""Anyone can hold the helm when the sea is calm."
-- Publilius Syrus
Early rheumatoid arthritis: what is the best treatment approach?
Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder characterized by joint inflammation and joint destruction.
If left untreated or poorly treated, RA is associated with progressive functional disability, significant morbidity, and even increased mortality.
In recent years, the addition of biologic therapies to conventional disease-modifying anti-rheumatic drug (DMARD) treatment has improved the prognosis of RA, with superior symptom improvement as well as improved results on x-ray progression.
The idea that early RA may be better controlled if treated earlier in the disease course has been supported by animal models.
Early RA is now defined as RA of as little as 3 months to as long as 1 year’s duration.
Patients with early RA exhibit a typical picture in their joints when the inflamed tissue is examined in the laboratory indicating that there is a narrow "therapeutic window of opportunity" in which to put the disease into remission.
Studies have indicated that early treatment with combination of DMARDs has been shown to be superior to single DMARDS.
More recent trials have shown the addition of biologics to DMARD therapy also exhibits positive outcomes.
Clinical trials of the 5 currently FDA-approved tumor necrosis factor (TNF) inhibitors – etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), golimumab (Simponi), and certolizumab (Cimzia) -- have been conducted in patients with early RA. In these studies, the comparison drug has been methotrexate, the typical standard of care.
The Etanercept in Early Rheumatoid Arthritis (ERA) trial compared Enbrel at 2 different doses with methotrexate, all as single agents. Although the clinical responses to all agents were good, patients receiving Enbrel alone also had a more rapid clinical response. In addition, x-ray measurements showed the superiority of TNF inhibition compared with methotrexate alone.
The Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) trial evaluated the efficacy of Remicade at 2 different doses, given in combination with methotrexate vs methotrexate alone in patients with early RA who had never received methotrexate.
Patients treated with the combination had more rapid and greater clinical improvement and better radiographic outcomes.
The PREMIER study evaluated the efficacy of combination therapy with adalimumab (Humira) plus methotrexate compared with each therapy alone. In this trial, clinical responses with methotrexate or with Humira were comparable, but the greatest responses were achieved with combination therapy. With regard to joint damage, Humira alone did better than methotrexate alone, but the best x-ray results were seen with the combination.
Similar types of studies have been conducted with the two newest entrants into the TNF inhibitor market, Simponi and Cimzia.
Results from all of these studies clearly showed the potential benefit of TNF blockers in early RA. Also, it was clear that the combination of TNF blockers with methotrexate was extremely effective in regard to signs and symptoms of disease, improvements in functional status, and inhibition of x-ray damage.
Safety is an important consideration when treating RA patients with any therapy that affects the immune system. Although much is known about the potential safety issues with biologic agents, there is little information in regard to the safety of biologics in early RA. The risk-benefit ratio will depend on continued monitoring and analysis of safety information. It must be emphasized that RA is not a benign disease, causing a significant mortality risk on the order of death occurring 10-15 years earlier in patients with RA versus people without RA.
Wei's World July 2009
Stood up again!!
Ever been stood up? You know… you have an appointment, generally a date, and the person doesn’t show up? Boy… does it hurt. The first time was in college. And I have to admit, the girl probably did the right thing because I was a total dork.
The second two times were when I was a resident physician in Ann Arbor, Michigan at the University of Michigan.
You know how it is, or maybe you don’t. For a guy this is the drill. You’re anticipating and wondering what it will be like to go out with somebody new. You’re excited… probably nervous too. The day comes and you shower, use deodorant, put on some nice clothes, check yourself out in the mirror, pose a little, hop in the car and go out to meet the girl.
Now when the girl doesn’t show up, you think, well maybe she’s just late, maybe she got lost, is this the right place, the right time, the right date? Then after a while it dawns on you. You’ve been stood up!
It just happened to me again. I was supposed to be on TV to talk about fibromyalgia. The film crew from NBC was supposed to show up at 8:30 AM sharp and be done by about 9:00. So eight-thirty comes and goes. Then nine o’clock. And we make some calls. Well, it turns out that another more newsworthy event took place and the crew went to film that. I don’t remember what it was but I think either Miss Maryland was chowing down on a burrito from the dollar menu on the Route 40 McDonald’s or some prize pony escaped on the highway... or something to that effect.
Did I get flashbacks to my earlier young manhood? Sure, I did. But, let’s be philosophical about it. I had many more dates that showed up than didn’t. And another TV opportunity will come along sometime and maybe the crew will show up next time. That would be nice.
As I mentioned in the last newsletter, I'm working on a new project about PRP/stem cells/prolotherapy. If you have any burning questions you'd like to see answered about these topics, please shoot me an email at firstname.lastname@example.org. Thanks!
Visit my blog at www.nathanwei.wordpress.com. I try to update it at least weekly and sometimes more often. You can also follow me on Twitter. I'm "thearthritisdoc"