1. © 2008 Universitair Ziekenhuis Gent1 ARIA-guidelines, an update Van Cauwenberge P, MD, PhD Van Hoecke H, MD Philippe Gevaert, MD, PhD Department of Otorinolaryngology Ghent University, Belgium

2. 2 2© 2008 Universitair Ziekenhuis Gent Allergic rhinitis: treatment modalities From Diamant Z

3. 3 3© 2008 Universitair Ziekenhuis Gent allergen avoidance indicated when possible allergen avoidance indicated when possible pharmacotherapy safety effectiveness easy to be administered pharmacotherapy safety effectiveness easy to be administered immunotherapy effectiveness specialist prescription may alter the natural course of the disease immunotherapy effectiveness specialist prescription may alter the natural course of the disease patient's education always indicated patient's education always indicated COSTS Cornerstones of AR treatment

4. 4 4© 2008 Universitair Ziekenhuis Gent Clinical guidelines ‘Clinical guidelines are systematically developed statements to assist practioners and patients in making decisions about appropriate and effective health care in specific circumstances.’ Jackson R, et al. BMJ 1998

5. 5 5© 2008 Universitair Ziekenhuis Gent 199420011996, 19982000 Opinion-based guidelines Evidence-based guidelines Guidelines for allergic rhinitis 2008

6. 6 6© 2008 Universitair Ziekenhuis Gent Allergy 1994;49:1-34 V.J. Lund D. Aaronson J. Bousquet R. Dahl R.J. Davies S. Durham R. Gerth van Wijk K. Holmberg E. Juniper Ian S. Mackay L. Malm N. Mygind M. Okuda C. Ortolani H.M. Schanker S.L. Spector P. van Cauwenberge M.R. Wayoff International Consensus Report 1994

7. 7 7© 2008 Universitair Ziekenhuis Gent Scan pag 28 International Consensus Report: Flow Chart

8. 8 8© 2008 Universitair Ziekenhuis Gent D. Skoner M. Dykewicz S. Fineman R. Nicklas R. Lee J. Blessing-Moore Ann All Asthma Immunol 1998; 81:478-518 J. Li I. Bernstein W. Berger S. Spector D. Schuller American Guidelines on Rhinitis 1998

9. 9 9© 2008 Universitair Ziekenhuis Gent P. van Cauwenberge C. Bachert J. Bousquet G. Canonica S. Durham W. Fokkens P. Howarth Allergy 2000;55:116-134 V Lund N. Mygind G. Passalacqua D. Passali G. Scadding D. Wang EAACI Position Paper 2000

10. 10 © 2008 Universitair Ziekenhuis Gent Nasal Corticosteroids Inadeq. control Inadeq. control Inadeq. control Need for therapy ? Mild disease or occasional symptoms Moderate disease or long duration Severe disease Oral or Nasal Antihistamines (Cromones) Nasal Corticosteroids + Oral or Nasal Antihistamines Add further symptomatic treatment Short-course Oral Steroids Consider Immunotherapy For eye symptoms : topical antihistamines or cromones Seasonal allergic rhinitis

11. 11 © 2008 Universitair Ziekenhuis Gent Perennial allergic rhinitis in adults Inadeq. control Need for therapy ? Avoidance Environment control Moderate disease or long duration Severe symptoms Oral or Nasal Antihistamines Nasal Corticosteroids Nasal Corticosteroids + Antihistamines Inadeq. control Further examinations Inadeq. control Mild disease or occasional symptoms

12. 12 © 2008 Universitair Ziekenhuis Gent Perennial allergic rhinitis in adults If resistant RESISTANT CASES Resistant rhinorrhea Short Course of Topical Decongestants/ Oral Decongestants/ Oral Steroids Nasal Ipratropium bromide Immunotherapy Nasal blockage Surgical turbinate reduction

13. 13 © 2008 Universitair Ziekenhuis Gent J. Bousquet P. van Cauwenberge N. Khaltaev N. Ait-Khaled I. Annesi-Maesano C. Bachert C. Baena-Cagnani E. Bateman S. Bonini G. Canonica K. Carlsen P. Demoly S. Durham D. Enarson W. Fokkens R. Gerth van Wijk P. Howarth N. Ivanova J. Kemp J. Klossek R. Lockey V. Lund I. MacKay H. Malling E. Meltzer N. Mygind M. Okuda R. Pawankar D. Price G. Scadding F. Simons A. Szczeklik E. Valovirta A. Vignola D. Wang J. Warner K. Weiss ARIA 2001 In collaboration with WHO JACI 2001;108 (Suppl 5):S147-S333

14. 14 © 2008 Universitair Ziekenhuis Gent Patients with (persistent) AR should be evaluated for asthma Patients with (persistent) asthma should be evaluated for AR A combined strategy should be developed to treat co-existing diseases of the upper and lower airways Combined approach for AR and asthma

15. 15 © 2008 Universitair Ziekenhuis Gent Changed classification for AR Moderate-severe one or more items. abnormal sleep. impairment of daily activities, sport, leisure. abnormal work and school. troublesome symptoms Persistent. > 4 days per week. and > 4 weeks Mild normal sleep & no impairment of daily activities, sport, leisure & normal work and school & no troublesome symptoms Intermittent.  4 days per week. or  4 weeks in untreated patients

16. 16 © 2008 Universitair Ziekenhuis Gent Persistent33%Persistent33% Intermittent67%Intermittent67% N=1,265 subjects with physician-based diagnosis SAR: symptoms restricted to spring and/or summer N=1,265 subjects with physician-based diagnosis SAR: symptoms restricted to spring and/or summer PAR51%PAR51% SAR49%SAR49% SAR/PAR ARIA study step 1 (N=1,230) Prevalences are different Bauchau et al, Eur Respir J 2004

17. 17 © 2008 Universitair Ziekenhuis Gent Classification of AR Patients in General Practice during Pollen Season N=804 subjects with GP-based diagnosis Van Hoecke et al, 2005 persistent Intermittent Mod/Sev 2% 9% 55% Mild 33%

18. 18 © 2008 Universitair Ziekenhuis Gent Van Hoecke et al, 2005 NS N=351 subjects with GP-based diagnosis, responsible allergens confirmed by allergy testing Responsible Allergens in Persistent vs Intermittent AR

19. 19 © 2008 Universitair Ziekenhuis Gent Symptom Severity in Persistent vs Intermittent AR N=804 subjects with GP-based diagnosis Van Hoecke et al, 2005 IntermittentPersistentp value Runny nose59.159.3NS Blocked nose 58.466.20.03 Itchy nose50.243.80.09 Sneezing61.962.4NS Conjunctivitis37.4 43.8 0.09 Severity of each symptom is measured on a scale 1-4, expressed as % with score 3 or 4 - N=804 Headache11.715.50.1 Somnolence6.813.80.002

20. 20 © 2008 Universitair Ziekenhuis Gent Burden of Persistent Rhinitis N=804 subjects with GP-based diagnosis Van Hoecke et al, 2005 IntermittentPersistentp value 33.543.40.006 69.873.8NS 51.456.6NS 73.584.8<0.001 Impaired sleep Impaired activities/sports/leisure Impaired school/work Troublesome symptoms Moderate/severe AR86.694.10.001 % Allergy testing44.269.3<0.001 Specialist referral7.012.40.01

21. 21 © 2008 Universitair Ziekenhuis Gent Persistent AR Has Specific Clinical Characteristics T5SS (from 0 to 15): 8.97 (2.27)* RQLQ (from 0 to 6): 3.04 (0.93)* Loss of 17.9 work days per patient per year ** On co-morbidity = asthma, sinusitis, otitis media, upper respiratory infections: 11.8 events per month per 100 patients ** 10% mild vs 90% moderate Severe allergic rhinitis: Mild –moderate –severe subgroups? Validation ARIA

22. 22 © 2008 Universitair Ziekenhuis Gent Ia Evidence from meta-analysis of randomised controlled trials Ib Evidence from at least one randomised controlled trial IIaEvidence from at least one controlled study without randomisation IIbEvidence from at least one other type of quasi-experimental study IIIEvidence from non-experimental descriptive studies, such as comparative studies, correlation studies and case-control studies IVEvidence from expert committee reports or opinions or clinical experience of respected authorities, or both A B C D Shekelle et al, BMJ 1999 Evidence-based recommendations

23. 23 © 2008 Universitair Ziekenhuis Gent Strength of evidence for rhinitis treatments InterventionSAR Adult SAR Children PAR Adult PAR Children Oral anti-H1AAAA Nasal anti-H1AAAA Nasal CSAAAA Nasal cromoneAAAA AntileukotrieneAA Subcut SITAAAA Subling/nasal ITAAA Allergen avoidanceDDDD

24. 24 © 2008 Universitair Ziekenhuis Gent mild intermittent mild persistent moderate severe intermittent moderate severe persistent allergen and irritant avoidance immunotherapy intra-nasal decongestant (<10 days) or oral decongestant local cromone intra-nasal steroid oral or local non-sedative H1-blocker Stepwise rhinitis treatment

25. 25 © 2008 Universitair Ziekenhuis Gent ARIA 2008 In collaboration with WHO, Ga2len and AllerGen Allergy 2008; 63(Suppl 86):8-160 J. Bousquet N. Khaltaev A. Cruz J. Denburg W. Fokkens A. Togias T. Zuberbier C. Baena-Cagnani G. Canonica C. van Weel I. Agache N. Khaled C. Bachert M. Blaiss S. Bonini L. Boulet P. Bousquet P. Camargos K. Carlsen Y. Chen A. Custovic B. Dahl P. Demoly H. Douagui S. Durham R. Gerth van Wijk O. Kalayci M. Kaliner Y. Kim M. Kowalski P. Kuna L. Le C. Lemiere J. Li R. Lockey S. Mavale-Manuel E. Meltzer Y. Mohammad J. Mullol R. Naclerio R. Hehir K. Ohta S. Ouedraogo S. Palkonen N. Papadopoulos G. Passalacqua R. Pawankar T. A. Popov K.Rabe J. Rosado-Pinto G. Scadding F. Simons E. Toskala E. Valovirta P. Van Cauwenberge D.-Y. Wang M. Wickman B. Yawn A. Yorgancioglu A. Yusuf A. Zar

26. 26 © 2008 Universitair Ziekenhuis Gent International Consensus 1994 EAACI 2000ARIA 2001ARIA 2008 Nr of members (should be between 6 & 15 (Shekelle, 1999)  (18) OK (14)  (37)  (61) + 35 reviewers Composition of group ENT-All: OK No GP’s ENT-All: OK No GP’s OK Countries1171734 Continents3245 Gender (M/F)16/212/230/746/15 University vs non-university 16/214/0 34/353/8 Conflict of interest (pharmaceutical industry) Not mentioned Not mentioned Not specified who Specified Expert panel for guideline development

27. 27 © 2008 Universitair Ziekenhuis Gent Need for ARIA update Increasing knowledge on epidemiology, diagnosis, management and comorbidities of AR since 1999 Need for validation of ARIA classification and management recommendations Availability of new evidence-based systems to guide recommendations, including safety, costs and efficacy of treatments Need to address previous gaps in knowledge (e.g. complementary and alternative medicine) 2008 Update

28. 28 © 2008 Universitair Ziekenhuis Gent Strength of evidence for rhinitis treatments InterventionSAR Adult SAR Children PAR Adult PAR Children PER Oral anti-H1AAAAA Nasal anti-H1AAAAA* Nasal GCSAAAAA* Nasal cromoneAAAAA* AntileukotrieneAA (>6y)AAA* Subcut SITAAAA Sublingual SITAAAA Anti-IgEAA (>12y)AA HomeopathyDDDD AccupunctureDDDD PhytotherapyBDDD Allergen avoidanceDDDD 2008 Update Indirect evidence*

29. 29 © 2008 Universitair Ziekenhuis Gent mild intermittent mild persistent moderate severe intermittent moderate severe persistent allergen and irritant avoidance immunotherapy intra-nasal decongestant (<10 days) or oral decongestant local cromone intra-nasal steroid oral or local non-sedative H1-blocker or anti-leukotriene Stepwise rhinitis treatment 2008 Update

30. 30 © 2008 Universitair Ziekenhuis Gent MeasureEvidence of effect on allergen levelsEvidence of clinical benefit HOUSE DUST MITES Encase bedding in impermeable coversSome None (adults): Evidence A Some (children): Evidence B Wash bedding on a hot cycle (55–60°C)SomeNone: Evidence A Replace carpets with hard flooringSomeNone: evidence A Acaricides and/or tannic acidWeakNone: Evidence A Minimize objects that accumulate dustNoneNone: Evidence B Use vacuum cleaners with integral HEPA filter and double- thickness bags WeakNone: Evidence B Remove, hot wash or freeze soft toysNoneNone: Evidence B PETS Remove cat/dog from the homeWeakNone: Evidence B Keep pet from main living areas/bedroomsWeakNone: Evidence B Use HEPA-filter air cleanersSomeNone: Evidence B Wash petWeakNone: Evidence B Replace carpets with hard flooringNoneNone: Evidence B Use vacuum cleaners with integral HEPA filter and double- thickness bags NoneNone: Evidence B SET OF ALLERGEN CONTROL MEASURES SomeSome: Evidence B Effectiveness of avoidance measures in rhinitis and asthma for certain indoor allergens

31. 31 © 2008 Universitair Ziekenhuis Gent Validation of guidelines Treat patients according to guidelines to usual practice Investigators randomised to: 225 patients with SAR 244 patients with SARscreened and enrolled Patients treated for 3 weeks Recorded: –Reflective symptoms twice daily –Medicine utilisation daily –RQLQ and SF-36 at day 7 and day 20 –Global evaluation at day 21 AB Bousquet J, van Cauwenberge P, Lund V Allergy 2003

32. 32 © 2008 Universitair Ziekenhuis Gent Benefits of a guided strategy Bousquet J, van Cauwenberge P, Lund V Allergy 2003

33. 33 © 2008 Universitair Ziekenhuis Gent Dissemination of ARIA guidelines Have you heard about ARIA?

34. 34 © 2008 Universitair Ziekenhuis Gent Implementation of ARIA guidelines Mild intermittent (n=69) Mild persistent (n=17) Mod/sev intermittent (n=445) Mod/sev persistent (n=273) Treated according to ARIA 56,5%64,7%45,4%63,0% Undertreated10,1%0%2,9%30,4% Overtreated33,3%35,3%51,7%6,6% Treatment prescribed by 95 Belgian GPs in 804 AR patients Van Hoecke H, Van Cauwenberge P, Allergy 2006

35. 35 © 2008 Universitair Ziekenhuis Gent Rhinitis treatment improves asthma EVIDENCE A ++Anti-IgE mAb Immunotherapy Leucotriene modifiers Nasal GCS +Antihistamines Revised GINA 2006: Rhinitis treatment

36. 36 © 2008 Universitair Ziekenhuis Gent Conclusion Aim of guidelines is to improve patient care and to support physicians by informing them and by improving their decisions Benefits of a guided strategy have been validated Several barriers to put guidelines into practice More efforts are needed to adapt guidelines to the needs of the end-users