Managing refractory Crohn's disease: challenges and solutions

Abstract

The goals of treatment for active Crohn's disease (CD) are to achieve clinical remission and improve quality of life. Conventional therapeutics for moderate-to-severe CD include 5-aminosalicylic acid, corticosteroids, purine analogs, azathioprine, and 6-mercaptopurine. Patients who fail to respond to conventional therapy are treated with tumor necrosis factor (TNF)-α inhibitors such as infliximab and adalimumab, but their efficacy is limited due to primary nonresponse or loss of response. It is suggested that this requires switch to another TNF-α inhibitor, a combination therapy with TNF-α blockade plus azathioprine, or granulocyte and monocyte adsorptive apheresis, and that other therapeutic options having different mechanisms of action, such as blockade of inflammatory cytokines or adhesion molecules, are needed. Natalizumab and vedolizumab are neutralizing antibodies directed against integrin α4 and α4β7, respectively. Ustekinumab is a neutralizing antibody directed against the receptors for interleukin-12 and interleukin-23. Here, we provide an overview of therapeutic treatments that are effective and currently available for CD patients, as well as some that likely will be available in the near future. We also discuss the advantages of managing patients with refractory CD using a combination of TNF-α inhibitors plus azathioprine or intensive monocyte adsorptive apheresis.

Keywords: adalimumab; combination therapy; complete remission; granulocyte and monocyte adsorptive apheresis.

Figure 1

Endoscopic findings at baseline (A) and at week 10 (B). Notes: (A) Black arrowheads indicate the active ulcer. (B) White arrowheads indicate the ulcer scar. Copyright © 2012. The Japanese Society of Internal Medicine. Figure adapted from Ozeki K, Tanida S, Mizushima T, et al. Combination therapy with adalimumab plus intensive granulocyte and monocyte adsorptive apheresis induced clinical remission in a Crohn’s disease patient with the loss of response to scheduled adalimumab maintenance therapy: a case report. Internal Medicine. 2012;51(6):595–599.

Figure 2

The overall changes in the CDAI scores (A) and CRP levels (B) from baseline to 10 weeks after five ADA injections for all five cases in this study. Note: (A) *P=0.024 vs baseline; N=5. (B) **P=0.038 vs baseline; N=5. The comparisons were made by using the Student’s t-test. Copyright © 2012 by S. Karger AG, Basel. Adapted from Ozeki K, Tanida S, Mizoshita T, et al. Combination therapy with intensive granulocyte and monocyte adsorptive apheresis plus adalimumab: therapeutic outcomes in 5 cases with refractory Crohn’s disease. Case Rep Gastroenterol. 2012;6(3):765–771. Abbreviations: ADA, adalimumab; CRP, C-reactive protein; CDAI, Crohn’s disease activity index.