Drug survival of omalizumab in atopic asthma: Impact of clinical and genetic variables

It is estimated that 40-50% of severe asthma has an atopic basis, representing a clinical challenge and a significant economic burden for healthcare systems. The most effective treatment has emerged with the use of biologic therapies such as omalizumab; however, the rate of therapy switching due to loss of efficacy is high, which has a negative impact on the healthcare system. The aim was to evaluate the influence of genetic polymorphisms as predictors of omalizumab survival. We conducted a retrospective observational cohort study of 110 patients with uncontrolled severe allergic asthma treated with omalizumab in a tertiary hospital. We analyzed <i>FCER1A</i> (rs2251746, rs2427837), <i>FCER1B</i> (rs1441586, rs573790, rs1054485, rs569108), <i>C3</i> (rs2230199), FCGR2A (rs1801274), <i>FCGR2B</i> (rs3219018, rs1050501), <i>FCGR3A</i> (rs10127939, rs396991), <i>IL1RL1</i> (rs1420101, rs17026974, rs1921622) and <i>GATA2</i> (rs4857855) by real-time PCR using Taqman probes. Drug survival was defined as the time from initiation to discontinuation of omalizumab. Cox regression analysis adjusted for the presence of respiratory disease, GERD, SAHS and years with asthma showed that the SNPs <i>FCER1B</i> rs573790 - CT (<i>p</i> < .001; HR = 3.38; CI95% = 1.66-6.87), <i>FCGR3A</i> rs10127939-AC (<i>p</i> = .018; HR = 3.85; CI95% = 1.25-11.81) and <i>FCGR3A</i> rs396991-CC (<i>p</i> = .020; HR = 2.23; CI95% = 1.14-4.38) were the independent variables associated with worse survival in patients diagnosed with asthma. A trend toward statistical significance was also found between and <i>FCGR3A</i> rs10127939-CC (<i>p</i> = .080; HR = 0.13; CI95% = 0.01-1.28) and longer drug survival. The results of this study demonstrate the potential influence of the polymorphisms studied on omalizumab survival and the clinical benefit that could be achieved by defining predictive biomarkers of drug survival.