25 Years in Arthritis: New Treatments, New Hope

Hadler said these disease-modifying anti-rheumatic drugs (DMARDs), as they are now called, "came and went with fleeting zeal because none of [them] were dramatically or consistently effective."

That changed with methotrexate, which was found to induce remissions or at least stabilize disease in most patients with good tolerability at weekly doses of 10 to 20 mg.

Of course, it too has side effects -- its label includes a dozen "black box" warnings, although these are mainly concerns at the higher doses used in cancer therapy -- and about a third of patients still show disease progression, Hadler said.

In With the Biologics

The breakthrough for those patients came in 1998, when two biologic drugs targeting the cytokine known as tumor necrosis factor (TNF) were launched in the United States.

These were infliximab (Remicade), a monoclonal antibody against TNF, and etanercept (Enbrel), a soluble version of a TNF receptor protein, both of which sop up and inactivate TNF in circulation.

They emerged from basic science research beginning in the mid-1980s that identified TNF as a major player -- perhaps the major player -- in chronic inflammatory diseases.

Twenty-five years ago, RA was well understood to be an autoimmune disease. A 1984 report of a National Institutes of Health-sponsored conference on the condition, published in Annals of Internal Medicine, described in great detail the role of T lymphocytes.

It also reviewed findings on abnormal behavior of B cells, which have since become another target for biologic drugs in arthritis.

But the 15-page report contained not a single mention of TNF and only few references to cytokines of any kind.

In fact, it wasn't until the following year that TNF -- which, as its name implied, was first noticed for its tumor-killing ability -- was found to promote inflammatory activity or otherwise regulate immune function.

Thus, the trip from bench to bedside for these powerful new RA treatments took just 13 years.

In line with recommendations from the American College of Rheumatology, physicians surveyed by MedPage Today and ABC News unanimously agreed that anti-TNF biologics were the treatment of choice for patients with persistent disease despite methotrexate therapy.

"The TNF blockers ... have revolutionized rheumatology practice, since their effectiveness is better than any of our prior drugs, with better safety," wrote Dr. Theodore Fields of Weill Cornell Medical College in New York City, in an e-mail.

As part of the poll, respondents were asked what they would have told certain hypothetical patients to expect in 1984, and how that had changed in 2009.

In 1984, for a newly diagnosed patient, a woman in her early 40s, "I'd tell her we could offer her aspirin at high doses (dosed based on GI side effects or until their ears ring), oral gold, gold shots each week, but they all have major side effects, and we have no idea how they work," said Dr. P.J. Utz of Stanford University in Palo Alto, Calif, in an e-mail.

"What I wouldn't tell her is that steroids are really bad, she could end up in a wheelchair from her RA, and as her joints wear out we are getting better and better at joint replacements, but they are imperfect," Utz added.

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