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Curr Opin Pulm Med. 2020 Mar 19. doi: 10.1097/MCP.0000000000000681. [Epub ahead of print]

Pharmacogenetics of antitumor necrosis factor therapy in severe sarcoidosis.

Author information

1
Department of Pulmonology, Interstitial Lung Diseases Center of Excellence, St. Antonius Hospital, Nieuwegein.
2
Department of Clinical Pharmacy, Division of Laboratories Pharmacy, and Biochemical Genetics, University Medical Center Utrecht, Utrecht.
3
Department of Clinical Chemistry, Interstitial Lung Diseases Center of Excellence, St. Antonius Hospital, Nieuwegein.
4
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University.
5
Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.

Abstract

PURPOSE OF REVIEW:

Antitumor necrosis factor (TNF) treatment is an effective third-line treatment option in severe sarcoidosis. But not all patients respond to treatment. Pharmacogenetics studies the influence of genetic variations on treatment response.

RECENT FINDINGS:

In sarcoidosis, only one study reported on a relationship between genetic variation in TNF and response to anti-TNF therapy. In immune-mediated inflammatory diseases (IMIDs) other than sarcoidosis, several genetic variants were associated with response to anti-TNF therapy. Genes related to TNF, the target of this group of drugs, and the pathway by which TNF exerts its effect, TNF receptor, were studied most extensively. Recent findings related genetic variations in the human leukocyte antigen region to development of antidrug antibodies.We also included new original data on genetic variations and response to anti-TNF therapy in severe sarcoidosis. We found that TNFRSF1A rs1800693 AA genotype, TNFRSF1B 196T and absence of HLA-DRB103 associate with better response after infliximab treatment in severe sarcoidosis.

SUMMARY:

Data on pharmacogenetics of anti-TNF therapy in severe sarcoidosis are scarce. Findings in other IMIDs indicate there may be a role for pharmacogenetics in predicting response and adverse events in anti-TNF therapy, also in sarcoidosis. Future studies are needed to evaluate pharmacogenetics as a predicting marker in anti-TNF therapy in sarcoidosis.

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