Arthritis: A Joint Effort

The Game Plan

Researchers at the four to six clinical centers taking part in the Osteoarthritis Initiative will follow study participants for four to five years while providing them with "the highest standards of care," says planning group member Thasia Woodworth, who helps direct arthritis research at Pfizer Global Research and Development in New London, Conn.

The government and the drug firms will split the $8 million-to-$10 million yearly cost of the study.

Medical information collected during the study, including assessments of patient pain and function, and X-rays and magnetic resonance imaging (MRI) of joints, will be freely available to researchers worldwide. Blood and urine samples and DNA will be available to those who receive permission from an independent review committee.

Scientists will use these resources to identify so-called biological markers of disease and disease progression. These markers may include features of joint structure, such as bone spurs or cartilage thickness or volume, that show up on an X-ray or MRI, and substances in the blood or urine. They will also look for genetic factors that affect a person's risk of disease development or progression. A 1996 study indicated that genetic factors account for at least half of all cases of osteoarthritis in the hands and hips, and a smaller percentage in the knees.

At present, the most widely used method for monitoring disease progression in the knee is an X-ray measurement of the distance between bones in the joint -- which is thought to reflect the amount of cartilage present. (Unlike MRIs, X-rays do not show cartilage.) But some experts say this "joint-space width" is not a sensitive or reliable indicator of progression because some people have narrow joint space and little or no pain or loss of function, while others have pain and impaired function but no apparent joint-space deficit. Joint-space width also varies depending on exactly how the X-ray is taken.

The lack of sensitive disease markers means that clinical trials to test the safety and effectiveness of new drugs for osteoarthritis take at least two to three years and require large numbers of patients. This makes the testing very costly. Organizers of the initiative hope that identifying better markers will streamline clinical trials and spur development of drugs that modify the course of disease.

"Without reliable biomarkers, we will have a very hard time making decisions about taking drugs forward into the long development process that's likely," says Woodworth.

Meanwhile, some companies, including Pfizer, are moving ahead with development and testing of drugs that would have a huge and ready market.

"We can't stop trying to develop drugs for osteoarthritis, waiting for the results" of the initiative, says Woodworth. The hope, she says, is that the results will support methods of measuring disease progression that companies are already using to test next-generation drugs.

Moving Forward

Jim Jensen and his fellow boomers can't afford to sit idly waiting for a possible breakthrough either. As the search for better disease treatment continues, Jensen realizes some of the responsibility for maintaining his mobility and lessening the impact of the disease falls to him. Studies show that losing excess weight, exercising, learning about the disease and its treatment and taking an active role in its management all help reduce pain and maintain function.