Is Montelukast efficacious in reducing the symptoms of rhinitis in adult

patients?

13-07-2006 1Introdução à Medicina II

Table of contents

03-06-2011 Introdução à Medicina II 2

• Introduction• Methods• Results• References

Table of contents

Introdução à Medicina II 3

• Introduction– Background– Research Question– Aims

• Methods • Results• References

03-06-2011

Introduction Research Question Methods Results DiscussionAims

Backgroud- Rhinitis

• Inflammation of the nasal mucosa, the mucous membrane lining the nasal cavities.

4Introdução à Medicina II

[1]

[1] M Ciebiada, Quality of Life in Patients With Persistent Allergic Rhinitis Treated With Montelukast Alone or in Combination With Levocetirizine or Desloratadine, Medical University of Lodz, Department of Pneumology and Allergy, Lodz, Poland

03-06-2011

Introduction Research Question Methods Results DiscussionAims

Backgroud - Rhinitis versus Asthma

• Rhinitis and asthma are linked by common epidemiological, clinical and inflammatory features[2]

5Introdução à Medicina II

[2] Castillo JA, Navarro A, Quirce S, Molina J, García-Marcos L, Juliá B, Valero A, Mullol J. Prevalence and characteristics of rhinitis in adult asthmatic patients attending allergist, primary care and pulmonologist settings in Spain.

03-06-2011

Introduction Research Question Methods Results DiscussionAims

Background - Montelukast

•Montelukast is a systemically active drug with a targeted, dual mechanism of action, acting both as a bronchodilator and anti-inflammatory[3]

•Montelukast is an anti-inflammatory agent that was initially developed as a therapy for asthma and is now increasingly being applied to the treatment of seasonal and perennial allergic rhinitis[4]

6Introdução à Medicina II

[4] Day JH, Briscoe MP, Ratz JD, Efficacy of levocetirizine compared with montelukast in subjects with ragweed-induced seasonal allergic rhinitis in the Environmental Exposure

[3] Diamant Z, Mantzouranis E, Bjermer L. Montelukast in the treatment of asthma and beyond. Department of Allergology.

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Introduction Research Question Methods Results DiscussionAims

Hypothesis and Research Question

10Introdução à Medicina II

Montelukast

Used in asthma treatment

The treatments of rhinitis and asthma are usually overlapping

We want to study

Is Montelukast efficacious in

reducing the symptoms of

rhinitis in adult patients compared to placebo and

other treatments?

03-06-2011

Introduction Research Question Methods Results DiscussionAims

Aims

• Evaluate the efficacy of Montelukast in reducing symptoms among adults who suffer from rhinitis.

• Compare the efficacy of Montelukast in the treatment of rhinitis with the results obtained using conventional anti-rhinitis medication.

• Compare the efficacy of Montelukast with the placebo effect

• Assess if the simultaneous presence of asthma and rhinitis in a Montelukast treated patient may bring any impact in the drug’s efficacy.

11Introdução à Medicina II03-06-2011

Table of contents

Introdução à Medicina II 9

• Introduction• Methods - Flowchart - Systematic review - Study design - Data colection methods - Queries - Articles selection - Variables description

• Results

• References

03-06-2011

Introdução à Medicina I

Methods and Participants

Flowchart

03-06-2011

Introduction Research Question Methods Results DiscussionAims

Systematic Review

• A systematic review is a critical assessment and evaluation of all research studies that address a particular clinical issue.

• Selection, evaluation, presentation, analysis and synthesis of evidence.

• Aggregation of appropriate and representative results, to achieve an adequate answer.

11Introdução à Medicina II03-06-2011

Introduction Research Question Methods Results DiscussionAims

Introdução à Medicina I

Population

Intervention

Outcome

Adults with Rhinitis

Adults with concomitant asthma and rhinitis

Montelukast

Rhinitis’s conventional medication

Placebo

Reducing symptoms

Study Design

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Introduction Research Question Methods Results DiscussionAims

Data Collection Methods

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Systematic review using:

ISI Web of Knowledge

SCOPUSPubMed

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Introduction Research Question Methods Results DiscussionAims

Queries

((clinical[Title/Abstract] AND trial[Title/Abstract]) OR clinical trials[MeSH Terms] OR clinical trial

Intervention

Disease

Population

Clinical query

(“montelukast “[all fields] OR “Leukotriene Antagonists “[Pharmacological Action])

((Adults [Mesh]) OR (Adults [all fields]))

OR (“Rhinitis, Allergic, Seasonal”[Mesh]) OR (“Rhinitis, Allergic, Perennial”[Mesh]))

((clinical[Title/Abstract] AND trial[Title/Abstract])

[Publication Type] OR random*[Title/Abstract] OR random allocation[MeSH Terms] OR

therapeutic use[MeSH Subheading])

AND

AND

AND

((“Rhinitis”[tiab])

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Introduction Research Question Methods Results DiscussionAims

Queries

20Introdução à Medicina I

Rhinitis AND Montelukast AND Adults

Key-word

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Introduction Research Question Methods Results DiscussionAims

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SCOPUS(104/198)

ISI WEB(17/43)

PUBMED(150/150)

271 First Selection - Title - Abstract

88Second Selection - Full article

56 14After searching full

text

To be excluded, both reviewers have to disapprove

5 groups 5 groups

Articles Selection

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Introduction Research Question Methods Results DiscussionAims

Introdução à Medicina I

SCOPUS(104/198)

ISI WEB(17/43)

PUBMED(150/150)

271 First Selection - Title - Abstract

88Second Selection - Full article

56 14After searching full

text

To be excluded, both reviewers have to disapprove

5 groups 5 groups

Articles Selection

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Introduction Research Question Methods Results DiscussionAims

Inclusion and exclusion criteria

• Adults participants (>15y)• The articles must mention the medication

Montelukast• The articles must be related with rhinitis• The articles have to compare the treatment

with Montelukast and other drugs or placebos

Inclusion Criteria

Exclusion Criteria

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•Articles over 20 years old•Articles not written in Portuguese,

Spanish or English•Sistematic review articles•Study length shorter than two

weeks

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Introduction Research Question Methods Results DiscussionAims

Form – First Selection

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Introduction Research Question Methods Results DiscussionAims

First Selection Results

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32%68%

ApprovedDisapproved

Articles Selection

73%

27% Both approvedOnly one approved

Articles Selection

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Introduction Research Question Methods Results DiscussionAims

Exclusion Reasons – First Selection

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5%1%

22%

6%

28%

18%

9%

11%

Article is not written in portuguese, english or spanish.

Article is not understandable/logical.

Article does not refer Montelukast.

Participants have less than 15 years old.

Article is not related with rhinitis.

Article does not compare Montelukast with othe drugs.

Article has no abstract.

Article is a systematic review.

Exclusion Reasons

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Introduction Research Question Methods Results DiscussionAims

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Form – Second Selection

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Introduction Research Question Methods Results DiscussionAims

Exclusion Reasons – Second Selection

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23%

16%

31%

4%

2%

18%

6%

Article is not related with rhinitis.

Article does not refer Montelukast.

Article does not compare Montelukast with other drugs.

Article is not understandable.

Age of participants lower than 15 years old.

Article tests Montelukast combined with other drugs.

Study lenght lower than two weeks.

Exclusion reasons

03-06-2011

Introduction Research Question Methods Results DiscussionAims

Our Articles

Introdução à Medicina I

NUMBER CODE TITLE

11 Rohit K., 2010 Adding montelukast to fluticasone propionate/salmeterol forcontrol of asthma and seasonal allergic rhinitis

19 Susan Lu, 2009 Clinical Studies of Combination Montelukast and Loratadine in Patientswith Seasonal Allergic Rhinitis

40 M Ciebiada, 2008 Quality of Life in Patients With Persistent Allergic Rhinitis Treated With Montelukast Alone or in Combination With Levocetirizine or Desloratadine

41 Kimihiro Okubo, 2008

A Double-Blind Non-inferiority Clinical Study of Montelukast, a Cysteinyl Leukotriene Receptor 1 Antagonist, Compared with Pranlukast in Patientswith Seasonal Allergic Rhinitis.

43 Kimihiro Okubo, 2008

Therapeutic Effect of Montelukast, a Cysteinyl Leukotriene Receptor 1Antagonist, on Japanese Patients with Seasonal Allergic Rhinitis

47 Carah B. Santos, 2008

The role of montelukast on perennial allergic rhinitis and associated sleep disturbances and daytime somnolence

57 George Philip,2007

Efficacy of montelukast for treating perennial allergic rhinitis

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Introduction Research Question Methods Results DiscussionAims

Introdução à Medicina I

NUMBER CODE TITLE

72 J.Chr. Virchowa, 2006

Efficacy and safety of montelukast in adults with asthma and allergic rhinitis

76 Eli O. Meltzer,2005

Montelukast Effectively Treats the Nighttime Impact of Seasonal Allergic Rhinitis

110 J. Van Adelsberg1, 2003

Montelukast improves symptoms of seasonal allergic rhinitis over a 4-week treatment period

139 A.M . Wilson, 2001 A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma

143 Eli O. Meltzer, 2000 Concomitant montelukast and Ioratadine as treatment for seasonal allergic rhinitis

177 Munawar Alam Ansari,

Montelukast versus nigella sativa for management of seasonal allergic rhinitis: a single blind comparative clinical trial

250 Carlos E. Baena-Cagnani, 2003

Comparative Effects of Desloratadine versus Montelukast on Asthma Symptoms and Use of ß2-Agonists in Patients with Seasonal Allergic Rhinitis and Asthma

Our Articles

03-06-2011

Introduction Research Question Methods Results DiscussionAims

Variables Description

21Introdução à Medicina II

Bibliographic Research

•Authors•Country of publishing•Year of publishing

Methods used in the

article

•Study design•Length•Type of sampling•Recruitment characteristics•Dropouts•Intervention concealment

Analysis of the articles

•Number of participants•Summary measures- mean, mode, median

•Measures of variability of the difference between Montellukast and its comparators- standard deviation

Variables Description

03-06-2011

Introduction Research Question Methods Results DiscussionAims

Variables to Be Extracted

Treated pathology and other diseases

; Number of study participants, grouped by sex

Participants’ characteristics (mean age, gender, etc.)

Type of medication taken during the study

Unit of measurement and methods of administration

Sample

Introdução à Medicina I03-06-2011

Introduction Research Question Methods Results DiscussionAims

Variables to Be Extracted

Weight and height of participants and the used measure unit Participants selection method

: Type of study and study length

Dropouts Results after treatement (side effects and symptoms)

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Introduction Research Question Methods Results DiscussionAims

Comparisons

Introdução à Medicina I

Comparison between the following groups:

Monteluklast

Placebo

Montelukast

Other Medication

Montelukast

Placebo

Montelukast

Other medicationMontelukast

Adults + RhinitisWithout

treatment

Adults + Rhinitis + Asthma

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Introduction Research Question Methods Results DiscussionAims

Statistical Analysis

Introdução à Medicina I

Meta- Analysis

• Meta-analysis is a quantitative synthesis of evidence, using appropriate statistical methodology.

Analysis

Quantitative

Qualitative

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Introduction Research Question Methods Results DiscussionAims

Gantt Map

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Gantt Map

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Table of contents

Introdução à Medicina II 32

• Introduction• Methods • Results - Database - Metanalysis

• Discussion • References

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Introduction Research Question Methods Results DiscussionAims

Database

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Database

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Introduction Research Question Methods Results DiscussionAims

Results: A systematic review and Metanalysis

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Meta- Analysis

Analysis

Quantitative

Qualitative

In the last presentation …

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Introduction Research Question Methods Results DiscussionAims

Results: A systematic review and Metanalysis

Introdução à Medicina I

Meta- Analysis

Analysis

Quantitative

Qualitative

Now …

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Introduction Research Question Methods Results DiscussionAims

Daytime score

Montelukast vs. Placebo

Nighttime score

Composite score

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Introduction Research Question Methods Results DiscussionAims

Daytime score

Montelukast vs. Antihistamine

Composite score

Nightime score

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Introduction Research Question Methods Results DiscussionAims

Statistical Values

Introdução à Medicina I

Heterogeneity (I2) values were higher than 90% in most cases (only nighttime symptoms with montelukast vs. antihistamine was very low)

None of the results was found to be statistically significant, with the lowest value of p being p=0.07 (we considered p<0.05 for significance)

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Introduction Research Question Methods Results DiscussionAims

Qualitative Analysis

• Montelukast is significatively more eficacious than the corticosteroids in study (Baba 2008).

• Relatively to N. Sativa, montelukast is more efficacious (p<0.001) in the daytime score symptoms after 14 days (Ansari 2010).

• In comparison with placebo and antihistamine, we cannot reach a definitive conclusion, but we detected a tendency to montelukast be more efficacious.

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Table of contents

Introdução à Medicina II 40

• Introduction• Methods• Results• Discussion - Limitations - Future perspectives • References

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Introduction Research Question Methods Results DiscussionAims

Discussion

• Number of participants (between 20-521 in each group);

• Study lenght (between 3 weeks and 6 months);

• Number of total dropouts (between 2-79).

The type of study and the secondary effects could also be a heterogeneity factor, but we verified that there are many missing values for secondary effects and the types

of study aren’t actually very variable.

Heterogeneity

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Introduction Research Question Methods Results DiscussionAims

Discussion

Study Characteristics

Introduction Research Question Methods Results DiscussionAims

Conclusion

3-6-2011 Introdução à Medicina I

Meta-analysis performed found no differences between the efficacy of montelukast and

conventional medication’s (antihistamines) or placebo’s. However, qualitative analysis suggests there might be a tendency towards montelukast

showing better results than its terms of comparison, but in a subtle, unconvincing way.

Introduction Research Question Methods Results DiscussionAims

Discussion

Positive points

Introdução à Medicina II

• We sent e-mails to the authors to obtain the maximum number of full text articles

• The articles were reviewed by different researchers

and were divided in a random way

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Introduction Research Question Methods Results DiscussionAims

Limitations

• Some articles did not have symptom scores evaluation as primary outcome

• There is a big diversity of rhinitis treatments, which leads to the presence of many terms of comparison for Montelukast

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Introduction Research Question Methods Results DiscussionAims

Limitations

Introdução à Medicina I

•The efficacy of rhinitis treatments can be controversial

•We had to deal with different perspectives during the articles selection

•Some of the articles do not have full texts available

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Introduction Research Question Methods Results DiscussionAims

But…

Can our project output begeneralized or transferred?

Adults ≠ Children Elder People≠POPULATION

Adults Z

Children Elder People03-06-2011

Introduction Research Question Methods Results DiscussionAims

Future Perspectives

Introdução à Medicina I

• More homogeneity/accordance in values presentation

• More articles about rhinitis

• New meta-analysis

• Studies in other age groups

03-06-2011

SITE

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Table of contents

Introdução à Medicina II 50

• Introduction• Methods• Results• Discussion• References

03-06-2011

Introduction Research Question Methods Results DiscussionAims

References

• Lagos JA, Marshall GD. Montelukast in the management of allergic rhinitis. Division of Clinical Immunology and Allergy, University of Mississippi Medical Center Jackson, MS, USA. Ther Clin Risk Manag. 2007 Jun;3(2):327-32.

• Castillo JA, Navarro A, Quirce S, Molina J, García-Marcos L, Juliá B, Valero A, Mullol J. Prevalence and characteristics of rhinitis in adult asthmatic patients attending allergist, primary care and pulmonologist settings in Spain. Servei de Pneumologia, Institut Universitari Dexeus, Barcelona, España.

• Diamant Z, Mantzouranis E, Bjermer L. Montelukast in the treatment of asthma and beyond. Department of Allergology, Erasmus Medical Center, Rotterdam, The Netherlands.. Expert Rev Clin Immunol. 2009 Nov;5(6):639-58.

• Day JH, Briscoe MP, Ratz JD, Efficacy of levocetirizine compared with montelukast in subjects with ragweed-induced seasonal allergic rhinitis in the Environmental Exposure Unit. Department of Medicine, Queen's University and Division of Allergy and Immunology, Kingston General Hospital, Kingston, Ontario, Canada. Allergy Asthma Proc. 2008 May-Jun;29(3):304-12. Epub 2008 Apr 2.

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Introduction Research Question Methods Results DiscussionAims

References

• Nayak, Anjuli Sneeze, Wheeze and Itch Associates, Normal, Illinois, USA; Langdon, Ronald B Merck Reserch Laboratories, Rahway, New Jersey, USA; Montelukast in the Treatment of Allergic Rhinitis An Evidence-Based Review, 2007

• Nathan RA, Meltzer EO, Selner JC et al. Prevalence of allergic rhinitis in the United States. J Allergy Clin Immunol 1997,99:S808-14

• M Ciebiada, M Gorska Ciebiada, T Kmiecik, LM DuBuske, P Gorski, Quality of Life in Patients with Persistent allergic Rhinitis Treated With Montelukast alone or in combination With levocetirizine or Desloratadine, J Investig Allergol Clin Immunol 2008; Vol. 18(5): 343-349

28Introdução à Medicina II03-06-2011

Acknowledgments

Introdução à Medicina II 53

• Prof. Dr. Altamiro Costa Pereira• Prof. Dr. João de Almeida Lopes da

Fonseca• Dr. Luís Miguel Ribeiro Nogueira

Soares da Silva • Daniela Linhares

03-06-2011

Credits

• Researchers– Ana Borges– Ana Silva– Ana Costa– André Silva– Íris Silva– Mauro Pinho– Rodrigo Freitas– Sara Diniz– Sofia Carvalho– Susana Costa

• E-mail– mimedt19@gmail.com

• Regent– Prof. Altamiro Manuel

Rodrigues Costa Pereira• Advisers

– Dr. Luís Miguel Ribeiro Nogueira Soares da Silva

– Prof. Dr. João de Almeida Lopes da Fonseca

– Daniela Linhares

Introdução à Medicina II 3003-06-2011