an enigma.
Still, it seems that each year brings them, and us, a little closer to the answer. When I was diagnosed with RA, my doctor first put me on increased dosages of aspirin. Then he added NSAIDs. Over the years, we tried plaquenil (originally a drug used to fight malaria) and oral gold. None of them had any effect on my symptoms. I’ve since learned that methotrexate was beginning to be used frequently by 1987; that was never offered to me, though. I think perhaps my doctor, who was an internist and not well versed in treating RA, may not have known about it. Or perhaps he did, but the U.S. Army in Europe’s medical system didn’t have it in their formulary.
No matter. I discovered two summers ago, when my rheumatologist started me on it, that I couldn’t tolerate MTX. It made me feel like I was on the brink of death. After three months during which the only affect it had was to make me feel horrible, he replaced it with Arava. I’m still taking it; the only side-effect I’ve noticed is that it’s making me slowly lose my hair. As long as it doesn’t all fall out all at once, leaving me bald, I can deal with it.
And now, there are biological drugs which help some people with RA a great deal. “Some” is the operative word, however. They help some people for a while, then stop, too. Or they don’t help at all. Or they help as long as the person is taking methotrexate too. Or. Or. Or.
I get frustrated when the meds I take don’t seem to have much, if any, effect. But I’m beginning to understand that my doctors are just as frustrated as I am. And just as mystified. Oddly, that makes me feel a little better about it.
RheumaBlog 
Interestingly, I work in an immunology based lab, and while it does not deal with RA, it does give some insights into the general “well we don’t know how or why it works but it does” moments. In fact, on of the projects I was given when I first joined this lab was a “figure out why this works” task. In transplant, specifically bone marrow transplant in my case, performing extracoporeal photopheresis (aka pull blood out a patient, separate out the white blood cells, treat them with a light sensitizing drug, treat them with UV which causes them to die, reinfuse dying white blood cells back to patient) works really well at treating graft versus host disease (where the bone marrow graft does not see the recipients body as self and attacks it, much like an autoimmune disease save for the fact that it isn’t autoimmune, just a transplanted immune system). Now, I have no idea who came up with this idea, but it worked, reducing graft versus host disease in patients that this disease was trying to kill them. The murine model for this treatment process came after the treatment was well in place and I can tell you from personal experience, we still don’t know exactly why it works, though we do have a few key parts.
As to the why more females part, one theory running around the immunology world is that because women have babies, they must be more tolerant to non-self (ie babies in the womb) but this same mechanism can then also go haywire, become less tolerant, and attack self instead. In essence, because women can have babies, their immune systems must behave different from time to time and this ability somehow also may contribute to autoimmunity.
My biggest piece of advice to you and anyone else out there with a disease that we don’t understand is become part of a clinical trial or a study. You don’t have to be part of one where your medicine is changed or you try new treatments (though sometimes they really do help) but simply by becoming part of a study, you add to the pool of knowledge. You help us scientists figure out the whys and develop the better treatments. We do this for you, but we cannot do it without you. Locked inside of you are all our answers, we just have to figure out how to unlock all of those answers.
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Wren, I just wanted to thank you so much for all of your recent comments on my blog. As I have been busy making new choices in my RA plan, I have been comforted to go back and reread your comments. They always make me feel good inside. You have a true gift and I am so glad to have found you! Cathy
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I agree, RA is definately still a mystery. It was not until the 1940s that researchers discovered that RA had to do with a malfunction of the immune system. That was also about the time when the rheumatoid factor was discovered. Cortisone was first med prescribed for RA in 1949 and then in 1955- prednisone was the lead drug.
Yes, we have a along ways to go. The answers still aren’t there but there is a lot of research and money being invested so we are getting closer to those answers. Perhaps having those answers might lead to earlier diagnosis and much better treatments.
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