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Immunization with ARA h1,2,3-Lamp-Vax Peanut Vaccine Blocked IgE Mediated-Anaphylaxis in a Peanut Allergic Murine Model
Abstracts AB167
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Immunization with ARA h1,2,3-Lamp-Vax Peanut Vaccine Blocked IgE Mediated-Anaphylaxis in a Peanut Allergic Murine Model Xiu-Min Li, MD, MS1, Ying Song, MD2, Yan Su3, Teri Heiland3, Hugh A. Sampson, MD1; 1Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 2Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, 3Immunomic Therapeutics Inc, Rockville, MD. RATIONALE: The prevalence, severity and life-long nature of peanut allergy (PNA) lend particular urgency to develop strategies to treat this disease. This study determined the effects of ARA h1,2,3-LAMP-Vax, a peanut vaccine, on peanut allergic mice. METHODS: Five-week-old C3H/HeJ mice were sensitized with 10 mg peanut and 20mg cholera toxin (CT) for 5 weeks and boosted with 50 mg peanut and 20mg CT at weeks 6 and 8. Mice with established PNA were treated with ARA h1,2,3-LAMP-Vax or control vector intradermally (i.d.), weekly for 4 weeks. Three weeks post- therapy, mice were challenged intragastrically with peanut. Anaphylactic reactions, plasma histamine, peanut-specific IgE levels, and cultured splenocyte (SPC) and mesenteric lymph node (MLN) cell cytokine production were measured. RESULTS: Prior to treatment, there was no significant difference in serum peanut-specific IgE levels between peanut sensitized groups. Three weeks post therapy, ARA h1,2,3-LAMP Vax treated mice exhibited approximately 70% lower serum peanut-specific IgE levels than vector control treated mice (2,911.3 Vs 887.9ng/ml, p<0.05). ARA h1,2,3-LAMP-Vax treatment increased peanut-specific IgG2a (p<0.05), but not IgG1 levels. ARA h1,2,3-LAMP-Vax -treated mice also showed significantly lower symptom scores, higher core body temperatures and lower plasma histamine levels following challenge than control vector-treated mice (p<0.05 for all). SPCs and MLN cells from ARA h1,2,3-LAMP-Vaxtreated mice produced less IL-4 and more IFN-g and IL-10 than cells from control vector-treated mice. CONCLUSIONS: ARA h1,2,3-LAMP-Vax administration produced significant protection against peanut induced anaphylactic reactions in peanut allergic mice. This study shows that ARA h1,2,3-LAMP-Vax has potential as a novel therapy for peanut allergy.
543
Clinical and Immunological Effects of Aspirin Desensitization in Patients with Aspirin Exacerbated Respiratory Diseases; A Randomized, Double Blind, Placebo Controlled Trial Hossein Esmaeilzadeh, MD1,2, Mohammad Nabavi3, Saba Arshi4, Mohammad Hassan Bemanian5, Morteza Fallahpour5, Zahra Aryan6; 1 Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran, Tehran, 22- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran, 3Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran, Iran, 4Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran, 5Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehan University of Medical Sciences, Tehran, Iran, 6Molecular Immunology Research Center; and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. RATIONALE: The effect of aspirin desensitization (AD) on clinical and immunological profile of patients with aspirin exacerbated respiratory diseases (AERD) has been poorly understood. METHODS: This randomized double blind placebo controlled trial comprised of 32 adult patients with AERD (NCT01867281). Participants were randomly assigned to equal ratio active and placebo groups. Active group underwent AD over a 2-day period with increasing doses of aspirin (ketorolac sprays, 60, 125, 325 and 625 mg) and followed by receiving aspirin 625 mg twice daily for 1 month and 625 mg for 5 months. Frequency of asthma attacks, Sino-Nasal Outcome Test (SNOT22) scores, pulmonary function tests, Lund Mackay scores, medication scores, and serum levels of interleukin (IL)-10, transforming growth factor beta (TGF-
b) and interferon gamma (IFN-g) were investigated at baseline and end of first and sixth months of follow up. RESULTS: Symptoms scores and medication needs of patients with AERD underwent AD were significantly lower compared to placebo group after 6 months (7.563.5 vs. 10.663.8 and 9.36 2.0 vs. 11.063.1, respectively, all p<0.05). Forced expiratory volume in one second (FEV1) was significantly higher in active arm after 6 months16.6.8 vs. 80.1 6 7.4, p50.009).Frequency of asthma attacks was lower in active versus placebo group(25% versus 50%, p50.137).However, no significant difference was observed in serum concentration of IL-10, IFN-g and TGFb between two groups neither at baseline nor at the end of study. CONCLUSIONS: The clinical benefits of AD on patients with AERD are not coupled with any significant change in systemic anti-inflammatory regulation markers.
544
Dupilumab Improves Patient-Reported Outcomes (PROs) in a Phase 2 Study in Adults with Moderate-to-Severe Atopic Dermatitis Eric Simpson, MD, MCR1, Margitta Worm, MD2, Weily Soong, MD, FAAAAI3, Andrew Blauvelt, MD, MBA4, Laurent Eckert5, Richard Wu, PhD6, Marius Ardeleanu, MD6, Neil Graham, MD6, Gianluca Pirozzi, MD, PhD7, E. Rand Sutherland, MD, MPH8, Vera Mastey6; 1 OHSU, Portland, OR, 2Charite - Universit€atsmedizin Berlin, Berlin, Germany, 3Alabama Allergy & Asthma Center, Birmingham, AL, 4Oregon Medical Research Center, Portland, OR, 5Sanofi, Paris, France, 6Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 7Sanofi, Bridgewater, NJ, 8Sanofi, Cambridge, MA. RATIONALE: Atopic dermatitis (AD) is associated with substantial patient burden. Dupilumab, a fully-human monoclonal antibody against the interleukin-4 receptor-a, has demonstrated symptomatic efficacy in AD. METHODS: 380 adults with moderate-to-severe AD were randomized 1:1:1:1:1:1 to 16-week treatment with subcutaneous placebo or dupilumab 100mg every 4 weeks (q4w), 300mg-q4w, 200mg every 2 weeks (q2w), 300mg-q2w, or 300mg weekly (NCT01859988). Assessments included PROs of Pruritus Numeric Rating Scale (NRS), SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), Dermatology Life Quality Index (DLQI), and EuroQol-5D (EQ-5D). RESULTS: Mean age was 37 years; mean disease duration was 28 years. At 16 weeks, dupilumab significantly reduced itch on NRS (>3-point decrease) in 20% to 54% of patients vs. 8.2% in placebo group (P<0.0005 all doses except 100mg-q4w P<0.05), along with improvements in sleep on items of SCORAD and POEM measures (P<0.0005 all doses except 100mg-q4w). Dupilumab also significantly reduced symptoms of depression and anxiety on HADS; number of patients with scores >11 indicating probable cases of anxiety or depression decreased by 66.7% to 75% in dupilumab groups vs. 22.2% in placebo group (P<0.05 all doses). Quality of life (QOL) improved at all dupilumab doses except 100mg-q4w (DLQI, P<0.0001; and EQ-5D, P<0.05). The most common adverse events (dupilumab doses combined vs. placebo) were nasopharyngitis (20.6% vs. 21.3%), headache (11.1% vs. 3.3%), and injection site reaction (9.5% vs. 3.3%). CONCLUSIONS: In adults with moderate-to-severe AD, dupilumab significantly reduced patient-reported itch relative to placebo, with concomitant improvements on PROs that evaluated sleep, mood, and QOL.
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J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Immunization with ARA h1,2,3-Lamp-Vax Peanut Vaccine Blocked IgE Mediated-Anaphylaxis in a Peanut Allergic Murine Model Xiu-Min Li, MD, MS1, Ying Song, MD2, Yan Su3, Teri Heiland3, Hugh A. Sampson, MD1; 1Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 2Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, 3Immunomic Therapeutics Inc, Rockville, MD. RATIONALE: The prevalence, severity and life-long nature of peanut allergy (PNA) lend particular urgency to develop strategies to treat this disease. This study determined the effects of ARA h1,2,3-LAMP-Vax, a peanut vaccine, on peanut allergic mice. METHODS: Five-week-old C3H/HeJ mice were sensitized with 10 mg peanut and 20mg cholera toxin (CT) for 5 weeks and boosted with 50 mg peanut and 20mg CT at weeks 6 and 8. Mice with established PNA were treated with ARA h1,2,3-LAMP-Vax or control vector intradermally (i.d.), weekly for 4 weeks. Three weeks post- therapy, mice were challenged intragastrically with peanut. Anaphylactic reactions, plasma histamine, peanut-specific IgE levels, and cultured splenocyte (SPC) and mesenteric lymph node (MLN) cell cytokine production were measured. RESULTS: Prior to treatment, there was no significant difference in serum peanut-specific IgE levels between peanut sensitized groups. Three weeks post therapy, ARA h1,2,3-LAMP Vax treated mice exhibited approximately 70% lower serum peanut-specific IgE levels than vector control treated mice (2,911.3 Vs 887.9ng/ml, p<0.05). ARA h1,2,3-LAMP-Vax treatment increased peanut-specific IgG2a (p<0.05), but not IgG1 levels. ARA h1,2,3-LAMP-Vax -treated mice also showed significantly lower symptom scores, higher core body temperatures and lower plasma histamine levels following challenge than control vector-treated mice (p<0.05 for all). SPCs and MLN cells from ARA h1,2,3-LAMP-Vaxtreated mice produced less IL-4 and more IFN-g and IL-10 than cells from control vector-treated mice. CONCLUSIONS: ARA h1,2,3-LAMP-Vax administration produced significant protection against peanut induced anaphylactic reactions in peanut allergic mice. This study shows that ARA h1,2,3-LAMP-Vax has potential as a novel therapy for peanut allergy.
543
Clinical and Immunological Effects of Aspirin Desensitization in Patients with Aspirin Exacerbated Respiratory Diseases; A Randomized, Double Blind, Placebo Controlled Trial Hossein Esmaeilzadeh, MD1,2, Mohammad Nabavi3, Saba Arshi4, Mohammad Hassan Bemanian5, Morteza Fallahpour5, Zahra Aryan6; 1 Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran, Tehran, 22- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran, 3Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran, Iran, 4Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran, 5Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehan University of Medical Sciences, Tehran, Iran, 6Molecular Immunology Research Center; and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. RATIONALE: The effect of aspirin desensitization (AD) on clinical and immunological profile of patients with aspirin exacerbated respiratory diseases (AERD) has been poorly understood. METHODS: This randomized double blind placebo controlled trial comprised of 32 adult patients with AERD (NCT01867281). Participants were randomly assigned to equal ratio active and placebo groups. Active group underwent AD over a 2-day period with increasing doses of aspirin (ketorolac sprays, 60, 125, 325 and 625 mg) and followed by receiving aspirin 625 mg twice daily for 1 month and 625 mg for 5 months. Frequency of asthma attacks, Sino-Nasal Outcome Test (SNOT22) scores, pulmonary function tests, Lund Mackay scores, medication scores, and serum levels of interleukin (IL)-10, transforming growth factor beta (TGF-
b) and interferon gamma (IFN-g) were investigated at baseline and end of first and sixth months of follow up. RESULTS: Symptoms scores and medication needs of patients with AERD underwent AD were significantly lower compared to placebo group after 6 months (7.563.5 vs. 10.663.8 and 9.36 2.0 vs. 11.063.1, respectively, all p<0.05). Forced expiratory volume in one second (FEV1) was significantly higher in active arm after 6 months16.6.8 vs. 80.1 6 7.4, p50.009).Frequency of asthma attacks was lower in active versus placebo group(25% versus 50%, p50.137).However, no significant difference was observed in serum concentration of IL-10, IFN-g and TGFb between two groups neither at baseline nor at the end of study. CONCLUSIONS: The clinical benefits of AD on patients with AERD are not coupled with any significant change in systemic anti-inflammatory regulation markers.
544
Dupilumab Improves Patient-Reported Outcomes (PROs) in a Phase 2 Study in Adults with Moderate-to-Severe Atopic Dermatitis Eric Simpson, MD, MCR1, Margitta Worm, MD2, Weily Soong, MD, FAAAAI3, Andrew Blauvelt, MD, MBA4, Laurent Eckert5, Richard Wu, PhD6, Marius Ardeleanu, MD6, Neil Graham, MD6, Gianluca Pirozzi, MD, PhD7, E. Rand Sutherland, MD, MPH8, Vera Mastey6; 1 OHSU, Portland, OR, 2Charite - Universit€atsmedizin Berlin, Berlin, Germany, 3Alabama Allergy & Asthma Center, Birmingham, AL, 4Oregon Medical Research Center, Portland, OR, 5Sanofi, Paris, France, 6Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 7Sanofi, Bridgewater, NJ, 8Sanofi, Cambridge, MA. RATIONALE: Atopic dermatitis (AD) is associated with substantial patient burden. Dupilumab, a fully-human monoclonal antibody against the interleukin-4 receptor-a, has demonstrated symptomatic efficacy in AD. METHODS: 380 adults with moderate-to-severe AD were randomized 1:1:1:1:1:1 to 16-week treatment with subcutaneous placebo or dupilumab 100mg every 4 weeks (q4w), 300mg-q4w, 200mg every 2 weeks (q2w), 300mg-q2w, or 300mg weekly (NCT01859988). Assessments included PROs of Pruritus Numeric Rating Scale (NRS), SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), Dermatology Life Quality Index (DLQI), and EuroQol-5D (EQ-5D). RESULTS: Mean age was 37 years; mean disease duration was 28 years. At 16 weeks, dupilumab significantly reduced itch on NRS (>3-point decrease) in 20% to 54% of patients vs. 8.2% in placebo group (P<0.0005 all doses except 100mg-q4w P<0.05), along with improvements in sleep on items of SCORAD and POEM measures (P<0.0005 all doses except 100mg-q4w). Dupilumab also significantly reduced symptoms of depression and anxiety on HADS; number of patients with scores >11 indicating probable cases of anxiety or depression decreased by 66.7% to 75% in dupilumab groups vs. 22.2% in placebo group (P<0.05 all doses). Quality of life (QOL) improved at all dupilumab doses except 100mg-q4w (DLQI, P<0.0001; and EQ-5D, P<0.05). The most common adverse events (dupilumab doses combined vs. placebo) were nasopharyngitis (20.6% vs. 21.3%), headache (11.1% vs. 3.3%), and injection site reaction (9.5% vs. 3.3%). CONCLUSIONS: In adults with moderate-to-severe AD, dupilumab significantly reduced patient-reported itch relative to placebo, with concomitant improvements on PROs that evaluated sleep, mood, and QOL.
SUNDAY
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