subject: introdução à medicina long-term preventive effects of allergen specific immunotherapy: a...

Subject: Introdução à Medicina

Long-term preventive effects of allergen specific

immunotherapy: a systematic review and

meta-analysis


Regente da disciplina: Prof Dr. Altamiro da Costa

Orientador: Dr. João Fonseca

Azevedo L; Cardoso P; Coelho J; Gonçalves A; Maranhas M; Oliveira A;

Pereira E; Pereira J; Silva V; Teixeira C; [email protected]


SUMMARY•Introduction

•Objectives

•Participants and methods

> Criteria Selection

> Search Strategy

•Results

> Identification and selection of the literature

> Description of the included articles

> Methodological quality assessment

> Data extraction and analysis

•Preliminary Discussion

•References


INTRODUCTION

• “Allergic diseases and asthma “have increased dramatically during the past 2 decades”2

• Today these diseases are very frequent; 2.7 million children in the United States suffer from asthma and over a hundred million people suffer from asthma, allergy and

chronic obstructive pulmonary disease in Europe.3

2. TePas EC, Umetsu DT. Immunotherapy of asthma and allergic diseases. California (USA): Department of Pediatrics, Stanford University; 2000 Dec; 12(6):574-8.

3. Chin ES. Pediatrics, Reactive Airway Disease. Slapper D, Windle ML, Young GM, Halamka J, Bachur RG, editors. EMedicine from WebMD. 2006 Nov.


There is a chance that immunotherapy can prevent the evolution from rhinitis to asthma and the appearance of new sensitivities

•There is no systematic review proving its long-

term efficacy on the prevention of new sensitivities

and the evolution from rhinitis to asthma.

HOWEVER…


SIT group

Control group

Progression from rhinitis to asthma?

New allergic sensitivities?

End ofthe

intervention

During the study Follow -up

Patients with allergic diseases

- Decrease symptoms;- Decrease medication.

End ofFollow-up

Figure 1 – Graphic contextualising the problem of this systematic review.


OBJECTIVES

Search if allergen specific immunotherapy has long-term

preventive effects after the treatment ceases

Development of new sensitivities The evolution from rhinitis to asthma

This has motivated us to make a systematic review, to investigate the veracity

of this hypothesis


To search PUBMED DATABASE

•Query:("Immunotherapy"[MeSH Terms] OR "Immunotherapy"[All Fields] OR ("desensitization, immunologic"[MeSH Terms] OR "desensitization"[All Fields]) AND (("asthma"[MeSH Terms] OR "asthm*"[All Fields]) AND ("rhinitis"[MeSH Terms] AND "rhinitis"[All Fields]) OR ("airway diseases"[All Fields])) AND sensitive clinical query from PUBMED

Search strategy


Search strategy

• We also searched the references of the included studies and

consult the review articles that already exist about the subject. 7, 9,13

Furthermore …

7. Cox L, Cohn JR. Duration of allergen immunotherapy in respiratory allergy: when is enough, enough?. Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma & Immunology. 2007 May; 98(5):416-26.

9. Passalacqua G, Durham SR. Allergic rhinitis and its impact on asthma update: allergen immunotherapy. The Journal of Allergy and Clinical Immnunoly. 2007 Apr;119(4):881-91.

13. Calamita Z, Saconato H, Pela AB, Atallah AN. Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method. Allergy. 2006 Oct;61(10):1162-72.


PARTICIPANTS AND METHODS

Article criteria selection

Inclusion criteria Exclusion criteria


Inclusion criteria

• Articles which refer to patients with allergic rhinitis or asthma treated with SIT; • Studies with, at least, one year of follow-up after the treatment ceases;

• Articles reporting original data on the effects of immunotherapy on the: - progression from rhinitis to asthma ;- appearance of new allergic sensitivities;

• Controlled studies.


Exclusion criteria

• Studies without a rigorous definition about the existence or not of asthma in the patients, at the beginning of the treatment;

• Studies that combine SIT with other types of treatment or medication;

• Studies in other language than the English.


RESULTS


Identification and selection of the literature

10 reports excluded- 9 without one year, at least, of follow-up- 1 not relative to patients suffering from asthma and/or rhinitis

14 electronically screened for detailed

evaluation

392 excluded based on title/abstract

125 excluded - review articles

531 references identified electronically

4 reports included 3 articles included after consulting the references of review papers on this subject

7 studies included on the systematic review


The articles were analyzed according to:

• Study identification: author, year, country

• Type of study;

• Study’s objective;

• Participants: number, age (children or adults), sex, health condition

• Interventions: use of SLIT or SCIT, type of allergen administrated

• Variables analysed: progression from rhinitis to asthma in patients treated

with SIT and in group control, severity of the symptoms (if developed),

development of new sensitivities in both patient groups, type of sensitivity

developed (if developed), behaviour’s differences in both groups;

Description of the included articles


• Type of treatment;

• Treatment duration;

• Follow-up duration;

• Control or placebo group;

• Time: seasonal, not-seasonal, co-seasonal;

• Results: development or not of asthma’s symptoms in patients with

rhinitis that didn’t have asthma at the beginning of the study; appearance

or not of new allergic sensitivities; development of other kinds of

symptoms.


The participants of the included studies weren’t completely equals

4 studies > participants were children

3 Studies > participants were adults


In two of them (L. Jacobsen et al. and B. Niggmenn, et al.)

Participants at the beginning suffered from rhinoconjunctivitis

In other four

Participants initially had rhinitis and/or asthma

Eng PA, et al 2002 study

Participants suffered from a sensitivity to grass pollen with or without tree pollen


Type of treatment administrated:

L. Jacobsen et al. and B. Niggmenn,

et al.

Di Rienzo V, et al Three studies

P. A. Enget al. 2002

SCIT:- Phleum pratense and Betula verrucosa

SLIT SCIT : - grass pollen allergen extracts

Didn’t specify the type of

SIT administrated.


Period of treatment duration:

3 - 5 years

Period of follow – up:

It ranged from 3 to 12 years


Methodological quality assessment

Delphi list

D1 Was a method of randomization performed?

D2 Was the treatment allocation concealed?

D3 Were the groups similar at baseline regarding the most important prognostic indicators?

D4 Were both inclusion and exclusion criteria specified?

D5 Was the outcome assessor blinded?

D6 Was the care provider blinded?

D7 Was the patient blinded?

D8 Were point estimates and measures of variability presented for the primary outcome measures?

D9 Did the analysis include an intention-to-treat analysis?

D10 Was the withdrawal/drop-out rate <20% of the total study population?

D11 Was the withdrawal/drop-out rate unlikely to cause bias?

Table 1 – Items of the Delphi-list for the assessment of the methodological quality of the articles.


Methodological quality assessment

Article D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 Total Delphi*L. Jacobsen, et al.2007 1 0 1 0 1 0 0 1 1 0 0 5

B. Niggemann, et al.2006 1 0 1 0 1 0 0 1 1 0 0 5Pajno GB, et al.2001 0 0 1 1 0 0 0 1 1 1 1 6Di Rienzo V, et al.2003 0 0 1 0 0 0 0 1 1 1 1 5Eng, PA, et al. 2006 0 0 1 0 0 0 0 1 1 1 1 5Eng, PA, et al. 2002 0 0 1 0 0 0 0 1 1 1 1 5Durham SR., et al.1999 0 0 1 1 0 0 0 1 1 0 0 4

* Total Delphi (range 0-11): total score >/= 6 = high quality; <6 = low quality

* Total Delphi (range 0-11): total score >/= 6 = high quality; <6 = low quality

Table 2 - Results of the methodological quality assessment.


Data extraction and analysis

DEVELOPMENT OF NEW SENSITIVITIES



Pajno GB, et al. 2002

• 75.4% of the children in SIT group didn’t show any sensitization • 33.3% in control group• (p < 0.0002)

Eng PA, et al. 2002

• 61% (8 out of 13) of the SIT patients developed a new sensitivity• 100% (10 out of 10) in control group

Eng PA, et al. 2006• the prevalence of sensitizations was: - 90% in the control group

- 67% in the SIT group

In comparison to a previous observation that has been made six years before none of the patients (control or SIT group) have developed new sensitizations in this period



Stephen R. Durham, et al.

• decrease of late skin response to an allergen after the discontinuation of SIT >> No numbers or percentages



0%0%Eng PA, et al. 2006

100%61%Eng PA, et al. 2002

67%25%Pajno GB, et al. 2002

Control GroupSIT GroupStudy

Table 3 - Results obtained by the included studies on the development of new sensitivities.



Figure 2 - Graphic of the results obtained by the included studies on the development of new sensitivities.



DEVELOPMENT OF ASTHMA SYMPTONS



Di Rienzo V, et al.

• 91% of the patients of SLIT group didn’t develop asthma• 4% in the control group• Increase of the number of patients with multiple sensitizations in SLIT group, in comparison with the control group.

L. Jacobsen, et al.

• 25% (16 out of 64) patients in SIT group developed asthma symptons• 45% (24 out of 53) in control group

B. Niggemann, et al.

• 20% (15 out of 75) of the patients in SIT group evoluted from rhinitis to asthma• 43% (29 out of 87) in control group



Table 4 - Results obtained by the included studies on the progression from rhinitis to asthma.

43%20%B. Niggemann, et al. 2006

45%25%L. Jacobsen, et al. 200796%9%Di Rienzo V, et al. 2003

Control GroupSIT GroupStudy



Figure 3 - Graphic of the results obtained by the included studies on the progression from rhinitis to asthma.



DEVELOPMENT OF ASTHMA SYMPTONSDEVELOPMENT OF NEW SENSITIVITIES

2 trials: SIT is preventive

3 trials: SIT is preventive


META – ANALYSIS:

Figure 4 - Meta-analysis of development of asthma symptoms (all included studies on this subject): odds ratio (OR) with 95% confidence interval (CI) for each study and all studies combined (include test for heterogeneity).


META – ANALYSIS:

Figure 5 - Meta-analysis of development of asthma symptoms: odds ratio (OR) with 95% confidence interval (CI) for each study and all studies combined (include test for heterogeneity).


META – ANALYSIS:

Figure 6 - Meta-analysis of development of new sensitivities: odds ratio (OR) with 95% confidence interval (CI) for each study and all studies combined (include test for heterogeneity).


Allergen specific immunotherapy

reduces

Symptoms of allergies

Stop the progression from

rhinitis to asthma

Decrease the development of

new sensitivities long after the

treatment finished

PRELIMINARY DISCUSSION


REFERENCES

1. Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database of Systematic Reviews. 2003; (4):CD001186. 2. TePas EC, Umetsu DT. Immunotherapy of asthma and allergic diseases. Current Opinion in Pediatrics. 2000 Dec; 12(6):574-8. 3. Chin ES. Pediatrics, Reactive Airway Disease. Slapper D, Windle ML, Young GM, Halamka J, Bachur RG, editors. EMedicine from WebMD. 2006 Nov. 4. James T. Li, MD, PhD; Richard F. Lockey, MD; I. Leonard Bernstein, MD;Jay M. Portnoy, MD; and Richard A. Nicklas, MD, editors. Allergen immunotherapy: a practice parameter. The Journal of allergy and clinical immunology. 2003 Jan; 90(1):13-4.

5. O’Hehir RE, Sandrini A, Anderson GP, Rolland MJ. Sublingual allergen immunotherapy:immunological mechanisms and prospects for refined vaccine preparation. Current Medicinal Chemistry. 2007;14(21):2235-44. 6. Greenberger PA, Ballow M, Casale TB, Platts-Mills TA, Sampson HA. Sublingual immunotherapy and subcutaneous immunotherapy: Issues in the United States. The Journal of Allergy and Clinical Immnunoly. 2007 Oct 12; In Press, Corrected Proof.


REFERENCES

7. Cox L, Cohn JR. Duration of allergen immunotherapy in respiratory allergy: when is enough, enough?. Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma & Immunology. 2007 May; 98(5):416-26. 8. Malling HJ. Allergen-specific immune therapy in the treatment of asthma. Ugeskrift for Laeger. 2000 Jan 24; 162(4):477-9. 9. Passalacqua G, Durham SR. Allergic rhinitis and its impact on asthma update: allergen immunotherapy. The Journal of Allergy and Clinical Immnunoly. 2007 Apr;119(4):881-91. 10. Jacobsen L, Nuchel Petersen B, Wihl JAÊ , et al. Immunotherapy with partially purified and standardized tree pollen extracts. IV: Results from long-term (6-year) follow-up. Allergy. 1997; 52:914±920. 11. Johnstone DE, Dutton A. The value of hyposensitization therapy for bronchial asthma in children: a 14-year study. Pediatrics. 1968; 42:793±802.


REFERENCES

12. Des Roches A, Paradis L, Menardo JL, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI: Specific immunotherapy prevents the onset of new sensitizations in children. The Journal of Allergy and Clinical Immnunoly. 1997; 99:450±453. 13. Calamita Z, Saconato H, Pela AB, Atallah AN. Efficacy of sublingualimmunotherapy in asthma: systematic review of randomized-clinical trialsusing the Cochrane Collaboration method. Allergy. 2006 Oct;61(10):1162-72.

subject: introdução à medicina long-term preventive effects of allergen specific immunotherapy: a...

Documents

immunotherapy of asthma

asthma immunology

introduo medicina regente

asthma update

allergic rhinitis

hypothesis slide

pubmed search strategy

systematic review