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Managing refractory Crohn's disease: challenges and solutions.

Tanida S, Ozeki K, Mizoshita T, Tsukamoto H, Katano T, Kataoka H, Kamiya T, Joh T - Clin Exp Gastroenterol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Aichi Prefecture, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

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):595–599.9
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f1-ceg-8-131: 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):595–599.9

Mentions: GMA depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines and has been used to treat patients with CD. In the clinical setting, as a nondrug intervention, weekly GMA when added to scheduled IFX maintenance therapy was effective in a CD patient with active disease while under IFX therapy.77 This was followed by a similar report indicating that the addition of intermittent weekly GMA to scheduled IFX maintenance was effective in a CD case also refractory to IFX alone.78 Moreover, a report investigated the efficacy of intensive GMA (two sessions per week) in combination with ADA as remission induction therapy in five consecutive cases with refractoriness to medications, including anti-TNF-α therapies such as IFX and ADA. At week 10 post-ADA treatments, clinical remission together with normal C-reactive protein levels were achieved in all five cases, while endoscopic findings, based on the simple endoscopic score for CD, reflected marked improvement in three cases and partial improvement in two cases that had extensive deep longitudinal CD lesions (Figure 1 and Table 1). The CDAI and C-reactive protein values at baseline were 324±118 and 4.9±3.3 mg/dL, respectively; the corresponding values after treatment were 100±28 (P=0.024) and 0.2±0.2 mg/dL (P=0.038, Figure 2). All five cases responded well to combination therapy of intensive GMA plus ADA, achieving clinical remission, normal serum C-reactive protein levels, and marked healing of their CD lesions. No adverse events were observed in that study.7


Managing refractory Crohn's disease: challenges and solutions.

Tanida S, Ozeki K, Mizoshita T, Tsukamoto H, Katano T, Kataoka H, Kamiya T, Joh T - Clin Exp Gastroenterol (2015)

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):595–599.9
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401331&req=5

f1-ceg-8-131: 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):595–599.9
Mentions: GMA depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines and has been used to treat patients with CD. In the clinical setting, as a nondrug intervention, weekly GMA when added to scheduled IFX maintenance therapy was effective in a CD patient with active disease while under IFX therapy.77 This was followed by a similar report indicating that the addition of intermittent weekly GMA to scheduled IFX maintenance was effective in a CD case also refractory to IFX alone.78 Moreover, a report investigated the efficacy of intensive GMA (two sessions per week) in combination with ADA as remission induction therapy in five consecutive cases with refractoriness to medications, including anti-TNF-α therapies such as IFX and ADA. At week 10 post-ADA treatments, clinical remission together with normal C-reactive protein levels were achieved in all five cases, while endoscopic findings, based on the simple endoscopic score for CD, reflected marked improvement in three cases and partial improvement in two cases that had extensive deep longitudinal CD lesions (Figure 1 and Table 1). The CDAI and C-reactive protein values at baseline were 324±118 and 4.9±3.3 mg/dL, respectively; the corresponding values after treatment were 100±28 (P=0.024) and 0.2±0.2 mg/dL (P=0.038, Figure 2). All five cases responded well to combination therapy of intensive GMA plus ADA, achieving clinical remission, normal serum C-reactive protein levels, and marked healing of their CD lesions. No adverse events were observed in that study.7

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Aichi Prefecture, Japan.

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.

No MeSH data available.


Related in: MedlinePlus