Identifying RA Before it Starts

Rheumatoid arthritis can be diagnosed before the damage begins

/ Author:  / Reviewed by: Joseph V. Madia, MD

Rheumatoid arthritis can cause joint deformities and disability, but what if it could be prevented? Doctors may have found a way to identify the disease before it begins and actually stop it from developing.

Subtle inflammation and joint changes that occur before there is actual damage can now be detected through MRI in clinical trials, and drug therapy may be able to dramatically slow or prevent the development of rheumatoid arthritis.

Treatment with biologic agent golimumab (Simponi) could be a big step forward for those who suffer from the incurable autoimmune disease, which is characterized by inflammatory arthritis, Dr. Philip G. Conaghan, a professor of musculoskeletal medicine at the University of Leeds in England, found in a recent study published in the Annals of the Rheumatic Diseases.

Imaging rheumatoid arthritis

Currently x-rays or radiographs are traditionally used for imaging rheumatoid arthritis patients. Ultrasounds also can be used to measure inflammation, but there is no central reading as with MRIs and it requires correction for multiple readers, making it a less responsive tool.

"These (x-rays) are great because they're feasible; they're quick; they're cheap, but they only evaluate damage, which is the end result," said Dr. Conaghan. "MRIs measure inflammation, which leads to damage, as well as damage."

This includes being able to view inflammatory swelling and lesions in the bones, also called bone edema. But MRIs are not yet being used in a clinical setting until it can be determined how they would be most useful.

"In the study we used (MRI) for the outcome, but we are still lacking good clinical algorithms to use it in clinical practice," Dr. Conaghan said.

But once the use of MRIs has been hammered out, it could be a tool that could benefit numerous patients in a clinical setting. Dr. Conaghan said MRIs would be useful for diagnosing, and also monitoring patients with more severe forms of the disease. The imaging tool also would allow for tighter control over inflammation.

"It's sensitivity detects inflammation, and the imaging probably should be used even where we think the patient is doing well," Dr. Conaghan said.

Clinical results

Dr. Conaghan and his colleagues subanalyzed the randomized GO-FORWARD trial, which involved 444 patients with a low degree of active rheumatoid arthritis despite treatment with methotrexate (MTX).

The patients were divided into groups and received either MTX plus a placebo, 100 milligrams of golimumab plus a placebo, 50 milligrams of golimumab plus MTX, or 100 milligrams of golimumab plus MTX through a monthly injection.

Of those patients, 240 patients received MRIs of their dominant wrist and metacarpophalangeal joints, the large joints at the end of the fingers that aid individuals in grasping objects, at the beginning of the study and also at 12 weeks, 24 weeks, 52 weeks and 104 weeks. The images were checked for inflammation, bone swelling and bone erosion.

At the 16-week mark, patients from the first three groups who who did not experience an improvement of at least 20 percent in tenderness and swelling of their joints entered "double-blind early escape," where they were moved to the next group, in most cases receiving an increased dose of medication.

Researchers found significant improvements in inflammation and bone swelling in the groups that took both MTX and golimumab as compared to those who took MTX and a placebo at both 12 weeks and 24 weeks.

Less than 10 percent of all patients experienced a substantial degree of erosive progression, which meant that researchers were unable to evaluate golimumab's effect on bone erosion.

However, in the study, Dr. Conaghan noted: "The fact that only minimal progression of bone erosion was observed even with MRI confirms that these patients did indeed have minimal progression in structural damage during the 6-month study period."

Dr. Conaghan mentioned that though golimumab was used in the study, other drugs such as adalimumab (Humira) and other biologic agents likely also would offer similar joint-preserving benefits.

RA changes

With research advances rheumatoid arthritis has become more manageable for patients, and it's already possible to force the disease into remission before irreparable joint damage.

"Rheumatoid arthritis management really has been revolutionized in the last 15 to 20 years," Dr. Conaghan said. "There are a number of concepts that have come along, and we are treating earlier. Secondly, we've used existing drugs better and had better outcomes. Then there's this new class of drugs -- the biologic therapies, which are very expensive but have made a major impact."

One of the keys to early detection is a simple blood test to check for antibodies that could predict who will develop rheumatoid arthritis. Figuring out who to test to ensure it is captured early though is still tricky.

"We've gotten so good at treating it so we are trying to get people earlier and earlier. People who just have vague aches and pains are getting an antibody screen," Dr. Conaghan said. "What we've got now are very effective therapies for people with the disease, and growing literature on very early inflammation arthritis and trying to detect just positive antibodies before there are symptoms. We could try to prevent them from getting arthritis,"

Dr. Conaghan's research was funded by Centocor Research and Development and the Schering Plough Research Institute, and investigators disclosed receiving consulting fees and grants from companies including Centocor, Schering Plough, Pfizer, AstraZeneca, Bristol-Myers Squibb, Merck, Novartis, Roche and Wyeth.

"I think we are getting better at treating early, but it would be better if we can prevent the disease," said Dr. Conaghan. "But we may need different drugs to prevent the disease."

Review Date: 
October 29, 2011