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Top-Down Versus Step-Up Approach for Steroid-Dependent Ulcerative Colitis


From the perspective of a harried primary care physician, it’s very difficult to sort out arguments and data when two respected specialists diametrically disagree.

From the perspective of a harried primary care physician, it’s very difficult to sort out arguments and data when two respected specialists diametrically disagree.

Favoring the Step-Up Strategy
Asher Kornbluth, MD, at Mount Sinai School of Medicine, in New York, favors the current US standard of care, which recommends that patients with severe ulcerative coliltis who end up requiring corticosteroids to stay in control be offered drugs in a traditional "step up" manner-starting with less potent agents thought to have a better safety profile, and adding a "big gun"-an anti–tumor necrosis factor (anti-TNF) agent-only if less toxic agents fail to achieve remission. The crux of his argument is that the "great majority" of patients do not present with severe or fulminant disease and that less potent drugs "achieve clinical improvement" in about 70% of these patients. Dr Kornbluth also notes the toxicity of anti-TNF drugs, which includes delayed hypersensitivity, catastrophic infections, heart failure, hepatotoxicity, and lymphoma. He also presented data suggesting that the value of anti-TNF drugs has been overstated-only 21% of patients treated with them maintain steroid-free remission a the end of 1 year. For all these assertions, Dr Kornbluth presents compelling clinical study data. He notes that the standard-of-care "step-up" strategy has never been compared directly with "top-down" in a clinical study, and given the safety and efficacy concerns, the standard of care should not be altered.

Favoring the Top-Down Strategy
Gary Lichtenstein, MD, at the University of Pennsylvania in Philadelphia took the opposite view, titling his presentation "Top Down Rocks for Ulcerative Colitis." He advocates starting the anti-TNF agent infliximab for patients with ulcerative colitis who need corticosteroids to stay in control. This all seems slightly amusing, unless you’re a patient with ulcerative colitis, or a primary care physician trying to help patients make choices when they read conflicting reports on the Web or elsewhere. Dr Lichtenstein presented what appeared to be equally compelling data showing the risks of waiting to administer more potent agents when the patient reaches the "tipping point"-the need for steroids to stay in control. He cites a lower likelihood of requiring surgery, demonstrated mucosal healing, and a raft of data on the complications from the supposedly less toxic drugs.

Implications for Real-World Practice
As a non-expert physician, I’m at a loss-without going back to the primary papers, it’s fairly difficult to refute either presenter’s argument. Clear science rarely exists in the murky reality of clinical choices that patients and their physicians are stuck with. The debaters appear to agree that no study directly compares the two approaches, so I’d be hesitant to reject the existing standard of care favored by national authorities (Step Up).

Disclosure information (required by the ACG to promote objectivity, balance, and scientific rigor): Dr Kornbluth (Step-Up) indicated no relationships that could be perceived as a conflict of interest. In contrast, Dr Lichtenstein (Top-Down) disclosed that he has relationships with all 3 pharmaceutical companies that produce the "big guns"-the anti-TNF drugs mentioned in his presentation. He is a consultant, and has received research grant or research support from Abbott (adalimumab), Centocor (infliximab), and UCB (certolizumab). I mention this not to dismiss his interpretation of the data, because most pharmaceutical relationships arise after a drug company surveys the literature and finds researchers whose work supports their positions, not the other way around. But most authorities suggest that anyone interpreting clinical recommendations from authorities with business relationships with drug companies or device manufacturers understand the potential for conflict of interest. 

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