Clinical Overview of Allergen Immunotherapy

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Clinical Overview of Allergen Immunotherapy Powered By Docstoc
					Rush and Cluster Immunotherapy

         Harold S. Nelson, MD
          Professor of Medicine
         National Jewish Health
  University of Colorado Health Science
                  Center
            Denver, Colorado
         Immunotherapy with a Standardized
       Dermatophagoides pteronyssinus Extract:
  III. Systemic reactions during the rush protocol in
            patients suffering from asthma.
      J Bousquet et al. J Allergy Clin Immunol 1989;83:797-802


 47/125 experienced systemic reactions:
 - Urticaria (4)
- Anaphylactic shock (8)
- Asthma exacerbations (35).
 Baseline FEV1 < 80% 73% systemic reactions.
Baseline FEV1 ≥ 80% 13% systemic reactions.
Difference all due to fewer asthma exacerbations.
         Immunotherapy with a Standardized
       Dermatophagoides pteronyssinus Extract:
        IV. Systemic reactions according to the
              immunotherapy schedule
         A Hajjaoui, et al. J Allergy Clin Immunol 1990;85:473-9


 To decrease systemic reactions serially introduced:
- Premedication: Oral CS, ketotiefen, Theophylline
(Group B)
- Premedication plus SIT givien only if FEV1 > 70%
and stopped for locals > 10 cm (Group C)
- Above plus RIT only four doses first day, then
single doses days 2, 5, 8, 11, & 14. (D)
 Systemic reactions according to the immunotherapy
                      schedule

                                                            Anaphyl
           Dose       SR’s       Urticaria     Asthma
                                                             axis

  RIT      2064       36%          12.7%         31%          5.1%

Pre-Med    1954       16%          3.8%          14%          1.8%

FEV1, lg
           1254       7.3%         0.6%           7%          0.2%
 locals

2-week     1662       5.4%         0.4%           5%          0.4%


            A Hajjaoui, et al. J Allergy Clin Immunol 1990;85:473-9
  Double-blind Comparative Study of
      Cluster and Conventional
    Immunotherapy Schedules with
   Dermatophagoides pteronyssinus.
     AI Tabar, et al. J Allergy Clin Immunol 2005;116:109-18

 239 patients with allergic rhinitis or asthma
  sensitive to house dust mites.
 Built up to a maintenance dose containing 3.2 g
  Der p 1 in an alum precipitated extract.
 Half by cluster with 15 shots in 6 weeks and half
  by 13 single weekly injections.
  Double-blind Comparative Study of
      Cluster and Conventional
    Immunotherapy Schedules with
   Dermatophagoides pteronyssinus.
Systemic reactions, all mild, occurred during the
 build-up stage in:

 Cluster: 3% of patients and 0.15% of injections.

 Weekly: 4% of patients and 0.31% of injections.



                  AI Tabar, et al. J Allergy Clin Immunol 2005;116:109-18
                              Decreased Prick Skin Tests

                    10
    Cut Tol Index




                                        *           *                                                     *
                                                                                                          *
                               *                     *
                                        *                                                     Cluster
                                                                                              Conventional

                     1
                         0    -    10                20            30          40                50           60
                         P0   P6    P12            P18         Weeks                                  P52

Cumlative Dose IT BU                                                        *Difference from P0; p<0.05
Cluster         25.3    25.3                41.3
Conventional         0.85           22.65          48.65
                                                           AI Tabar, et al. J Allergy Clin Immunol 2005;116:109
                                     Rhinitis Global Symptom-
                                         Medication Score
                                       1
Mean global score (standard error)

                                     0.9
                                     0.8                                                        Cluster

                                     0.7                                                        Conventional




                                                                     P=0.001
                                     0.6
                                     0.5
                                     0.4                                                    *             **
                                                                               *                          **
                                     0.3                                                    *
                                     0.2
                                     0.1
                                      0
                                                   T0                T1                   T1’         TF
                                           N       168               56                    55         143
                                               * Difference from T0 (wilcoxon, p<0.05)
                                               **Difference from T0 (wilcoxon, p<0.001)



                                                                 AI Tabar, et al. J Allergy Clin Immunol 2005;116:109
            Conclusions

 Build-up using alum-precipitated D.
pteronyssinus extract in a 6 week cluster
regimen was as well tolerated as a
conventional 12-week program of single
injections.
 Patients receiving cluster had more
rapid onset of immunologic response and
more rapid relief of symptoms.

               AI Tabar, et al. J Allergy Clin Immunol 2005;116:109
Experience at National
 Jewish with Cluster
Immunotherapy using
  Aqueous Extracts
         Cluster Immunotherapy
        Schedule: Injections B.I.W.
Visit          Vial            Dose
1              1:1000/1:100    0.1, 0.4 / 0.1
2              1:100/1:10      0.2, 0.4 / 0.07
3              1:10            0.1, 0.15, 0.25
4              1:10            0.35, 0.5
5              Full strength   0.07, 0.1
6              F.S.            0.15, 0.2
7              F.S.            0.3, 0.4
8              F.S.            0.5
   Cluster Immunotherapy: The
   National Jewish Experience
 3 dose-ranging studies, 2 with cat dander
extract and 1 with A-P dog extract.
 14 subjects received cluster to maintenance
dose of 15 g Fel d 1 and 7 to maintenance
dose of 15 g of Can d 1.
 1 mild systemic reaction (patient reached
projected maintenance with one extra
injection).
 Antihistamine pretreatment with cluster
immunotherapy: Premedication with loratadine
reduced the percent of patients with systemic
reactions from 79% to 33% (p = .002). Systemic
reactions were more severe in the placebo group.
Nielsen L, et al. JACI 1996;97:1207-13.
Administration of immunotherapy by a cluster
regimen:
- achieves both clinical and immunologic response
more rapidly
- does so with little or no increase in the risk of
systemic reactions.

				
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