Anti-IL-6 treatment in two pediatric patients with severe persistent asthma with the IL4R576 variant

RATIONALE: The Interleukin-4 receptor alpha chain variant R576 (IL-4Ra-R576) is associated with severe asthma characterized by a mixed T_H2-T_H17 response. Past research demonstrated that treatment of Il4ra^R576 mice with anti-IL-6 antibody protected against severe airway inflammation. We analyzed the response of two patients with severe persistent asthma with the IL4R^R576allelic variant treated with tocilizumab.

METHODS: Patient 1: 6-year-old with severe persistent, non-atopic asthma with homozygous IL4R^R576 variant. He had ongoing severe exacerbations despite ICS/LABA, montelukast, prednisolone, azithromycin, theophylline, and IVIG. He started tocilizumab on 10/2016 at 10mg/kg/dose Q4wks then changed to 8mg/kg/dose Q2wks. Patient 2: 5-year-old with severe persistent, non-atopic asthma with heterozygous IL4R^R576 variant. Patient had ongoing symptoms despite ICS/LABA, montelukast, and prednisolone. He had behavioral side effects with theophylline and lack of benefit with azithromycin. He started tocilizumab on 2/2017 at 10mg/kg/dose Q4wks then changed to 8mg/kg/dose Q2wks.

RESULTS: Patient 1 had one hospital admission (ICU) after starting tocilizumab, a 66.7% reduction in admissions from year prior and 75% reduction from two years prior. FEV₁ increased from 0.9L to 1.16L and C-ACT improved from 21 to 27. Patient 2 had one hospital admission after tocilizumab, a 50% reduction from year prior. FEV₁ increased from 1.22L to 1.33L and was able to discontinue oral steroids. Flow cytometric analysis on patient 1 revealed increased circulating T_H17 and T_H2 cells at baseline that sharply declined following tocilizumab therapy, while those on patient 2 are currently pending.

CONCLUSIONS: Tocilizumab may be an effective therapy for patients with severe persistent asthma associated with the IL4R^R576 allelic variant.