Background The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are three discrete entities – Granulomatosis with polyangiitis (GPA), Microscopic polyangiitis (MPA), and Eosinophilic granulomatosis with polyangiitis (EGPA). They present with a plethora of signs and symptoms resulting in significant burden of mortality and morbidity. There is huge lacuna in the knowledge of relationship between various genes affecting pharmacogenetics of AAV and its implications in context of therapeutic complications. We thus intend to evaluate genotypic polymorphism in FcγR family & CYP genes affecting pharmaco-biological response of Rituximab and Cyclophosphamide respectively in AAV patients undergoing induction treatment.

Objectives To study the single nucleotide polymorphism (SNP) of the FcγR family (FcγRIIIA, FcγRIIA, FcγRIIB) in patients receiving Rituximab (RTX) and the SNPs of CYP2C19*2 (rs4244285), CYP2B6 (rs321137) polymorphisms in patients receiving Cyclophosphamide (CYC) using polymerase chain reaction. Additionally, to correlate the genetic polymorphism of AAV patients with Rituximab and Cyclophosphamide treatment response.

Methods This study was a prospective cohort study in which AAV patients undergoing induction treatment were enrolled from Jan 2021 to Dec 2022 in Clinical Rheumatology Department at PGIMER Chandigarh, India. Functional SNPs for FcγR(FcγRIIb 695T>C, FcγRIIIa 559T>G and FcγRIIa 519G>A) and CYP enzymes (CYP2C19 681G>A, CYP2B6 1459C>T) were assesed by Sanger sequencing of PCR amplified genomic DNA. The end points were to detect associations between the tested SNPs and status of remission at six months and complete remission at end of the study.

Results In this study we recruited ninty seven patients of AAV in Indian population. Table 1 summarises the baseline clinical characterisitics of the study population. FcγRIIA variant (v) allele frequency was more than wild allele (W) frequency in the study population. The time to achieve remission was significantly lower (mean:9.22 weeks) in FcγRIIA variant genotype polymorphism (FcγRIIa 519AA) in comparison to wild and heterozygotes variants (mean: 17.25 weeks) of FcγRIIA at site 131 (519G>A), as shown in Figure1. There were no significant difference observed in CYP polymorphism and cyclophosphamide response.

Conclusion This study is one of the first to evaluate the pharmacogenomic profile of AAV in Indian population. We observed highly significant association of SNPs of FcγRIIa 131 site variant/519AA genotype with early remission and complete remission after induction treatment with rituximab. This data could further help in tailored treatment of AAV patients and may also serve as a prognostic marker.

References [1]Cartin-Ceba R, Indrakanti D, Specks U, et al. The Pharmacogenomic Association of Fcγ Receptors and Cytochrome P450 Enzymes With Response to Rituximab or Cyclophosphamide Treatment in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis. Arthritis Rheumatol. 2017;69(1):169–75.

[2]Lee YH, Bae S-C, Song GG. Functional FCGR3A 158 V/F and IL-6 -174 C/G polymorphisms predict response to biologic therapy in patients with rheumatoid arthritis: a meta-analysis. Rheumatol Int. 2014 Oct;34(10):1409–15.

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Acknowledgements: NIL.

Disclosure of Interests None Declared.