NEW YORK, NY—The year just past included some remarkable advances in rheumatology research and treatment but also left some major clinical problems unsolved. A "virtual roundtable" of CIAOMed Editorial Board members discussed both the advances and the problems pending. Participants were 

● Graciela S. Alarcón, MD, MPH (Jean Knight Lowe Professor of Medicine in Rheumatology, University of Alabama, in Birmingham)
● Robin K. Dore, MD (Clinical Professor of Medicine, University of California, in Los Angeles)
● Paul Emery, MA, MD, FRCP (Professor of Rheumatology, University of Leeds, in the UK)
● Roy M. Fleischmann, MD (Clinical Professor of Medicine, University of Texas Southwestern Medical Center, in Dallas)
● Josef S. Smolen, MD (Professor of Internal Medicine, University of Vienna, and Chairman, Center for Rheumatic Diseases, Lainz Hospital, in Austria)
● Désirée van der Heijde, MD (Professor of Rheumatology, University Hospital, in Maastricht, The Netherlands)

Big Deals: What Changed Rheumatology Most in 2006

The CIAOMed Editorial Board pointed to new data on the possibility of durable remission in rheumatoid arthritis (RA), new drugs, and new approaches to drug therapy as the most important developments from the clinical standpoint.

Dr. Fleischmann said, "The results of group 4 of the BeST study demonstrate that treating to remission is important and that, at least in early disease, aggressive therapy may induce a remission which persists for at least a period of time even if anti-TNF therapy is discontinued." He noted the need for evidence that these results are reproducible. Dr. Smolen added that the increased use of activity indices, aiming to achieve low disease activity or remission in RA, marks a significant change.

Dr. Alarcón pointed to major advances in RA therapeutics, including the availability of abatacept (OrenciaR, Bristol-Myers Squibb) and the increased number of products now advancing in the clinical trials pipeline. Dr. Emery said that the emergence of "target-led therapy" has changed the face of rheumatology, and Dr. Dore said that an example of that is the availability of rituximab (RituxanR, Genentech), which provides an additional option for RA patients and an alternative in cases of TNF-inhibitor failure.

Dr. Alarcón added, "The concept of a ‘window of opportunity' for the treatment of RA continues to be reinforced with data. The dissociation between inflammation and destruction in the rheumatoid joint is also gaining acceptance—and its basis is being elucidated."

And there were some surprises...

Drs. Smolen and Emery both cited the efficacy of JAK3 inhibitors in RA as the big surprise of 2006. Dr. Smolen was also surprised by the poor showing of biomarkers (except for C-related peptide, CRP) as predictors of disease activity.

"I maintain a healthy degree of skepticism, so I cannot say that I was truly surprised by what I read and what I saw. I was, however, a bit taken aback by the misinterpretation of the data regarding bisphosphonates and osteonecrosis of the mandible by patients and oral surgeons alike," Dr. Alarcón said.

Unsolved Problems: What We Need Now

Lupus looms as a serious unsolved problem in rheumatology, according to Drs. Dore and Alarcon. "Advances in the treatment of lupus and other rheumatic diseases lag behind the advances made in RA. Progress is being made, but results of ongoing studies will not be available any time soon. Limiting factors for lupus trials include the number of patients and of researchers needed for these trials to be successful," Dr. Alarcon said.

Drs. Fleischmann and Emery both said that the TNF failures remain a major unsolved problem. "Will abatacept be effective in the long term, and will the safety profile of rituximab allow it to be used efficiently (safely and effectively) for many years?" Dr. Fleischmann asked.

Dr. van der Heijde raised a related issue. "There was no inhibition of structural damage in ankylosing spondylitis (AS) by the TNF-blocker etanercept (EnbrelR, Amgen-Wyeth), in concordance with the dissociation between disease activity and structural damage in AS."

Dr. Smolen added, "Why does always only a fraction of patients respond to given therapies, including treatments that target the same molecule, such as TNF-α?" He also wondered why there is often no added efficacy but increased toxicity when different targeted therapies are combined.

On the horizon for 2007

For 2007, Dr. Smolen is expecting to see better responses in RA by targeting populations of patients more specifically, better biomarker data, the resolution of the riddle of anti-CCP, and better therapies for lupus. Dr. Alarcón awaits results of the ongoing trials of rituximab and mycophenotale in lupus but said, "They will not see the light this year."

Dr. Dore is anxious to see more data on denosumab (Amgen), and Dr. Fleischmann looks forward to phase II/III data that will show that JAK3 inhibition is safe and effective.

Beyond the Clinic: Economic, Political, and Social Potholes on the Road Ahead

Rheumatology practice is affected by the world outside the clinic and lab, and most of the Editorial Board foresaw new challenges in those areas.

Dr. Alarcón said that, for US physicians, demographic shifts are likely to affect the practice of rheumatology. "The frequency distribution of diseases more common to Hispanics may also alter the practice of rheumatology as they migrate into areas of the country where they had not lived before. For example, rheumatologists need to be aware of the increased frequency of lupus among Hispanics and to consider this diagnosis in any young Hispanic woman presenting with arthritis," she said.

Dr. Dore predicted that "pay for performance" will be an ongoing problem for rheumatologists, as will the "doughnut hole" in Medicare D drug coverage. Dr. Fleischmann expects a continuing decline in reimbursement rates for rheumatologists and increased pressure "to demonstrate effectiveness of therapy from the payer's standpoint."

Insurers reducing reimbursement rates for biologics to reduce costs may also be a problem. "Not just the incremental income from the copayment, but any additional cost may cause the patient to drop the medication completely. That is, the insurer may save the most if it raises the copay to the level at which the patient drops the medication completely. More stringent requirements for injectible medications also make access more difficult and therefore reduce costs to the insurer," Dr. Dore said.

Dr. Alarcón seconded this point, criticizing "the limitations on the use of biologic therapies imposed by third party payers and with it the tremendous inequalities in the delivery of optimal care to our patients (in the richest country in the world)." Dr. Emery said that the high cost of biologics are also a problem for rheumatologists in the UK.

Dr. Dore warned that in the US, the push for universal health insurance coverage may adversely affect reimbursement. "There may be an assumption that more insureds are better for physicians economically, and therefore physicians should pay for this additional coverage by a tax or reduced reimbursement," Dr. Dore said.

This point was promptly illustrated by California governor Arnold Schwarzenegger, who has proposed just such an insurance program for his state, to be paid for in part by a 2% levy on physicians.

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