3. Asthme et immunothérapie sublinguale (SLIT)

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1 Dr. Guillaume Buss Service d immunologie et allergie, CHUV Formation continue «asthme et allergies» Lausanne, le 8 octobre 2015

2 1. Historique 2. Asthme et immunothérapie sous-cutanée (SCIT) 1. Mécanismes 2. Indications 3. Efficace? 4. Préventif? 5. Safety? 6. Cost-effective? 3. Asthme et immunothérapie sublinguale (SLIT) 4. Perspectives

3 Lancet, juin 1911

4 Gaillard J et al. Rev Med Suisse 2011; 7: 850-5

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6 Gaillard J et al. Rev Med Suisse 2011; 7: 850-5

7 Suivi clinique de 10 ans ( ): patients traités par immunothérapie (SCIT) patients traités par anti-h1 + corticoïde topique. Patients sous immunothérapie: - Incidence diminuée de la mortalité (HR 0.71, 95% CI). - Incidence diminuée d infarctus du myocarde (HR 0.70, 95% CI) et de cardiopathie ischémique (HR 0.88, 95% CI) - Incidence diminuée des maladies auto-immunes (HR 0.86, 95% CI)

8 Walker SM, Durham R et al. J Allergy Clin Immunol 2001;107:87-93 Double-blind, randomized, placebo-controled, parallel group study 44 patients with severe summer hay fever: - 36 with seasonal chest symptoms - 28 with seasonal BHR Results : Significant reductions in the SIT group in: - Asthma symptom score (90%, 11%; P < 0.05) - Impairment of overall QOL was less in SIT group ( P = 0.02)

9 Walker SM, Durham R et al. J Allergy Clin Immunol 2001;107:87-93

10 (n = 33) (Fluticasone, n = 32) - Sixty-five children with asthma and dust mite hypersensitivity (Global Initiative for Asthma treatment levels II and III; 6-17 years old) - IT group (DM allergoid SCIT): mean daily dose decreased from ug in the baseline period to ug after 2 years of treatment - Control group: mean daily dose decreased from ug to ug Zielen S et al. JACI 2010;126:942-9

11 35 études : 12 (acariens): (pollens): (autres): études : 12 (acariens): (pollens): (autres):

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13 Möller C. et al. J Allergy Clin Immunol 2002;109:251-6 Jacobsen L et al. Allergy 2007: 62: children aged 6 to 14 years with grass and/or birch pollen allergy - 20% of the children with mild asthma symptoms during pollen season before start of IT

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15 Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study. 138 italian children (age range 5±8 years), intermittent asthma with or without rhinitis, monosensitization to DM Pajno GB et al. Clinical and Experimental Allergy, 2001, Volume 31,

16 Rhinitis SIT Severity score Asthma

17 76 SCIT-related FRs occuring between 1945 and 2001 in North America.

18 : 18.9 million injection visits. NO SCIT-related FR Epstein DG, Bernstein DI et al. Ann Allergy Asthma Immunol 2013; (110):

19 Percentage of practice routinely adjusting doses during the peak pollen seasons and severity of SRs Severity of systemic reactions (SRs) for different types of subcutaneous immunotherapy build-up regimens (conventional, cluster, and rush). Epstein DG, Bernstein DI et al. Ann Allergy Asthma Immunol 2013; (110):

20 SCIT for 3 years in patients allergic to pollen or mites (±asthma) Symptoms inadequately controlled by symptomatic treatment After 10 years, the administration of SIT is economically advantageous (Germany) Schädlich PK et al. Pharmacoeconomics, 2000, 17 (1):37-52

21 Cox L et al. Curr Opin Otolaryngol Head Neck Surg 2015, 23:

22 Advantages Effective Preventive Cost effective Active on multiple organs Etiological Of long duration after discontinuation Disadvantages Duration of therapy Secondary effects

23 Advantages of SLIT (vs SCIT) Non invasive More acceptable in children? Safer Home administration Unique potential interest Directed against allergy induction sites (mucosal surfaces)

24 Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: A randomized, double-blind, placebo-controlled trial Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma (budesonide) Mosbech H et al. J Allergy Clin Immunol 2014;134:568-75

25 Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method Calamita Z et al. Allergy 2006; 61: Overall asthma parameter improvement (asthmatic symptoms, respiratory function test, symptom relief medication, lung reactivity) - No statistical significance if parameters taken separately

26 Casale TB et al. J Allergy Clin Immunol 2014;133:612-9

27 TRSS = total rhino- conjunctivitis symptom score Patel D et et al. J Allergy Clin Immunol 2013;131:103-9

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29 Good evidence for an interest of SCIT in asthma treatment and prevention Still debatable evidence for an interest of SLIT in asthma treatment and prevention Open future for alternative immunotherapy strategies