After a surgical evaluation, a plan of action should be formulated in a multidisciplinary fashion to determine how medical management will proceed. For those with an established diagnosis of ulcerative colitis, medical therapy can often be stopped postoperatively and the patient can be monitored prospectively for pouch complications including possible new-onset Crohn’s disease. For those who undergo surgery for the management of Crohn’s disease, though a resection completed with negative margins does induce remission, nearly 90% can be expected to have histologic, endoscopic, or clinical recurrence by 1 year. A randomized controlled trial showed that postoperative anti-TNF therapy can reduce this risk to 9% [35]. Unfortunately, a subsequently conducted large, multicenter, randomized controlled trial comparing postoperative infliximab to placebo was terminated early because of a lack of a statistically significant difference in clinical recurrence between the 2 groups at week 74. However, this lack of demonstrated efficacy may have been obscured by the relatively mild phenotype of the enrolled participants, who had a median CDAI score of 105.5 at baseline [36]. Based on available data, the AGA does conditionally recommend postoperative anti-TNF and/or thiopurine therapy for those patients with Crohn’s disease who are in a surgically induced remission [37]. The patients who are most likely to benefit from postoperative medical therapy are those who have the highest risk of recurrence, namely those who were young at the time of diagnosis, had a short disease duration prior to surgery, have multiple sites of disease, and who use tobacco products [34].
Emerging and Future Options
Despite the improved clinical outcomes seen since the introduction of TNF antagonists for the management of IBD, there remains a significant need for additional medical therapies. Fortunately, the armamentarium is expected to expand dramatically over the next decade.
Based on our improved, and evolving understanding of the pathogenesis of IBD, several new biochemical targets have emerged, offering novel ways to modulate the cytokine cascade which drives IBD [38]. Well over a dozen phase II and phase III trials for IBD therapeutic agents are ongoing, including biologic agents targeting interleukin-23, β7-Integrin, and MAdCAM-1, as well as small molecule agents targeting the JAK/STAT pathway and the sphingosine-1-phosphate receptor modulators [39]. As new agents are approved, it may be possible to develop a more patient-centered approach to care by targeting therapies to the particular pathogenesis of each patient’s disease. Nevertheless, integrating these therapies into practice algorithms will remain a challenge in the absence of meaningful comparative effectiveness trials [40].
Conclusion
When evaluating a patient who seems to have failed anti-TNF therapy for IBD, the first step is to confirm that active inflammatory disease is present. This process includes ruling out other potential causes of the patient’s symptoms, including infectious colitis, and ideally includes obtaining objective evidence of inflammation, whether through non-invasive biomarkers, an endoscopic evaluation and/or cross-sectional imaging. Once active IBD is confirmed, reactive therapeutic drug monitoring can help elucidate the likely mechanism of drug failure, which in turn can guide medical decision making.
Corresponding author: Anita Afzali MD, MPH, The Ohio State University Wexner Medical Center, 395 West 12th Ave, Room 280, Columbus, OH 43210, Anita.Afzali@osumc.edu.
Financial disclosures: Dr. Afzali has served as a speaker/consultant for Abbvie, UCB, Takeda, Pfizer, Janssen; on the advisory board of Abbvie, UCB; received grant support from UCB; and is a board member of IBD Horizons.