Validation of peptide immunotherapy as a new approach in the treatment of allergic rhinoconjunctivitis: the clinical benefits of treatment with amb a 1 derived t cell epitopes

L16 Validation of Peptide Immunotherapy as a New Approach in L18 Real-world Comparative Effectiveness Of Extrafine the Treatment of Allergic Rhinoconjunctivitis: The Clinical Hydrofluoroalkane-beclomethasone (EF HFA-BDP) Versus Benefits of Treatment with Amb a 1 Derived T cell Epitopes Inhaled Corticosteroid (ICS) / Long-acting Beta-agonist R. P. Hafner1, A. Salapatek2, D. Patel2, M. Larche3, P. Laidler1; 1Circas- sia Limited, Oxford, UNITED KINGDOM, 2Cetero Research, Missis- D. B. Price1,2, R. Martin3, P. Dorinsky4, A. J. Lee1, A. Burden2, J. von Zie- sauga, ON, CANADA, 3McMaster University, Hamilton, ON, CANADA.
genweidt2, A. Chisholm2, E. V. Hillyer2, G. Colice5; 1University of Aber- RATIONALE: A series of T-cell epitopes from cat allergen, Fel d1, deen, Aberdeen, UNITED KINGDOM, 2Research in Real Life, formulated into a short-course peptide vaccine (ToleroMune Cat) was Cambridge, UNITED KINGDOM, 3National Jewish Health, Denver, previously shown to significantly reduce allergic rhinoconjunctivitis symp- CO, 4Teva Pharmaceuticals, Horsham, PA, 5Washington Hospital Center toms shortly after vaccine therapy ended and persistently, one year after and George Washington University School of Medicine, Washington, WA.
dosing start (tolerance). In this study, we evaluated the efficacy of a vaccine RATIONALE: Uncertainty exists around LABA effectiveness in pediatric from a newly identified series of T-cell epitopes from ragweed allergen Amb asthma. We compared the real-world effectiveness of EF HFA-BDP and a1 (ToleroMune Ragweed) on allergic rhinoconjunctivitis symptoms.
ICS/LABA in children stepping-up ICS.
METHODS: Screened ragweed allergic subjects attended four consecu- METHODS: Retrospective study using the UK General Practice and tive 3-hour Baseline Challenges in an Environmental Exposure Chamber Optimum Patient Care Research Databases. Children (4-11 years) stepped- (EEC) where airborne ragweed pollen levels were controlled at 35006500 up existing ICS to (i) higher dose ICS (> grains/m3 . Total Rhinoconjunctivitis Symptom Score (TRSS) was scored (ii) ICS/LABA (no ICS dose/drug change) as fixed-dose combination every 30 minutes on a scale of 0-24. 275 subjects were randomised to pla- (FDC) or free-combination (FC) ICS/LABA. EF HFA-BDP patients were cebo, or one of four ToleroMune Ragweed treatment arms. Subjects re- matched 1:2 (n5325:650) to FC and 1:1 (n5209:209) to FDC patients turned to a series of 4 consecutive, 3-hour Post-Treatment EEC based on demographic and disease characteristics over the pre-step-up Challenges 18-22weeks after the start of treatment.
year. Outcomes evaluated over the post-step-up year included: severe RESULTS: Treatment with ToleroMune Ragweed resulted in the largest exacerbations (ATS/ERS definition); asthma control (no: severe exacer- changes in TRSS in the most symptomatic subjects who had the highest bations; out-of-hours care; outpatient department attendance; antibiotics scores at Baseline. In this group, treatment with the highest dose of for lower respiratory infections); ICS adherence, SABA usage.
ToleroMune Ragweed showed a mean change in the TRSS score at the post RESULTS: There were no significant differences between EF HFA-BDP treatment EEC visit of -5.7765.31 versus a change of -2.9365.31 on and FDC in achieving asthma control (adjusted odds ratio[AOR] 95%CI: placebo (p <0.05). The product was safe and well tolerated.
0.96[0.51-1.80]); exacerbation rates (adjusted rate ratio[ARR] 95%CI: CONCLUSIONS: The efficacy of T cell epitope-based peptide immuno- 1.00 [0.62-1.62]), or odds of higher adherence (0.77 [0.54-1.10]), but odds therapy has been demonstrated for cat and ragweed allergies. This new of higher SABA usage were significantly greater for EF HFA-BDP patients treatment modality offers an exciting alternative short-course immuno- (1.49 [1.07-2.07]). Compared with FC, EF HFA-BDP patients had therapy with an enhanced safety profile that is potentially applicable across significantly higher odds of achieving asthma control (1.50 [1.04-2.16]); with no significant differences in exacerbation rates (0.91 [0.68-1.22]),adherence (EF HFA-BDP: 1.22 [0.95-1.56]) or SABA usage (EF HFA- L17 Sequential IgE-Targeted Therapy Combining Immunapheresis BDP: 1.11 [0.86-1.43]). Median(IQR) doses were 137.0(82.2-219.2)mcg And Omalizumab In Patients With Severe Atopic Dermatitis for EF HFA-BDP vs 82.2(41.1-137.0)mcg fluticasone-equivalent for FDC, And Grossly Elevated Total Serum IgE Levels - A Pilot Trial and 137.0(82.2-219.2)mcg for EF HFA-BDP vs 98.7(65.6-148.0)mcg A. Zink, A. Gensbaur, M. Zirbs, F. Seifert, I. Leon Suarez, J. Liptak, L.
Eichhorn, A. Onken, M. Mempel, J. Huss-Marp, R. Hein, J. Ring, M. Ol- CONCLUSION: Stepping-up ICS as EF HFA-BDP dose increase lert; Department of Dermatology and Allergy, Klinikum rechts der Isar, provides similar asthma control as FDC ICS/LABA therapy and substantial Technische Universit€at M€unchen, Munich, GERMANY.
RATIONALE: To evaluate the role of IgE in atopic dermatitis (AD) bycombining immunoglobulin (Ig)-apheresis and anti-IgE-antibody omali-zumab to reduce IgE in patients with severe, therapy-refractory AD andgrossly elevated IgE levels.
METHODS: Investigator-initiated open-label pilot trial, treating 10patients with Ig-apheresis prior to regular subcutaneous administrationof 450 mg omalizumab every 2 weeks for 6 months followed by a 6 monthsfollow-up. On every visit, total and free IgE and TARC (CCL17) werequantified and the severity of AD documented by standardized photos aswell as rated by SCORAD and by the patients’ personal evaluation on aseverity and pruritus-scale.
RESULTS: Before starting treatment, IgE-levels ranged from 3,728 kU/Lto 69,872 kU/L. IgE-levels were seen to be reduced significantly after theIg-apheresis and to continuously drop in all patients during the anti-IgE-therapy (reaching free IgE levels <150 kU/L in 5/10 and <1,000 kU/L in 9/10 patients). A reverse trend was observed during the follow-up period.
Parallel, a clear improvement of AD was seen during the treatment periodin all patients followed by an aggravation during follow-up (SCORAD,pruritus, severityscale, TARC). Two patients dropped out after initialimprovement due to acute exacerbation despite anti-IgE therapy and onepatient was lost due to lack of compliance.
CONCLUSIONS: The sequential combination of Ig-apheresis andomalizumab is suitable to reduce grossly elevated serum IgE levels andimproves clinical symptoms of severe refractory AD. Due to the limitednumber of patients included and the open-label design in our pilot trial,further studies are needed to strengthen this conclusion.

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