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Adalimumab for the treatment of Crohn's disease.

Cassinotti A, Ardizzone S, Porro GB - Biologics (2008)

Bottom Line: Adalimumab (ADA) is a subcutaneously administered, recombinant, fully human, IgG1 monoclonal antibody that binds with high affinity and specificity to human TNF-alpha, thus modulating its biologic functions and its proinflammatory effects.To review the available data on ADA in CD for biological properties, efficacy, and safety.ADA appears to be effective in inducing and maintain clinical remission in CD, including patients not manageable with IFX.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences, Chair of Gastroenterology, "Luigi Sacco" University Hospital, Milan, Italy.

ABSTRACT

Introduction: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by a relapsing-remitting course with trans-mural inflammation of potentially any section of the digestive tract. Adalimumab (ADA) is a subcutaneously administered, recombinant, fully human, IgG1 monoclonal antibody that binds with high affinity and specificity to human TNF-alpha, thus modulating its biologic functions and its proinflammatory effects.

Aims: To review the available data on ADA in CD for biological properties, efficacy, and safety.

Methods: Electronic searches were conducted using the Pubmed and SCOPUS databases from the earliest records to April 2008. The search terms used were "adalimumab", "anti-TNF", "TNF-alpha", "biologicals", "inflammatory bowel disease", and "Crohn's disease". Reference lists of all relevant articles were searched for further studies.

Results: Available studies suggest that ADA has the potential to induce and maintain clinical response and remission in moderate-severe CD, both in anti-TNF-naïve patients and in subjects who lost their response and/or became intolerant to infliximab (IFX). ADA seems also effective in maintaining corticosteroid-free remission and obtaining complete fistula closure (although no specific randomized trials are available). No concomitant immunosuppressors seem to be necessary. Side effects appear similar to IFX, while site-injection reactions are frequent and specific. Data on immunogenicity and its clinical impact are uncertain.

Conclusions: ADA appears to be effective in inducing and maintain clinical remission in CD, including patients not manageable with IFX. Successive clinical practice and further on going trials will confirm a positive role for ADA as a new anti-TNF treatment in CD. The impact on clinical management or on resources should be more studied.

No MeSH data available.


Related in: MedlinePlus

Efficacy of adalimumab (ADA) as induction therapy in CLASSIC I trial for Crohn’s disease. Derived from Hanauer et al (2006).*p = 0.001; **p = 0.002; ^p < 0.05; °p = 0.01; °°p = 0.007.
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f1-btt-2-763: Efficacy of adalimumab (ADA) as induction therapy in CLASSIC I trial for Crohn’s disease. Derived from Hanauer et al (2006).*p = 0.001; **p = 0.002; ^p < 0.05; °p = 0.01; °°p = 0.007.

Mentions: IFX is an intravenously administered chimeric monoclonal antibody of the immunoglobulin (Ig) G1 subclass and comprises 75% human and 25% mouse sequences (Figure 1). The presence of this murine component provides a source of potential immunogenicity for humans. In facts, chimeric antibodies, such as IFX, can induce strong human anti-chimeric antibody (HACA) responses when administered to patients; these are referred to as antibodies to infliximab (ATI) and have been detected in 30% to 61% of patients treated with episodic IFX treatment compared with 7% to 10% of patients on scheduled IFX regimen (Baert et al 2003; Farrell et al 2003; Hanauer et al 2004). In the treatment of chronic disorders such as CD, for which large doses (or repeat dosing) of monoclonal antibodies may be required, the incidence of HACA has been associated with a shortening of the half-life of the drug in serum and a secondary loss of efficacy, in addition to potential infusion reactions, kidney damage and serum sickness.


Adalimumab for the treatment of Crohn's disease.

Cassinotti A, Ardizzone S, Porro GB - Biologics (2008)

Efficacy of adalimumab (ADA) as induction therapy in CLASSIC I trial for Crohn’s disease. Derived from Hanauer et al (2006).*p = 0.001; **p = 0.002; ^p < 0.05; °p = 0.01; °°p = 0.007.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2727899&req=5

f1-btt-2-763: Efficacy of adalimumab (ADA) as induction therapy in CLASSIC I trial for Crohn’s disease. Derived from Hanauer et al (2006).*p = 0.001; **p = 0.002; ^p < 0.05; °p = 0.01; °°p = 0.007.
Mentions: IFX is an intravenously administered chimeric monoclonal antibody of the immunoglobulin (Ig) G1 subclass and comprises 75% human and 25% mouse sequences (Figure 1). The presence of this murine component provides a source of potential immunogenicity for humans. In facts, chimeric antibodies, such as IFX, can induce strong human anti-chimeric antibody (HACA) responses when administered to patients; these are referred to as antibodies to infliximab (ATI) and have been detected in 30% to 61% of patients treated with episodic IFX treatment compared with 7% to 10% of patients on scheduled IFX regimen (Baert et al 2003; Farrell et al 2003; Hanauer et al 2004). In the treatment of chronic disorders such as CD, for which large doses (or repeat dosing) of monoclonal antibodies may be required, the incidence of HACA has been associated with a shortening of the half-life of the drug in serum and a secondary loss of efficacy, in addition to potential infusion reactions, kidney damage and serum sickness.

Bottom Line: Adalimumab (ADA) is a subcutaneously administered, recombinant, fully human, IgG1 monoclonal antibody that binds with high affinity and specificity to human TNF-alpha, thus modulating its biologic functions and its proinflammatory effects.To review the available data on ADA in CD for biological properties, efficacy, and safety.ADA appears to be effective in inducing and maintain clinical remission in CD, including patients not manageable with IFX.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences, Chair of Gastroenterology, "Luigi Sacco" University Hospital, Milan, Italy.

ABSTRACT

Introduction: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by a relapsing-remitting course with trans-mural inflammation of potentially any section of the digestive tract. Adalimumab (ADA) is a subcutaneously administered, recombinant, fully human, IgG1 monoclonal antibody that binds with high affinity and specificity to human TNF-alpha, thus modulating its biologic functions and its proinflammatory effects.

Aims: To review the available data on ADA in CD for biological properties, efficacy, and safety.

Methods: Electronic searches were conducted using the Pubmed and SCOPUS databases from the earliest records to April 2008. The search terms used were "adalimumab", "anti-TNF", "TNF-alpha", "biologicals", "inflammatory bowel disease", and "Crohn's disease". Reference lists of all relevant articles were searched for further studies.

Results: Available studies suggest that ADA has the potential to induce and maintain clinical response and remission in moderate-severe CD, both in anti-TNF-naïve patients and in subjects who lost their response and/or became intolerant to infliximab (IFX). ADA seems also effective in maintaining corticosteroid-free remission and obtaining complete fistula closure (although no specific randomized trials are available). No concomitant immunosuppressors seem to be necessary. Side effects appear similar to IFX, while site-injection reactions are frequent and specific. Data on immunogenicity and its clinical impact are uncertain.

Conclusions: ADA appears to be effective in inducing and maintain clinical remission in CD, including patients not manageable with IFX. Successive clinical practice and further on going trials will confirm a positive role for ADA as a new anti-TNF treatment in CD. The impact on clinical management or on resources should be more studied.

No MeSH data available.


Related in: MedlinePlus