Magazine article Drug Topics

ACR Focuses on New and Emerging Arthritis Drugs

Magazine article Drug Topics

ACR Focuses on New and Emerging Arthritis Drugs

Article excerpt

New drug therapies for rheumatoid arthritis (RA) were the hot topic at the recent American College of Rheumatology (ACR) annual meeting, held recently in Philadelphia. Amgen reported on five studies that found that its investigational agent, anakinra or interleukin-1 receptor antagonist (IL-1ra), may accelerate reduction of joint damage progression and, thus, improve the quality of life for RA patients.

In one double-blind, multicenter trial, 472 patients randomly received 30 mg, 75 mg, or 150 mg daily of anakinra or placebo. After six months, the placebo patients were randomly switched to treatment with one of the anakinra doses. They were then evaluated by X-rays using a state-of-- the-art assessment tool that measures joint destruction based on erosive damage and joint space narrowing of the hand and wrist.

"Anakinra-treated patients showed nearly twice the rate of reduction in joint destruction as the placebo group," said lead researcher Barry Bresnihan, M.D., professor of rheumatology, University College, Dublin. "Six months later [at 75-mg and 150-- mg doses], their improvement accelerated still more. Other data showed that the longer they were on therapy, the better they functioned. These findings suggest anakinra may cumulatively slow joint damage."

IL-1 is a cytokine and a natural mediator of joint inflammation and destruction. When IL-1 binds to its receptor, the immune system starts a chemical reaction to fight off infections and decrease tissue injury and cell death. In people with RA, however, activation of the immune system persists, leading to a flood of IL-1 [and other] proteins that induce inflammation and damage, explained Bresnihan. "Anakinra is a recombinant form of natural IL-1Ra that binds to IL-1 receptors and blocks the deleterious action of excess IL-1 that RA patients produce," he said.

Long-term help

A research team from University College, London, claimed that its experimental RA therapy, which targets out of-control B-lymphocytes, shows remarkable potential in a pilot study, even allowing some bedridden patients to return to work. "The first five subjects had major benefits after 18 months of treatment. A second group is following the same course after six months," said Jonathan Edwards, NiD., professor of rheumatology, the lead investigator. "These patients had endured arthritis for 22 years on average and no longer responded to disease-modifying antirheumatic drugs [DMARDs]."

The researchers theorize that errant B-lymphocytes produce abnormal antibodies that cause RA and perpetuate it. "If so, removing the B-lymphocytes may lead to long-term remission." The treatment combined three drugs known to remove B-lymphocytes in cancer therapy: rituximab (Rituxan, Genentech), prednisolone, and cyclophosphamide (Cytoxan, Bristol-Myers Squibb). "We kept the doses low, and there were no significant side effects," Edwards noted. All patients had 70% improvement after 18 months, although two needed more than one course of treatment.

The researchers also theorize that once the B-lymphocytes are removed, normal cells making normal antibodies would return after a few months, thus "rebooting the immune system." A large controlled study is under way; the data reported at the ACR meeting will be published in Rheumatology (Oxford University Press).

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