346:
Anti-IL-6 treatment in two pediatric patients with severe persistent asthma with the IL4R576 variant
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Brittany Esty, MD, Lisa M. Bartnikas, MD, Louis M. Charbonnier, PhD, Amir Hossein Massoud, PhD, Carmen Leon-Astudillo, MD, Gary Visner, DO, Meera Subramaniam, MD, Wanda Phipatanakul, MD MS FAAAAI, Talal A. Chatila, MD MSc
RATIONALE: The Interleukin-4 receptor alpha chain variant R576 (IL-4Ra-R576) is associated with severe asthma characterized by a mixed TH2-TH17 response. Past research demonstrated that treatment of Il4raR576 mice with anti-IL-6 antibody protected against severe airway inflammation. We analyzed the response of two patients with severe persistent asthma with the IL4RR576allelic variant treated with tocilizumab.

METHODS: Patient 1: 6-year-old with severe persistent, non-atopic asthma with homozygous IL4RR576 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 IL4RR576 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 TH17 and TH2 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 IL4RR576 allelic variant.