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.

Distinct transcriptional signatures in purified circulating immune cells drive heterogeneity in disease location in IBD

“…The above combination of evidence suggests that the modulation of the FOXO pathway could be part of a molecular phenotype associated with the pathogenesis at the primary disease site(s), although further independent validation in larger cohorts is warranted. Although it is not clear if and how the ileal phenotype affects the potential relationship between IBD disease burden and the FOXO3 mutation, the refractory nature of ileal CD58 as manifested across multiple clinical trials and additional meta-analysis59 60 suggests that novel targets are indeed required. FOXO pathway members ( BCL6, CDKN1A, BTG1, GADD45A, KLF4 ) which are upregulated in ileal CD patients, could potentially fill this therapeutic gap (table 2).…”

Interleukin-34 as a marker for subclinical proliferative lupus nephritis

“…8–10 IL-34 was found to be involved in the inflammation process seen in diseases such as rheumatoid arthritis, 11 Sjögren’s syndrome 12 and inflammatory bowel disease. 13 IL-34 can stimulate the production of IL-6, IFN γ-inducible protein (IP) 10 and monocyte chemoattractant protein-1 (MCP-1). 10 IL-6, 14 IP10 15 and MCP-1 16 are among the players that contribute to the pathogenesis of SLE.…”

Thalidomide-induced sinus bradycardia in Crohn’s disease: case report and literature review

“…4,5 However, refractory disease, including non-response or intolerance to thiopurines, and loss of response to biologics remain a clinical challenge. 6,7 With potential effects of immunomodulation and suppression of tumor necrosis factor-a (TNF-a), thalidomide has been shown to be effective in treating refractory CD in retrospective studies and in a landmark randomized, controlled trial. [8][9][10][11][12][13][14] Recently, the role of thalidomide in inducing and maintaining mucosal healing in patients with CD has been reported in case series and a prospective open-label study that was performed at our center.…”