TPMT and HLA-DQA1-HLA-DRB genetic profiling to guide the use of azathioprine in the treatment of interstitial lung disease: First experience

Taha, Nada; Hosein, Karishma; Grant-Orser, Amanda; Lin-Shaw, Ammy; Mura, Marco

doi:10.1016/j.pupt.2020.101988

Cited by 3 publications

(4 citation statements)

References 30 publications

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“…The British Thoracic Society recommended the use of iv rather than oral CYC, 89 given preferable side effect profile. 107 The rate of leukopenia, severe infections, and gonadal toxicity were reduced in the iv administration route, compared with oral, without differences in patient outcomes. 59 The recommended iv dose is 500–750 mg/m 2 monthly, 78 but frequency can be increased in severe cases with hypoxemic respiratory failure.…”

Section: Treatment Approachesmentioning

confidence: 98%

“… 106 A recent study demonstrated that genetic testing was associated with a significantly reduced incidence of major adverse events and a lower rate of AZA discontinuation, but the total number of adverse events did not change, as available genetic testing does not predict the risk of liver dysfunction or other side effects. 107 While the cost-effectiveness of systematic genetic testing for AZA has not yet been demonstrated, it is very likely to increase patient safety.…”

Section: Treatment Approachesmentioning

confidence: 99%

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Immunomodulatory treatment of interstitial lung disease

Bosch

Luppi

Ferrara

et al. 2022

Ther Adv Respir Dis

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Interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) have an array of immunomodulatory treatment options compared with IPF, due to their inflammatory component. However, there is a relative paucity of guidance on the management of this heterogeneous group of diseases. In ILDs other than IPF, immunosuppression is the cornerstone of therapy, with varying levels of evidence for different immunomodulatory agents and for each specific ILD. Classification of ILDs is important for guiding treatment decisions. Immunomodulatory agents mainly include corticosteroids, mycophenolate mofetil (MMF), azathioprine, methotrexate, cyclophosphamide and rituximab. In this review, the available evidence for single agents in the most common ILDs is first discussed. We then reviewed practical therapeutic approaches in connective tissue disease–related ILD and interstitial pneumonia with autoimmune features, scleroderma-related ILD, vasculitis and dermatomyositis with hypoxemic respiratory failure, idiopathic non-specific interstitial pneumonia, hypersensitivity pneumonitis sarcoidosis, fibrosing organizing pneumonia and eosinophilic pneumonia. The treatment of acute exacerbations of ILD is also discussed. Therapy augmentation in ILD is dictated by the recognition of progression of disease. Criteria for the evaluation of progression of disease are then discussed. Finally, specific protocol and measures to increase patients’ safety are reviewed as well, including general monitoring and serologic surveillance, Pneumocystis jirovecii prophylaxis, patients’ education, genetic testing for azathioprine, MMF serum levels and cyclophosphamide administration protocols. Immunomodulatory therapies are largely successful in the management of ILDs and can be safely managed with the application of specific protocols, precautions and monitoring.

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Section: Treatment Approachesmentioning

confidence: 98%

Section: Treatment Approachesmentioning

confidence: 99%

Immunomodulatory treatment of interstitial lung disease

Bosch

Luppi

Ferrara

et al. 2022

Ther Adv Respir Dis

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“…Three allelic variants of TPMT, TPMT2, TPMT3A and TPMT3C, account for 80-90% of individuals with low or intermediate TPMT activity [86,87]. International clinical recommendations and guidelines differ on the determination of TPMT status prior to initiation of azathioprine therapy, although regular monitoring of white blood cells is recommended as AEs may be TMPT-independent [39,88]. Patients with RA who are heterozygous for the TPMT3A allele have an increased risk of azathioprine-related haematopoietic and gastrointestinal toxicity compared to those with the wild-type allele [89,90].…”

Section: Safetymentioning

confidence: 99%

“…Taha et al conducted a comparison of the rate of azathioprine discontinuation due to serious AEs in a cohort of patients with ILD who were genotyped (TPMT genotyping) and an untested cohort [88]. The authors found that the overall incidence of AEs was similar between the two cohorts, but the discontinuation rate was significantly lower in the genotyped cohort compared to the untested cohort.…”

Section: Safetymentioning

confidence: 99%

Genomic Profiling for Predictive Treatment Strategies in Fibrotic Interstitial Lung Disease

Perrotta,

Sanduzzi Zamparelli,

D’Agnano

et al. 2024

Biomedicines

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Idiopathic pulmonary fibrosis (IPF) has traditionally been considered the archetype of progressive fibrotic interstitial lung diseases (f-ILDs), but several other f-ILDs can also manifest a progressive phenotype. Integrating genomic signatures into clinical practice for f-ILD patients may help to identify patients predisposed to a progressive phenotype. In addition to the risk of progressive pulmonary fibrosis, there is a growing body of literature examining how pharmacogenomics influences treatment response, particularly regarding the efficacy and safety profiles of antifibrotic and immunomodulatory agents. In this narrative review, we discuss current studies in IPF and other forms of pulmonary fibrosis, including systemic autoimmune disorders associated ILDs, sarcoidosis and hypersensitivity pneumonitis. We also provide insights into the future direction of research in this complex field.

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Purine-based anticancer drugs

Elgemeie,

Mohamed-Ezzat

2022

New Strategies Targeting Cancer Metabolism

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TPMT and HLA-DQA1-HLA-DRB genetic profiling to guide the use of azathioprine in the treatment of interstitial lung disease: First experience

Cited by 3 publications

References 30 publications

Immunomodulatory treatment of interstitial lung disease

Immunomodulatory treatment of interstitial lung disease

Genomic Profiling for Predictive Treatment Strategies in Fibrotic Interstitial Lung Disease

Purine-based anticancer drugs

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