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The following is a transcribed speech that Arthur Kunath, MD, of Kunath, Burte & Temming, a single-specialty group in Crestview Hills, Ky., recently gave at an Arthritis Foundation Ohio River Valley Chapter meeting in Cincinnati.
Things are very different for the RA patient today compared to the turn of the century, because there has been a revolution in the understanding of the disease and the ability to treat the disease.
Just from a diagnostic point of view, we're able to assess damage and make a more accurate diagnosis early on because of the blood tests and X-rays we can obtain today. In 1900, they had just started using X-rays, but they didn't have the blood tests.
In 1900, a physician could only treat RA patients with pain medicine, morphine and/or aspirin. That was really about all they had. It wasn't until the 1920s that some of the more aggressive physicians began using gold salt compounds for the treatment of RA. Gold salt therapy was actually discovered serendipitously by doing a study on tuberculosis patients.
While the gold salts didn't help the tuberculosis patients, it did help the people with tuberculosis and RA. We picked that up in the mid-'20s. But even at that time, we only had aspirin and the occasional gold shots.
Around this time, the only way they could treat JRA was to put the child's arms and legs in casts until all their major joints fused together. They couldn't move, so their pain diminished. That was a pretty barbaric way of treating the patient, but some physicians didn't feel like they had a choice.
There weren't really any big discoveries until the '40s when Philip Showalter Hench at the Mayo Clinic discovered the cortico steroids. He entered this into the clinical practice in 1949, when his reports came out.
What's interesting is that after Hench published his study, he went to New York City and showed films of a patient of his that could barely walk up or down two stairs because of their advanced case of RA. He then showed a film of the same patient after he had treated them with the steroid. The patient walked up and down the stairs easily, without any pain.
So, for a short amount of time, we actually thought this was the cure for RA. But after a few years of treatment, we found out that it was a very potent, powerful drug with a number of side effects.
Over the '50s and '60s, we really spent that time learning how to use steroids appropriately. It was still a great medicine. In fact, we still use it today, but it was a revolutionary medicine that needed to be carefully applied in clinical practice.
The non-steroidal and non-Aspirin anti-inflammatories started in the 1960s. Then there was the introduction of Indocin, Motrin, Naprosyn and a whole host of other anti-inflammatories. That was helpful for the control of symptoms. Symptomatic control was about all we could offer the patients at that time.
Unfortunately, many of the patients at this point in time still continued to experience deterioration, and some of them had bad reactions to the gold salt therapy's toxicity.
In the '70s, the Cleveland Clinic began to use oral and injectable Methotrexate. This slowly gained popularity, so that by the middle '80s, it had been demonstrated in a number of important studies as more affective than gold, less toxic than gold, better tolerated than gold and it helped a significant number of patients.
At this point, we had a good 30 percent to 40 percent of patients with rheumatoid arthritis that responded well on just the Methotrexate. But even with all that, we had 60 percent to 70 percent of these patients on an anti-inflammatory, on steroids and on Methotrexate who still advanced and developed deformities.
A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study.
Arthritis Research Centre of Canada and University of British Columbia, Vancouver, British Columbia, Canada.
OBJECTIVE: To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX). METHODS: A randomized, double-blind, double-observer, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >/=12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent-to-treat strategy. RESULTS: Sixty-one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo (chi(2) = 6.04, P = 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P = 0.016). Twenty-six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P = 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P = 0.011). From both clinical and cost-effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P = 0.022) due to loss to followup, adverse events, or lack of efficacy. CONCLUSION: In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold-related adverse events led to discontinuation in only 11% of the gold group over 48 weeks.
Prescriber Update No.18:4-12
Dr Andrew Harrison, Rheumatologist, Senior Lecturer in Medicine,
Wellington School of Medicine, New Zealand
Rheumatologists and general practitioners have a shared responsibility
for the care of rheumatoid arthritis (RA) patients taking
disease-modifying anti-rheumatic drugs (DMARDs). Assessment by a
rheumatologist is recommended within 3 months of the patient
developing symptoms of RA. As DMARDs can be toxic, a risk/benefit
analysis should be undertaken prior to commencing therapy. A
meta-analysis has shown methotrexate and sulphasalazine have
relatively high efficacy and low toxicity, anti-malarials have
moderate efficacy and low toxicity, and intramuscular gold has
moderate efficacy but relatively high toxicity. Current practice
favours the use of methotrexate, sulphasalazine and hydroxychloroquine
(given as monotherapy or in combination) over other agents such as d-penicillamine,
azathioprine and gold salts.
Methotrexate: Adverse effects - nausea & stomatitis (common), bone
marrow suppression, liver disease & interstitial pneumonitis (rarer
but potentially serious). Monitoring – baseline CXR, CBC, LFTs and
serum creatinine, repeat CBC, LFTs and serum creatinine every 4-8
weeks.
Sulphasalazine: Adverse effects - nausea, skin rash, Stevens-Johnson
syndrome, neutropenia (2%) & aplastic anaemia. Monitoring - baseline
CBC & LFTs. Repeat CBC every 2-4 weeks for first three months, then
every three months.
Hydroxychloroquine: Adverse effects - nausea, rash, bone marrow
suppression, agranulocytosis, aplastic anaemia, and corneal and
retinal damage at higher doses. Monitoring - baseline serum creatine.
Routine review by an opthalmologist every 6-12 months in those taking
> 6.5mg/kg/day and/or the elderly, those with renal impairment, or
duration of treatment greater than 10 years.
HOW WELL DOES BALENOTHERAPY (BATHING IN WARM WATER) WORK TO TREAT RHEUMATOID ARTHRITIS AND HOW SAFE IS IT?
To answer this question, scientists analysed 6 studies. The studies tested over 350 people who had rheumatoid arthritis. People continued to take their medications but either bathed in warm water, had mudpacks, did water or land exercises or did nothing differently for 2 to 4 weeks. Not all studies were of high quality but this Cochrane Review provides the best evidence about balneotherapy that we have today.
What is balneotherapy and how might it
help rheumatoid arthritis?
Rheumatoid arthritis is a disease in which the body's immune system
attacks its own healthy tissues. The attack happens mostly in the
joints of the feet and hands and causes redness, pain, swelling and
heat around the joint. Balneotherapy, also called spa therapy, means
bathing in warm water at about 36 degrees celcius with minerals added
to it or naturally occurring. It is thought that balneotherapy
decreases gravity on painful joints to soothe pain, relieve muscle
spasms and improve muscle strength and function.
How well does it work?
In most studies, people were asked how they felt 3 months after the 2
to 4 week treatment.
One low quality study found that more people had improved morning stiffness, walk time and ability to do daily activities with dead sea salt and/or sulphur baths than with no balneotherapy. Two other low quality studies showed conflicting results for dead sea salt or mineral baths, while a higher quality study found that radon-carbon dioxin baths decreased pain.
One low quality study found that more people had improved morning stiffness, walk time and ability to function with sulphur baths than with mudpacks or no balneotherapy. A high quality study found that more people had improved morning stiffness, pain and overall with tap water baths than with land or water exercises or relaxation.
How safe is it?
The studies did not test for side effects or safety of balneotherapy.
What is the bottom line?
There is "silver" level evidence that balneotherapy or bathing in warm
water may improve symptoms of rheumatoid arthritis. But most studies
are of poor quality and therefore it cannot be concluded that
balneotherapy works. It is also not clear if the effect of
balneotherapy depends on water temperature and the addition of
minerals to the water.
It is also important to consider that the change of environment, the 'spa-scenery', the decrease in activity, the company of other people with rheumatoid arthritis and relaxation while at balneotherapy may be the reason for improved symptoms and may not be due to the "water".
Finally, at the end of the century, a series of compounds – known as the anti-tumor necrosis factor compounds – was discovered, and that had a revolutionary impact on rheumatoid arthritis. We could show significant symptomatic relief, halt progression of the disease and even prevent destruction, erosion and deformities in a significant number of patients. These drugs include Enbrel, Remicade and Humira.
In just the past few months, we've added two new medications: Orencia, which works on the T-cell interaction, and Rituxin, which helps RA patients quite significantly because it interferes with B-cells. So, we really have a number of drugs that are able to give us a better handle on RA.
The classic way of imaging these patients is plain radiographs of hands, wrists and feet. We look at those to see if there is any joint space narrowing or erosion. But over time, we discovered that this doesn't always distinguish enough. The X-ray response to this disease is often delayed, so we have started to think of ways we could get a head start and detect RA earlier.
We're now to a point where we think MRI may distinguish people who have early inflammation in the joints and erosive or destructive changes. These things can be seen earlier on MRI than plain films, at a stage where we can intervene and prevent progression.
For the small joints, we're starting to use ultrasound. Especially in the hands, this helps us to distinguish how much of an inflammatory burden the patient may have. So, those are the leading modalities that are being investigated. They aren't definitive yet, but I think there will be a place for both those modalities in the future when attempting to make an earlier and more accurate diagnosis.
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