If left untreated or poorly treated, RA is associated with progressive functional disability, significant morbidity, and even increased mortality. What this means is that RA is not just a disease associated with painful stiff joints but a disease which can lead to inability to perform even the simplest daily taks... as well as significantly shortening lifespan. This reduction in years lived can range anywehre from 3-7 years in mild disease and 10-15 years with more serious disease.
In recent years, the addition of biologic therapies to standard disease-modifying anti-rheumatic drug (DMARD) treatment has improved the prognosis of RA, with better symptom improvement as well as slowing of x-ray progression.
The idea that early RA may be better controlled if treated earlier in the disease course has been supported by by animal models as well as human studies.
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 combinations 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 3 currently FDA-approved tumor necrosis factor (TNF) inhibitors ? etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira) -- have been conducted in patients with early RA. In these studies, the comparison drug has between methotrexate, the typical standard of care.
One example is the the Etanercept in Early Rheumatoid Arthritis (ERA) trial which compared Enbrel at 2 different doses with methotrexate, all as single drugs. Although the clinical responses to all three drugs were good, patients receiving Enbrel alone also had a more rapid clinical response. In addition, x-rays demonstrated the superiority of Enbrel in slowing x-ray progression compared with methotrexate alone.
The Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) trial compared 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 faster and greater clinical improvement and better x-ray outcomes.
The PREMIER study evaluated the effectiveness of combination therapy with adalimumab (Humira) plus methotrexate in comparison with each treatment alone. In this trial, clinical responses with methotrexate or with Humira were similar, but the best responses were aobtained with combination therapy. In regards to joint damage, Humira alone did better than methotrexate alone, but the best x-ray results were seen with the combination.
Results from all of these studies clearly showed the 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 function, and slowing of x-ray damage.
Another study evaluating the best approach to early RA was the BeSt trial. BeSt was a randomized clinical trial of 508 patients with early RA, defined as patients with less than 2 years of disease conducted in Europe.
Patients were randomized to receive 1 of 4 different treatment strategies including methotrexate alone, methotrexate with another DMARD, methotrexate with sulfasalazine, and methotrexate with Remicade.
After more than 4 years of follow-up, nearly 50% of patients in each of the 4 groups of the BeSt study went into remission. Regardless of the type of initial treatment, a strategy of frequent evaluation of disease activity and change of therapy to achieve low disease activity, ie. "tight control" ? led to a superior and sustained benefit for up to 4 years.
Both practitioners and patients have expressed concerns about the long-term safety of using biologic medicines which alter immune function. Although much is known about the safety issues with biologic agents in general, there is little information in regard to the safety of biologics in early RA. What happens when a young person receives biologic therapy and is kep on it for 20-30 years? We really don't know yet. The risk-benefit ratio will depend on continued close monitoring and analysis of safety information as it becomes available.
What we do know is the dramatic improvement in quality of life and slowing of progression of disease that is experienced by patients treated with these agents.
RA is one of the leading causes of disability.
And, because it is a systemic disease it can cause significant damage to other organ systems besides the joints including the eyes, heart, lungs, and blood.
The prognosis for this condition has improved dramatically in recent years because of the advent of new drug therapies that make it possible to put RA into complete remission. Unfortunately, aggressive therapy depends most on making a correct diagnosis early on so that appropriate medications can be instituted as soon as possible.
A significant barrier to this problem occurs at the primary care level. Patients with rheumatoid arthritis are often not diagnosed early enough, not sent to rheumatologists quickly enough, and a new study finds that sometimes the diagnosis appended to the patient by the primary care physician may be erroneous.
In this recent article, researchers looked at the way rheumatoid arthritis is diagnosed by analyzing the administrative databases used by physicians in Quebec.
The authors of the paper, published in Arthritis & Rheumatism (Feldman DE, et al Arthritis Rheum. 2007; 57: 1419-25), reported that general practitioners diagnosed 79% of the 10,001 rheumatoid arthritis cases but only 27% of patients then saw a rheumatologist. Roughly, half of these patients were seen in the first three months following the initial diagnosis and then of these remaining patients, only 17% actually were confirmed with the diagnosis of rheumatoid arthritis.
Senior author, Annelies Boonen commented that, "The low referral rates of cases with suspected rheumatoid arthritis to rheumatologists is worrisome, especially when considering the discrepancy in diagnoses between the initial diagnosis by the non-rheumatologists and the following diagnosis by the rheumatologists."
The authors recommended further research to confirm the findings and explore the wider implications of the study. They went on to say, ?If we really feel the window of opportunity for treatment of rheumatoid arthritis exists, rheumatologists should increase their efforts to raise diagnostic capabilities of first-line physicians towards early diagnosis and referral of suspected patients with rheumatoid arthritis".
The study points out several significant problems when it comes to the early diagnosis of rheumatoid arthritis. First, rheumatology training for primary care physicians is not adequate. In the United States, many primary care residency programs spend little time on educating their residents on rheumatic disorders. Therefore, the diagnostic capabilities of primary care physicians when it comes to rheumatic disease is less than it should be. This is not the fault of the primary care physician; rather, it is a flaw in the educational process. And this flaw extends to care extender programs such as those for nurse practitioners as well as those for physicians? assistants.
Second, the magnitude of the problem- early RA- has not been impressed enough on primary care providers. Early RA is essentially a medical emergency in that there is a small window of opportunity that exists in which permanent damage can either be slowed or avoided by institution of aggressive therapy. RA can be put into remission but timing is critical.
Third, there are other rheumatic diseases that can look like RA and the treatment is very different. Proper diagnosis is key to correct treatment. Just as important as making the diagnosis of RA and instituting proper aggressive therapy is not applying anti-RA treatment to patients who do not have RA.
Fourth, the early diagnosis of RA is often a difficult one to make and patients with suspected RA should be referred as soon as possible to a rheumatologist.
Nathan Wei has sinced written about articles on various topics from Arthritis Pain, Health and Arthritis Signs. Nathan Wei, MD FACP FACR is a rheumatologist and Director of the Arthritis and Osteoporosis Center of Maryland. He is a Clinical Assistant Professor of Medicine at the University of Maryland School of Medicine. For more info:. Nathan Wei's top article generates over 550000 views. to your Favourites.