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300952

AZATHIOPRINE AND BIOLOGICAL TREATMENT GENETIC ASSOCIATION WITH CLINICAL RESPONSE AND TOXICITY IN INFLAMMATORY BOWEL DISEASE PATIENTS

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Last updated: 25 Dec 2024

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Abstract

Inflammatory Bowel Disease (IBD) involves a variety of conditions, particularly Crohn's disease (CD) and ulcerative colitis (UC). IBD is characterized by a chronic inflammatory process of the patient's gut. This review aims to summarize the pharmacogenetics of biologics approved for IBD and the correlation with azathioprine-metabolizing enzymes and adverse reactions, therefore highlighting a likely relationship between particular polymorphisms and therapeutic response. Therefore, we reviewed and discussed the activities of therapeutic drug monitoring (TDM) protocols that use monoclonal antibodies (mABs) with a particular attention to the integration of other actions aimed to exploit the most effective and safest medications for IBD cases. The pharmacotherapy of IBD (CD and UC) has experienced a great advancement with the advent of mABs which have peculiar pharmacokinetic properties differentiating them from chemical agents, like aminosalicylates, antimetabolites (e.g., azathioprine (AZA), 6-mercaptopurine (6MP)), and methotrexate), and immunosuppressant agents (steroids and cyclosporine). But clinical studies showed that biologicals might have pharmacokinetic variability which can affect the anticipated clinical outcomes, beyond primary resistance phenomena. Thus, TDM protocols are applied to the doses of medications according to the required serum mABs levels. This aims to maximize the favourable effects of mABs and minimize the toxicity. But, the presence of particular genetic polymorphisms in patients might determine a different outcome in response to treatment, indicating the heterogeneity of the effectiveness among IBD cases. Indeed, many reports demonstrated significant associations between polymorphisms and response to biologics. In conclusion, the improvement of TNF-, TNFR and IL-1 pharmacogenetics could be the best approach toward a targeted treatment for IBD.Pre-therapy genotyping has to be integrated with IBD therapeutic guidelines, as it is the most suitable approach to choose the most appropriate biologicals for each case. Also, the addition of pharmacodynamic markers (including serum, cellular, or tissue concentrations of TNF-alpha and IL-8) might boost the predictive performance of models and, eventually, control the disease with a significant improvement in quality of life (QOL).

DOI

10.21608/bfsa.2023.300952

Keywords

Pharmacogenetic, genetic polymorphism, inflammatory bowel diseases, Crohn's Disease, ulcerative colitis, SNPs, genotype, Azathioprine, Thiopurine, Biological therap

Authors

First Name

Nashwa

Last Name

Eltantawy

MiddleName

-

Affiliation

Department of Clinical Pharmacy, Faculty of Pharmacy, Horus University,New Damietta Egypt

Email

nashwaeltantawy@gmail.com

City

-

Orcid

-

First Name

Amira

Last Name

Kassem

MiddleName

B.

Affiliation

Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Damanhur University, Egypt

Email

amira.kassem@pharm.dmu.edu.eg

City

-

Orcid

0000-0003-4195-6036

First Name

Islam

Last Name

Elzayyadi

MiddleName

Abd El-Hamid

Affiliation

Depatment of Hepatology & Gastroenterology, Faculty of Medicine, Mansoura University, Egypt

Email

-

City

-

Orcid

-

First Name

Ahmed

Last Name

Elberry

MiddleName

A.

Affiliation

Department of pharmacology, Faculty of Medicine, Beni-Suef University, Egypt

Email

berry_ahmed@yahoo.com

City

-

Orcid

-

First Name

Layla

Last Name

Salah

MiddleName

M.

Affiliation

Department of Clinical pathology, Faculty of Medicine, Mansoura University, Egypt

Email

layla_sarwat@hotmail.com

City

-

Orcid

-

First Name

Mohamed

Last Name

Abdelrahim

MiddleName

EA

Affiliation

Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Egypt

Email

mohamedemam9@yahoo.com

City

-

Orcid

0000-0003-0227-8404

Volume

46

Article Issue

1

Related Issue

41495

Issue Date

2023-06-01

Receive Date

2022-11-17

Publish Date

2023-06-01

Page Start

305

Page End

330

Print ISSN

1110-0052

Online ISSN

3009-7703

Article File

BFSA_Volume 46_Issue 1_Pages 305-330.pdf

PDF . 1.3MB

Link

https://bpsa.journals.ekb.eg/article_300952.html

Detail API

https://bpsa.journals.ekb.eg/service?article_code=300952

Order

300,952

Type

Original Article

Type Code

1,096

Publication Type

Journal

Publication Title

Bulletin of Pharmaceutical Sciences Assiut University

Publication Link

https://bpsa.journals.ekb.eg/

MainTitle

AZATHIOPRINE AND BIOLOGICAL TREATMENT GENETIC ASSOCIATION WITH CLINICAL RESPONSE AND TOXICITY IN INFLAMMATORY BOWEL DISEASE PATIENTS

Details

Type

Article

Created At

25 Dec 2024