AMSTERDAM, The Netherlands – Pre-symptomatic diagnosis of rheumatoid arthritis (RA), followed by treatment with one of a range of new and developing therapies, brings the promise of a ‘cure' for the disease within 10 years. For the moment, however, the traditional X-ray remained the best method of diagnosing RA, and ‘cheap' methotrexate (Mtx) remains the standard first-line therapy. That was the cautious verdict of Josef Smolen, MD, Professor of Medicine and Chairman of the Center for Rheumatic Diseases at the University of Vienna, Austria, delivering a state of the art address on RA to the EULAR meeting.¹

Doctors, he said, should continue to prescribe methotrexate as first-line treatment for RA patients. "A significant number of people respond well to methotrexate, which is cheap and performs as well as any of the biological agents for some patients. I certainly have many patients who have achieved remission on this cheapie drug. There are several new therapeutic approaches in the pipeline giving hope that we will achieve 100% remission within 10 years. Alas, nothing so far studied produces better results than what we already have: methotrexate with regular monitoring and the opportunity to prescribe anti-TNF drugs for nonresponders," Dr. Smolen said. Dr. Smolen commented that he also remains to be convinced of the value of MRI scanning instead of X-ray in RA. "It's not yet clear whether erosions picked up by MRI are truly an early sign of the disease and associated with future functional disability." But 10 years after the emergence of anti-TNF blockers,

Dr. Smolen said that patients were still suffering: with up to 60% of patients in the clinic not reaching American College of Rheumatism (ARC) 50 response and up to 75% not reaching ARC 70 response. Remission of RA was now the "true aim" of rheumatology – with pre-symptomatic diagnosis of the disease along with aggressive treatment of early disease looking to be the most promising avenues of study.

"We already know that early therapy is especially effective and that after five years, patients given disease-modifying anti-rheumatic drug (DMARD) treatment at three months from onset of symptoms have not even reached the baseline of those who started treatment even nine months later – and these patients have a higher responsiveness to functional disability than those who begin treatment later on," he explained.

"Research is now suggesting that RA antibodies precede the evolution of symptoms and that inflammatory infiltrate can be present in the osteocytes in clinically unaffected joints. At eight to 12 weeks after onset of symptoms, 12% of patients already have erosion suggesting these events have started before clinical symptoms appear and that pre-arthritis autoimmunity leads to symptomatic synovitis and eventually the pain and swelling of RA," he said.

This new understanding of the onset of RA will underpin new approaches to treatment as well as prevention, Drl Smolen explained. "Now that we suspect that patients may have auto-antibodies several years before the onset of RA, we are now considering targeting these auto-antibodies in order to identify those people who should be treated at an early stage," he explained, announcing the imminent launch of an investigation of epidemiological data to address the significance of high titer rheumatoid factor (RF), anti-CRP levels, and other markers of RA, in healthy people.

But despite an exciting existing and forthcoming research program, Dr. Smolen's message to rheumatology delegates was to urge caution. "We know there is a multiplicity of inflammatory cytokines and we may need to attack more than one at a time in order to get results and prevent bone destruction and consequent irreversible functional disability. But it is not just the heterogeneity of RA that may explain why we are failing to achieve effective therapy for all. The degree of clinical activity may also impair response to therapy. We need to be sure that combinations of therapies are effective without causing toxicity."

He adamantly refused to be pushed into a more adventurous stance. During questions, he came under fire from UK rheumatologist, Paul Emery, MD, who contended that Dr. Smolen was mistaken on the lack of evidence for the use of MRI in RA diagnosis. Dr. Emery warned that patients could deteriorate while clinicians waited for more evidence of MRI reliability. But Dr Smolen remained unmoved. Promising to continue the debate with Dr. Emery in private, he told the meeting: "I still need to be convinced."

Reference

1. Smolen, J. Treatment of RA – now and into the future. Presented at: EULAR Meeting 2006; 21-24 June 2006; Amsterdam, The Netherlands.