Idiopathic pulmonary fibrosis (IPF) patients with T* alleles of the MUC5B gene or G* alleles of the DSP gene demonstrated increased survival trends with antifibrotic treatment, according to a new study published in Therapeutic Advances in Respiratory Disease.
Compared to patients who did not receive treatment, the study’s results showed, these patient genotypes did not affect the survival of IPF patients as a whole but did contribute to better antifibrotic treatment outcomes.
“Our study has highlighted the contribution of pharmacogenetics to treatment outcomes and may help to identify genetic subgroups likely to benefit from a particular antifibrotic therapy, as desired in the era of precision medicine,” the authors remarked.
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Treatment with antifibrotics (pirfenidone or nintedanib) significantly lowered mortality in IPF patients with a DSP (rs2076295) G* allele genotype compared to those who did not receive antifibrotic treatment (P =.016). Subgroup analysis by genotype showed that G* allele patients responded better to nintedanib (P =.004) when compared to patients with the TT genotype, but outcomes were not different between the 2 groups when given pirfenidone (P =.612).
In contrast, patients with the TT genotype had better overall survival when given pirfenidone compared to nintedanib (P =.033). No difference in mortality was seen between treatment with pirfenidone and nintedanib in patients with G* alleles.
Patients with MUC5B (rs35705950) T* alleles treated with antifibrotics showed a trend toward lower mortality than patients not receiving treatment (P =.079). There was no difference in survival with and without antifibrotic treatment in patients with GG genotypes (P =.678). The study also did not observe a difference between treatment with pirfenidone and nintedanib in the T* allele patients.
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The study also investigated the frequency of DSP and MUC5B alleles in IPF patients compared to healthy control subjects. For DSP rs2076295. where the G allele is generally associated with increased IPF risk, GG genotypes (39.0% vs 18.5%, P <.001) and G* carriers (80.5% vs 68.3%, P <.001) were higher in IPF patients than healthy controls. The presence of G* alleles was also found to be associated with radiological diagnosis (P =.002).
When comparing variants of the MUC5B gene (IPF risk allele T), the GT genotype (50.4% vs 18.5%, P <.001) and T* alleles (55% vs 20.9%, P <.001) were more common in IPF patients compared to controls. No significant difference was found between GG and TT genotypes between groups, however.
For the study, 210 IPF patients (139 men and 71 women) were recruited from the Czech Republic section of the European MultiPartner IPF Registry. Of these, 167 (79.5%) were receiving antifibrotic treatment while the remaining patients were receiving other treatment as they did not meet the criteria for antifibrotic treatment.
A total of 127 patients were receiving pirfenidone compared to 40 on nintedanib. A cohort of 205 healthy controls that matched both age and sex were also recruited for the study (125 men and 80 women).
Reference
Doubkova M, Kriegova E, Littnerova S, et al. DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study. Ther Adv Respir Dis. 2021;15. doi.org/10.1177/17534666211042529
