ARIA 1999-2014 and beyond

1- ARIA
2- Update
3- Revision
4- Representativity of RCTs
5- Real life studies
6- AIRWAYS ICPS

The ARIA initiative was developed

as a state-of-the-art for the specialist, the general

practitioner and for health care workers:

to update their knowledge of allergic rhinitis,

to highlight the impact of allergic rhinitis on asthma,

to provide an evidence-based documented revision on

the diagnosis methods,

to provide an evidence-based revision on the

treatments available,

to propose a stepwise approach to the management of the

disease,

to assess the magnitude of the problem in developing

countries and to implement guidelines (with IUATLD)

ARIA programme
First phase:
Development of evidence-based guidelines during a
workshop held at WHO in December 1999 (J Allergy Clin
Immunol, suppl, Nov 2001).
Document has been endorsed by several allergy,
respiratory, ENT and paediatric associations.

Second phase:
To produce materials to help improve delivery of care to
those with rhinitis. In particular a pocket guide
To implement ARIA guidelines
To make recommendations for health care professionals
(e.g. pharmacists)

ARIA pocket guide

52 translations

ARIA 1999-2014 and beyond

1- ARIA
2- Update

ARIA update
In collaboration with WHO, GA2LEN, AllerGen
First phase: Development of evidence-based
documents on:
1.

Alternative and Complementrary Medicine (Passalacqua, JACI, 2005)

2.

Allergen avoidance (Custovic & Gerth van Wijck, Allergy, 2005)

3.

Pharmacologic treatment and anti-IgE (Bousquet, Allergy, 2006)

4.

Sports and exercise (Bonini, Allergy, 2006)

5.

Specific immunotherapy (Passlacqqua & Durham JACI, 2007)

6.

Links between rhinitis and asthma (Cruz, Allergy, 2007)

7.

Mechanisms of rhinitis (Pawankar & Mullol, submitted)

Second phase:

Compile all evidence into a single document

Statement of evidence
Shekelle et al, BMJ 1999

Ia

meta-analysis of randomised controlled trials

(RCT)

Ib at least one RCT

IIa at least one controlled study without

randomisation

IIbat least one other type of study

III non-experimental descriptive studies
IV expert committee reports
or opinions
or clinical experience of respected authorities

Statement of evidence: Strength of

evidence
Shekelle et al, BMJ 1999

A category I evidence
B category II evidence or extrapolated
recommendation from category I evidence

C category III evidence or extrapolated

recommendation from category I or II evidence

D category IV evidence or extrapolated

recommendation from category I, II or III evidence

Strength of evidence for treatment of rhinitis

ARIA 2008
Intervention

SAR
PAR
PER
adult children adult children

oral anti-H1

intranasal anti-H1

intranasal CS

A**

intranasal cromone

anti-leukotriene

A (>6)

subcutaneous SIT

A**

sublingual / nasal SIT A

A**

allergen avoidance

A*

B*

A**

*: not effective in the general population, **: extrapolated from studies in SAR/PAR

Check for asthma

especially in patients with severe
and/or persistent rhinitis

Diagnosis of allergic rhinitis

Intermittent
symptoms

Mild
Not in preferred order
oral H1 blocker
or intranasal H1-blocker
and/or decongestant
or LTRA*

Moderatesevere

Persistent
symptoms
Moderatesevere

Mild

Not in preferred order

oral H1 blocker
or intranasal H1-blocker
and/or decongestant
or intranasal CS
or LTRA*
(or chromone)

In preferred order
intranasal CS
H1 blocker or LTRA*
Review the patient
after 2-4 wks

Improved
In persistent rhinitis
review the patient
after 2-4 wks
If failure: step-up
If improved: continue
for 1 month

Step-down
and continue
treatment
for > 1 month

Add or increase
intranasal CS
dose

Failure
Review diagnosis
Review compliance
Query infections
or other causes

Rhinorrhea
add ipratropium

Blockage
add
decongestant
or oral CS
(short term)

Failure
referral to specialist

Allergen and irritant avoidance may be appropriate

If conjunctivitis
Add
oral H1-blocker
or intraocular H1-blocker
or intraocular cromone
(or saline)

Consider specific immunotherapy

ARIA update
In collaboration with WHO, GA2LEN, AllerGen
First phase: Development of evidence-based
documents based on GRADE
Second phase: from recommendation to guideline
Third phase:

Translation of documents

Development of pocket guides for physicians (specialists

and primary care)

Implementation:
Europe: in collaboration between EAACI and ARIA

ARIA 1999-2011 and beyond

1- ARIA
2- Update
3- Revision

From EBM to recommandations

Brozek et al, Allergy, 2011

The strength of evidence based on

efficacy is insufficient
Importance of the GRADE (Grading
Recommendation, Assessment,
Development and Evaluation)

GRADE
Schunemann et al, Am J Respir Crit Care Med 2006
Clarity of risk/benefit

Quality of supporting evidence

Implications
Factors that may decrease the quality of evidence
Small size studies
Poor quality of planning, randomization
Biases
Inconsistency of results

Factors that may increase the quality of evidence

Large magnitude of effect
Dose-dependent gradient

GRADE of recommend ation

Schunemann et al, Am J Respir Crit Care Med 2006
High quality evidence: recommendation can apply to most
patients in most circumstances, further research is unlikely
to change recommendation
Moderate quality evidence: recommendation can apply to most
patients in most circumstances, further research may
change recommendation
Low quality evidence: recommendation may change when new
evidence is available
Very low quality evidence: recommendation may change when
new evidence is available, very uncertain

GRADE
Schunemann et al, Am J Respir Crit Care Med 2006
Grade of recommendation:
Strong: benefits clearly outweight risk and burden, or
vice versa
Weak: Benefits closely balanced with harm and burden

ARIA revision
Brozek et al, J Allergy Clin Immunol 2010
Prevention Rhinitis

Rhinitis +
asthma

11

39

Strong

Moderate

Weak

11

Very weak

16

Strong

Weak

33

Number of
analyses
Evidence level

Recommendation

Quality of guidelines (AGREE II)

Padjas et al, J Allergy Clin Immunol 2013

ARIA 1999-2014 and beyond

1- ARIA
2- Update
3- Revision
4- Representativity of RCTs

Representativity of patients with allergic rhinitis

Enrolled in RCTs
Costa D et al, J Allergy Clin Immunol 2011
311 patients seen by 48 general practitioners during grass pollen
season
Only 7.4% (95% confidence interval: 4.5-10.3%) of the patients
would have been enrolled in the RCTs.

Reasons for failure: Pareto chart

Bousquet et al, Allergy 2003

Representativity of patients with allergic rhinitis

Enrolled in RCTs
Bousquet PJ et al, submitted
311 patients seen by 48 general practitioners during grass pollen
season
Only 7.4% (95% confidence interval: 4.5-10.3%) of the patients
would have been enrolled in the RCTs.
The primary reasons for this difference were: diagnosis of
allergy by skin tests and/or serum-specific IgE (20.4%), severity
of allergic rhinitis (11.5%), other chronic diseases (11.4%), history
of sinusitis (10.4%) and asthma comorbidity (10.1%).
A sensitivity analysis excluding contraception and the diagnosis
of allergy showed that the percentage of representative patients
increased to 20.2% (15.8-24.7).

ARIA 1999-2014 and beyond

1- ARIA
2- Update
3- Revision
4- Representativity of RCTs
5- Real life studies

Validation of rhinitis guidelines

Aims
Bousquet et al, Allergy 2003

Study in seasonal allergic rhinitis

To assess whether simple guidelines based on
the International Consensus Report
- are more effective than free treatment
- can be used easily by general practioners
- in three different countries

Validation of rhinitis guidelines

Assessment of severity and treatment
oral
H1-blocker
+ topical ICS

oral
H1-blocker
0
0

10

10

10

10

ocular
nedocromil

Rhinorrhea
Obstruction
Sneezing
Conjunctivitis

Validation of rhinitis guidelines

RQLQ total score
Bousquet et al, Allergy 2003

mean total RQLQ score

consensus

free treatment

day 0

day 7

day 21

Validation of ARIA guidelines

Bousquet et al, AAAAI 2004

Study in intermitent and persistent allergic

rhinitis during pollen season
ENT specialists and allergists
France
924 patients
To assess whether ARIA guidelines based on
VAS is more effective than free choice
treatment

Validation of ARIA guidelines

Classification of patients
moderate
severe
rhinitis

mild rhinitis

10 cm

all nasal symptoms

Duration:

< 4 days/ week or < 4 consecutive weeks:

intermittent

> 4 days/week and > 4 consecutive weeks:

persistent

Validation of ARIA guidelines in specialists

4,5
free
treatment
choice

4
3,5
3
2,5

ARIA

2
1,5
1
0,5
0

baseline

2 wks

% patients with impairment

RQLQ global score (mSD)

Bousquet et al, AAAAI 2004

35
30
25
20
15
10
5
0

sleep

daily work
activities

ARIA 1999-2014 and beyond

1- ARIA
2- Update
3- Revision
4- Representativity of RCTs
5- Real life studies
6- AIRWAYS ICPs

AIRWAYS ICPs

(Eur Respir J 08-2014)

AIRWAYS-ICPs
1Collate existing ICPs, national programmes and
guidelines
used in the EU and other countries
2Use th WHO appraoch for CRDs in low and
middle income countries
3Develop a common approach for the control and
severity of
NCDs
4Develop relevant questions for CRDs in the
elderly
5Develop Integrated Care Pathways for rhinitis/
asthma
comorbidity and asthma/COPD (elderly)
6-

Develop a sentinel network for airway diseases

7-

Understand AHA across the life cycle

8-

Dissemination and scaling up

From guidelines to ICPs

ICPs differ from practice guidelines as

they are utilized by a multidisciplinary team
have a focus on the quality and co-ordination of care
ICPs need to have a mechanism for recording variations/deviat
from planned care
An ICP is intended to act as a guide to treatment.
Clinicians are free to exercise their own professional judgment
as appropriate. However, any alteration to the practice ide
within this ICP must be noted as a variance
The resulting analysis can be used to amend the ICP itself if,
for the majority of patients, the practice is different
to the pathway

Variance analysis in ARIA

Any alteration to the practice identified with the guideline

must be noted as a variance.

ARIA classification: severity (mild vs moderate/severe) is linke

with quality of life (RQLQ)
ARIA classification:
Persistence is not associated with RQLQ
Persistence is associated with prediction of efficacy
Persistence is associated with duration of treatment
Persistence is associated with asthma comorbidity
Most patients consulting in primary or secondary care
Have moderate/severe disease
Receive ICS + antihistamines

AIRWAYS-ICP: ICPs for allergic rhinitis

and asthma co-morbidity
Patient with allergic rhinitis symptoms
Self-management

Pharmacist
Incorrect
diagnosis
Severity

Improvement
OTC medication
Failure

Primary care
Incorrect
diagnosis
Severity

Improvement
Treatment
Failure

Specialist
Emergency care

(asthma)

AIRWAYS-ICP: From rhinitis to asthma

Assess
control
by VAS

Rhinitis

Assess asthma

National asthma campaign (NA

questionnaire
Have you had an attack or
recurrent attacks of wheezing?

Unknown asthma

Diagnosed asthma

Have you have a troublesome

cough especiallly at night?

Ask
Ask for
for
asthma
asthma
questio
questio
ns
ns

Assess
asthma
control

Do you have cough or wheeze

after exercise?

No asthma

Asthma

Does your chest feel tight?

Several asthma control

Questionnaires are available

AIRWAYS-ICP: From asthma to rhinitis

Asthma

Assess
asthma
control

Assess Rhinitis

Unknown rhinitis

Diagnosed rhinitis

Ask
Ask for
for
ARIA
ARIA
questio
questio
ns
ns
No rhinitis

Rhinitis

ARIA questionnaire

Symptoms suggestive of allergic rhinit

One or more of the following symptom
For >1 hr on most days
Watery rhinorrhea
Nasal obstruction
Nasal pruritus
Conjunctivitis

Symptoms which are not usually assoc

With allergic rhinitis
unilateral symptoms
mucopurulent rhinorrhea
post nasal drip
pain
recurrent epistaxis
anosmia