1. Allergy Symptom Response Following Conversion from Injection Immunotherapy to Sublingual Immunotherapy CDR Timothy Clenney, MD, MPH Naval Medical Center Portsmouth Department of Otolaryngology/Head and Neck Surgery

2. Disclaimer Disclaimer The views expressed in this article are those of the author(s) and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. The views expressed in this article are those of the author(s) and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government..

3. Background Background Allergy immunotherapy has traditionally been administered via subcutaneous injection Allergy immunotherapy has traditionally been administered via subcutaneous injection Interest in non-injection routes, such as the sublingual route have arisen out of concerns for safety and convenience. Interest in non-injection routes, such as the sublingual route have arisen out of concerns for safety and convenience. Non-injection routes may be of particular interest for active duty personnel due to logistical and safety considerations of immunotherapy administration outside the MTF. Non-injection routes may be of particular interest for active duty personnel due to logistical and safety considerations of immunotherapy administration outside the MTF. Passalacqua, G., C. Lombardi, and G.W. Canonica, Curr Opin Allergy Clin Immunol 2004; 4(1)

4. Background Background Operational involvement in desert environments entails significant aeroallergen exposure Operational involvement in desert environments entails significant aeroallergen exposure Allergy control impacts asthma as well as allergic rhinitis (AR) Allergy control impacts asthma as well as allergic rhinitis (AR) During Initial Gulf war (1991), asthma was one of the most common causes of in-theater medical evacuation During Initial Gulf war (1991), asthma was one of the most common causes of in-theater medical evacuation Up to 78% of patients with asthma have AR and 38% of AR have asthma Up to 78% of patients with asthma have AR and 38% of AR have asthma Immunotherapy is often indicated when allergy and asthma cannot be controlled medically. Immunotherapy is often indicated when allergy and asthma cannot be controlled medically. Waibal KH. Allergic rhinitis in the Middel East. Military Medicine 2005 (170)

5. Background Background In Europe, sublingual immunotherapy (SLIT) has been regarded as a preferred alternative to subcutaneous immunotherapy since its introduction in 1986. In Europe, sublingual immunotherapy (SLIT) has been regarded as a preferred alternative to subcutaneous immunotherapy since its introduction in 1986. In the United States, sublingual route is not FDA approved and is an “off-label” use. In the United States, sublingual route is not FDA approved and is an “off-label” use. Although the efficacy and safety of SLIT are well established, no studies have examined symptom control in patients converted from injection immunotherapy to SLIT Although the efficacy and safety of SLIT are well established, no studies have examined symptom control in patients converted from injection immunotherapy to SLIT Leatherman BD, et al. Otolaryngol Head Neck Surg 2007;136

6. AIMS AIMS Determine the allergy symptom response in patients converted from injection immunotherapy to SLIT Determine the allergy symptom response in patients converted from injection immunotherapy to SLIT Assess allergy-related quality of life in a cohort of patients converted from injection immunotherapy to SLIT Assess allergy-related quality of life in a cohort of patients converted from injection immunotherapy to SLIT Examine the effectiveness and utility of SLIT in a small group of active-duty military personnel Examine the effectiveness and utility of SLIT in a small group of active-duty military personnel

7. Methods Methods Questionnaires were offered to a sample ENT allergy patients receiving SLIT that had previously been managed with injection immunotherapy Questionnaires were offered to a sample ENT allergy patients receiving SLIT that had previously been managed with injection immunotherapy –Four categories of allergy symptoms: Eye Symptoms Eye Symptoms Nasal Symptoms Nasal Symptoms Sleep Symptoms Sleep Symptoms Constitutional symptoms Constitutional symptoms –Quality of life was assessed using a validated rhinoconjunctivitis QOL instrument Juniper EF, Thompson AK, Ferrie PJ, et al. Clinical and experimental allergy 2000; 30 (1)

8. All patients continued current allergy medical treatments (antihistamines,etc) All patients continued current allergy medical treatments (antihistamines,etc) Multi-antigen SLIT was started on all patients using a standardized protocol ⁴ Multi-antigen SLIT was started on all patients using a standardized protocol ⁴ Antigen treatment concentration was based upon the results of allergy in-vitro testing Antigen treatment concentration was based upon the results of allergy in-vitro testing This study was approved by the Naval Medical Center Portsmouth institutional review board This study was approved by the Naval Medical Center Portsmouth institutional review board Methods

9. 200 patients currently receiving SLIT 200 patients currently receiving SLIT 58 of the 200 had previously received injection immunotherapy 58 of the 200 had previously received injection immunotherapy –28 patients lost to follow-up or not available during the study period –30 patients receiving SLIT were invited to participate in this survey –100% agreed to participate Results

10. Subject Characteristics % Male 51.7% Average age (years) 48.6 SD 15.1 % Active Duty Military 27.5% Type of Allergy Seasonal 10 (34%) Perennial 20 (66%)

11. Immunotherapy History Duration (months) Range (months) Std Dev Average time on injection immunotherapy 37.61 - 18245.4 Average time on SLIT 14.82 - 24 6.5 Average time between injection immunotherapy and SLIT 1.21 - 10 2.06

12. Concurrent Medical Therapy with SLIT Concurrent Medical Therapy with SLIT

13. Results Nasal Symptoms –30 (100%) reported nasal symptoms. 22(73%) – Improved nasal symptoms 22(73%) – Improved nasal symptoms 8 (28%) – No change in nasal symptoms 8 (28%) – No change in nasal symptoms 0 (0%) – Worsening of nasal symptoms 0 (0%) – Worsening of nasal symptoms P = 0.016 P = 0.016

14. Results Results Eye Symptoms –27 (90%) reported eye symptoms 19 (70%) – Improved eye symptoms 19 (70%) – Improved eye symptoms 7 (26.9%) – No change in eye symptoms 7 (26.9%) – No change in eye symptoms 1 (3%) – Worsening of eye symptoms 1 (3%) – Worsening of eye symptoms P < 0.001 P < 0.001

15. Results Results Sleep Symptoms –26 (86%) reported sleep symptoms 12 (46%) – Improved sleep symptoms 12 (46%) – Improved sleep symptoms 13 (50%) – No change in sleep symptoms 13 (50%) – No change in sleep symptoms 1 (3%) – Worsening in sleep symptoms 1 (3%) – Worsening in sleep symptoms P=0.006 P=0.006

16. Constitutional Symptoms –26 (86%) reported constitutional symptoms 15 (58%) – Improved constitutional symptoms 15 (58%) – Improved constitutional symptoms 9 (35%) – No change in constitutional symptoms 9 (35%) – No change in constitutional symptoms 2 (7%) – Worsening of constitutional symptoms 2 (7%) – Worsening of constitutional symptoms P = 0.008 P = 0.008 Results Results

17. Symptom Control Following Conversion to SLIT Constitutional P = 0.016 P<0.001 P=0.006 P=0.008

18. Mean Rhinoconjunctivitis QOL score (0 – 84) Std Dev Subjects converted from SCIT to SLIT (N = 30) 19.212.4 Rhinoconjunctivitis QOL

19. SLIT in Active-Duty Military 15 active-duty patients receiving SLIT 15 active-duty patients receiving SLIT –8 previously on injection IT –7 No previous immunotherapy No reported adverse reactions No reported adverse reactions None discontinued therapy None discontinued therapy 3 deployed while receiving SLIT 3 deployed while receiving SLIT

20. Rhinoconjunctivitis QOL (military group) Mean Rhinoconjunctivitis QOL score (0 – 84) Std Dev Subjects converted from SCIT to SLIT (N = 30) 14.17.4

21. Concurrent Medical Therapy Concurrent Medical Therapy (military group) (military group)

22. Discussion The primary objective of this study was to determine the self-reported clinical response to sublingual immunotherapy (SLIT) among patients previously managed with subcutaneous injected immunotherapy (SCIT). The primary objective of this study was to determine the self-reported clinical response to sublingual immunotherapy (SLIT) among patients previously managed with subcutaneous injected immunotherapy (SCIT). The results of this study, though limited by small sample size, suggest that most patients can be converted from injection immunotherapy to sublingual immunotherapy with good symptom control. The results of this study, though limited by small sample size, suggest that most patients can be converted from injection immunotherapy to sublingual immunotherapy with good symptom control.

23. Discussion Specific symptom control reported by patients were consistent with rhinoconjuctivitis quality of life scores which suggested overall good quality of life based on a validated instrument. Specific symptom control reported by patients were consistent with rhinoconjuctivitis quality of life scores which suggested overall good quality of life based on a validated instrument. These results are tempered by the fact that most patients continued to use allergy pharmocotherapy to manage symptoms. These results are tempered by the fact that most patients continued to use allergy pharmocotherapy to manage symptoms. Because military personnel are often unable to use injection immunotherapy due to logistical limitations, we evaluated the use SLIT in this group. Because military personnel are often unable to use injection immunotherapy due to logistical limitations, we evaluated the use SLIT in this group.

24. Discussion In this smaller, separate analysis, military personnel using SLIT reported very good rhinoconjunctivitis quality of life scores, whether or not they previously received immunotherapy. In this smaller, separate analysis, military personnel using SLIT reported very good rhinoconjunctivitis quality of life scores, whether or not they previously received immunotherapy. Concurrent pharmacotherapy was used less often by military personnel Concurrent pharmacotherapy was used less often by military personnel The potential benefit here may be limiting medication side-effects The potential benefit here may be limiting medication side-effects

25. Conclusions Allergy patients receiving injection immunotherapy can be converted to SLIT with either improvement or no reduction in rhinoconjunctivitis symptom control. Allergy patients receiving injection immunotherapy can be converted to SLIT with either improvement or no reduction in rhinoconjunctivitis symptom control. Patients converted from injection immunotherapy to SLIT report good overall quality of life Patients converted from injection immunotherapy to SLIT report good overall quality of life Because it can be safely self-administered and efficacious, SLIT may be an ideal approach to allergy management when immunotherapy is indicated for military personnel. Because it can be safely self-administered and efficacious, SLIT may be an ideal approach to allergy management when immunotherapy is indicated for military personnel.

26. References 1) Passalacqua, G., C. Lombardi, and G.W. Canonica, Sublingual immunotherapy: an update. Curr Opin Allergy Clin Immunol 2004; 4(1) 2) Leatherman BD, Owen S, Parker M, et al. Sublingual immunotherapy: Past, present, paradigm for the future? A review of the literature. Otolaryngol Head Neck Surg 2007;136 3) Juniper EF, Thompson AK, Ferrie PJ, et al. Development and validation of the Mini Rhinoconjunctivitis Quality of Life Questionnaire. Clinical and experimental allergy 2000; 30 (1) 4) La Crosse Method, sublingual immunotherapy practice protocol, 2008. Allergychoices, inc La Crosse Wi.