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Inflammatory Bowel Disease Treatment Trends Highlighted at Conference

Inflammatory Bowel Disease Treatment Trends Highlighted at Conference

New insights into how clinicians might approach treatment for patients with inflammatory bowel disease (IBD) highlighted the Crohn’s & Colitis Foundation’s Clinical & Research Conference, held recently in Hollywood, Florida.

Reporting on the conference for www.consultantlive.com, Jeffrey Hertzberg, MD, MS, offered the following observations:

• A recurring theme emerged suggesting that a purely dichotomous understanding of whether to start treatment for patients who have IBD with anti–tumor necrosis factor (anti-TNF) agents is becoming an outdated view.

• In a conference that tended to focus on the use of the newest, most expensive biologic agents, a speaker noted that the 5-ASA agents remain the mainstay of therapy for most patients with ulcerative colitis.

• Making science-based decisions about what to do when patients with IBD experience adverse events with the use of immunomodulators and biologics was characterized as a difficult undertaking that even the most experienced and skilled gastroenterologists find challenging.

• All patients with IBD should receive aggressive ongoing assessment of their inflammatory state and its response to immunomodulators, anti-TNF drugs, and other agents, according to multiple speakers.

• New drugs are needed for patients with IBD because many “reach the end of the line” with existing therapies, cited studies showed.

Debate continues about whether to try other agents for IBD before starting treatment with anti-TNF agents, Dr Hertzberg noted, but the discussion has been based on the presumption that anti-TNF drugs carry a high risk of serious infections and malignancies. Many conference presenters cited accumulating evidence suggesting that this risk has been overstated.

The trend seems to be toward a modified “step-up” approach to therapy, beginning with less aggressive agents in the setting of mild disease but rapidly progressing to anti-TNF agents. The old paradigm—treating on the basis of symptoms—is being supplanted by a new paradigm of rapidly stepping up or changing therapy on the basis of objective markers of inflammation.

In a presentation on the 5-ASA agents (sulfasalazine, mesalamine, and balsalazide), Sunanda V. Kane, MD, MSPH, Mayo Clinic College of Medicine, Rochester, Minnesota, noted that cost and concerns about life-threatening adverse effects limit more widespread use of the anti-TNF agents, and in general, have prevented their use as first-line agents. There is no evidence to support any claim of superiority of one 5-ASA agent over any other, Dr Kane suggested, but there may be some value in combining two 5-ASA agents to maximize absorption.

Given therapeutic equivalency, insurance considerations often determine the preferred 5-ASA for a given patient, and e-Prescribing systems may simplify the process by preemptively alerting physicians to insurance-approved formulary. The 5-ASA agents may be limited by patient noncompliance because of adverse effects.

In his presentation on managing adverse events, Miguel Regueiro, MD, University of Pittsburgh, made the point that clinical practice is based not on science but rather on intuition and educated guesswork. Therapy with the immunomodulating thiopurines (6-MP and azathioprine) or the anti-TNF agents is stopped for adverse events—ranging from self-limited skin complications to life-threatening opportunistic infections, lymphomas, and other malignancies—in 10% to 11% of cases, he noted.

Thiopurines do not appear to have significantly safer profiles than the anti-TNF agents—both may be associated with rare but serious adverse events, Dr Regueiro suggested. Thiopurines may be more closely linked to viral infections and lymphoma and certain other malignancies and the anti-TNFs to bacterial infections, fungal infections, and immune-mediated psoriaform skin reactions. For both drug classes, the serious events are uncommon enough to justify their use in patients not responding well to first-line agents.

The evolving treatment monitoring strategy for patients with IBD, based on the presentations of multiple speakers, includes periodic assessment of patient symptoms with systematic scoring systems and periodic assessment of objective endoscopic findings with systematic scoring systems that quantify the degree of objective inflammation. Also involved are trough drug level monitoring for patients who are receiving anti-TNF therapy, C-reactive protein level measurement, fecal calprotectin level, checking for the development of antibodies to the drug for nonresponders to anti-TNF therapy, cross-sectional imaging, and maintaining a high degree of suspicion for infection if treatment appears to be “failing.”

Jean-Frederic Colombel, MD, Mount Sinai School of Medicine in New York City, described anti-TNF agents in the pipeline that clinicians may be using in the near future: golimumab, ustekinemab, vedolizumab, and tofacitinib. Promising but future-oriented treatments that eventually may come to large clinical trials include mesenchymal stem cell transfer and autologous hematopoietic stem cell transplantation, he noted.

Given the deepening understanding of the genetic commonality of ulcerative colitis and Crohn disease, clinicians probably will not obsess quite so much about distinguishing between the disorders in the future, suggested Dr Maria Abreu of the University of Miami. Treatment modalities have started converging, and this trend probably will accelerate.

 
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