Asthma UpdateAsthma Update

Dr Ed CettiDr Ed CettiConsultant Respiratory PhysicianConsultant Respiratory Physician

Spire Gatwick Park HospitalSpire Gatwick Park HospitalSurrey & Sussex Healthcare NHS Surrey & Sussex Healthcare NHS

TrustTrust

Asthma Locally 5 – 6% of local population have asthma

(Incidence is one of highest in world) Approximately 2 adults per week attend ED

with acute asthma Large proportion of these are repeat

offenders DOH - >80% of these are avoidable

Approximately 1 death every 2 months from asthma – probably all avoidable

Age 13 - 85

Local Asthma Project

6 month project across 18 practices ‘At risk’ asthma patients reviewed Treatment optimised according to

guidelines

30% drop in admissions – acute asthma

Cost Effective Treatment

Patients use the right drugs at the right times through the right devices in the right way

So that: Symptoms are minimised Impact on daily life is minimised Exacerbations, Admissions and Deaths

are prevented Side-effects are minimised Costs are minimised

Variability

Degree of Asthma symptoms, airflow obstruction, inflammation varies over time

Need to increase treatment when bad

To avoid side-effects and cost, reduce treatment when good

The BTS/SIGN Guidelines recommend astepwise approach4

4. British Guideline on the Management of Asthma. British Thoracic Society/Scottish Intercollegiate Guidelines Network 2009. www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/ Asthma /Guidelines/sign101%20revised%20June%2009.pdf

How do we apply theHow do we apply thestepwise approach?stepwise approach?

Start treatment at the step most Start treatment at the step most appropriate to initial severityappropriate to initial severity44

Achieve early controlAchieve early control44

Maintain control by stepping up treatment as necessary.4

4. British Guideline on the Management of Asthma. British Thoracic Society/Scottish Intercollegiate Guidelines Network 2009. www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/ Asthma /Guidelines/sign101%20revised%20June%2009.pdf

Stepping downepping down• Ensure regular review of patients as treatment is stepped down4

• Decide which drug to step down first and at what rate4

When control is good,

step down.4

4. British Guideline on the Management of Asthma. British Thoracic Society/Scottish Intercollegiate Guidelines Network 2009. www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/ Asthma /Guidelines/sign101%20revised%20June%2009.pdf

Adults

Step 2 – Starting Point

Most symptomatic new diagnoses – start at step 2

ICS – 200mcg Beclometasone equivalent bd

Use Clenil mdi 100mcg 2 puffs bd via spacer

Alternative – Qvar Easibreathe 50mcg 2 puffs bd

Assess response – asthma control

What is Asthma What is Asthma Control?Control?

BTS/SIGN:BTS/SIGN:11

No daytime symptomsNo daytime symptoms No night time awakenings No night time awakenings

due to asthmadue to asthma• No need for reliever No need for reliever

medicationmedication• No exacerbationsNo exacerbations• No limitation of physical No limitation of physical

activityactivity• Normal lung function (in Normal lung function (in

practical terms FEVpractical terms FEV11) ) and/or PEF and/or PEF 80% 80% predicted or bestpredicted or best

GINA:GINA:22

No daytime symptomsNo daytime symptoms• No nocturnal symptoms or No nocturnal symptoms or

awakeningsawakenings• No need for reliever No need for reliever

medicationmedication• No exacerbationsNo exacerbations• No limitations on activitiesNo limitations on activities• Normal lung function Normal lung function

(PEF, FEV(PEF, FEV11))1. BTS/SIGN. 2008 British Guideline on the Management of Asthma – updated June 2009.

2. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2008.

Current asthma guidelines

1.1. In the past 4 weeks, how much of the time did your asthma keep you from In the past 4 weeks, how much of the time did your asthma keep you from getting as much done at work, school or at home?getting as much done at work, school or at home?

2.2. During the past 4 weeks, how often have you had shortness During the past 4 weeks, how often have you had shortness of breath?of breath?

3.3. During the past 4 weeks, how often did your asthma symptoms During the past 4 weeks, how often did your asthma symptoms (wheezing, coughing, shortness of breath, chest tightness or pain) (wheezing, coughing, shortness of breath, chest tightness or pain)

wake you up at night, or earlier than usual in the morning?wake you up at night, or earlier than usual in the morning?

4.4. During the past 4 weeks, how often have you used your rescue During the past 4 weeks, how often have you used your rescue inhaler or nebulizer medication (such as salbutamol)?inhaler or nebulizer medication (such as salbutamol)?

5.5. How would you rate your asthma control during the past How would you rate your asthma control during the past 4 weeks?4 weeks?

ScoreScore

Patient Total ScorePatient Total ScoreCopyright 2002, QualityMetric Incorporated.Copyright 2002, QualityMetric Incorporated.Asthma Control Test Is a Trademark of QualityMetric Incorporated.Asthma Control Test Is a Trademark of QualityMetric Incorporated.

Asthma Control Test™ (ACT)Asthma Control Test™ (ACT)

ACT ScoresACT Scores

25 – Well done. Asthma has been under 25 – Well done. Asthma has been under control for last month.control for last month.

20-24 – On Target. Asthma has been 20-24 – On Target. Asthma has been reasonably well controlled for last reasonably well controlled for last month.month.

<20 – Off Target. Asthma may not have <20 – Off Target. Asthma may not have been controlled over last month.been controlled over last month.

An ED attendance = Sub-optimal Control

If control is sub-optimal

Assess compliance Re-assess inhaler technique Reassess diagnosis Look for exacerbating factors and

treat GORD Rhinitis / Allergies Smoking Occupational exposures

Step up

Make 1 step at a time, change 1 thing Step 3 practically means stopping ICS

and starting a combination inhaler – ensures dual therapy, improves compliance

Symbicort 200/6 1 puff bd Seretide accuhaler 100 1 puff bd Seretide evohaler 50 2 puffs bd Flutiform mdi 50/5 2 puffs bd

Increasing dose at Step 3 Reassess as before Increase Symbicort / Seretide strength to

800mcg BDP equivalent Symbicort 200/6 2 puffs bd Seretide 125 evohaler 2 puffs bd Seretide 250 accuhaler 1 puff bd Flutiform 125/5 mdi 2 puffs bd

Consider Montelukast 10mg od

Step 4

Consider chest physician Reassess Increase ICS to 2000mcg: Symbicort 400/12 2 puffs bd (Seretide evohaler 250 2 puffs bd) Seretide accuhaler 500 1 puff bd Flutiform 250/10 mdi 2 puffs bd Montelukast + Uniphyllin 200mg bd

Step 5

Reassess Under Chest Physician

Good Control – Should we change anything?

Safe to step-down RCT Scotland: 259 adult asthmatics,

≥800mcg Well controlled step down vs. sham

step down No difference in exacerbation rates

Hawkins et al. BMJ 2003;326:1115

Risks of Overtreatment

Dose-response curve means benefits of increased ICS dose may be minimal

Side-effects – dysphonia, candida Purpura, skin thinning – dose response

≥400mcg/day Adrenal suppression – occurs

≥800mcg/day Osteoporosis occurs ≥800mcg/day – every

500mcg increase – 9% increase in fractures

Geddes. Thorax 1992;47:404-407

Loke. Thorax 2011;66:699-708

Costs of Overtreatment Symbicort 400/12 ii bd:£76 Seretide 250 ii bd: £59 Flutiform 250 ii bd: £46

Symbicort 200/6 ii bd: £38 Seretide 125 ii bd: £35 Flutiform 125 ii bd: £29

Symbicort 200/6 i bd: £19 Seretide 50 ii bd: £18 Flutiform 50 ii bd: £18

? Tiotropium - Step 3? Tiotropium - Step 3

Allergic asthmaAllergic asthma

Currently 80% of asthma expenditure goes Currently 80% of asthma expenditure goes on 20% of patients – severe asthmaon 20% of patients – severe asthma

50% of severe asthmatics have ‘allergic’ 50% of severe asthmatics have ‘allergic’ asthmaasthma

IgE antibody has a central role in allergic IgE antibody has a central role in allergic inflammatory cascadeinflammatory cascade

Prevalence of asthma is closely linked to Prevalence of asthma is closely linked to total serum IgE leveltotal serum IgE level

Specific IgE antibodies correlate with Specific IgE antibodies correlate with ‘allergies’‘allergies’

Xolair – Omalizumab

First Recombinant humanised monoclonal antibody vs. IgE

Binds to all forms of IgE

INNOVATE Trial 2005

419 pts – 12-75 yrs Severe persistent allergic asthma

FEV1 <80% Recent exacerbation Total IgE >30 <700 Skin prick +ve Optimised inhaled Step 3 + Xolair

vs. placebo

Xolair significantly reduces exacerbation rates by 43% in patients not receiving maintenance OCS.

Severe exacerbation rate in patients not receiving maintenance OCS.3

Xolair significantly reduces the mean number of asthma exacerbations in patients with SPAA in normal clinical practice.5

Adapted from Bleeker et al (2005)3; a subgroup analysis of INNOVATE4 comparing patients requiring OCS at baseline with those that did not.

Results from Niven & Radwan (2011); the APEX study, a retrospective review of 136 patients with severe persistent allergic asthma prescribed omalizumab as part of usual clinical practice.

In the overall INNOVATE population, when added in to standard care of high-dose inhaled corticosteroids (ICS) plus a long acting B2-agonist, XOLAIR significantly reduced severe exacerbation rate by 50% versus placebo (p=0.002).4

In the APEX study, exacerbation rates decreased significantly in both cohorts in the 12 months after omalizumab initiation, by a mean of –2.02 (±3.02) in the continuous OCS cohort (p<0.001);and by –1.78 (±2.55) in the non-continuous OCS cohort (p<0.001) −− the between-group difference was not statistically significant (0.24 [95% CI –0.79, 1.27]; p=0.6458).5

XOLAIR is well tolerated

Refer to Summary of Product Characteristics for a full list of adverse events.

• Cumulative exposure of more than 279,000 patient-years XOLAIR worldwide since first launch.8

• Adverse events in clinical trials with XOLAIR were mostly mild to moderate in severity.9

• In adult and adolescent patient age 12 years and above, the most commonly reported adverse events were injection site reactions including injection site pain swelling, erythema, pruritis and headache.8

• In children 6 to <12 years of age, the most commonly reported adverse reaction were headache, pyrexia and upper abdominal pain.8

• XOLAIR has a favourable safety profile for use in patients taking multiple medications.

Prescribe Xolair before maintenance OCS for…

43% reduction in severe exacerbations3

74% reduction in A+E visits5

62 % reduction in Hospitalisations5

46% improvement in Qol7

Why wait?

XolairXolair Sub-cut administration every 2-4 weeksSub-cut administration every 2-4 weeks £3000 - £15000 per year£3000 - £15000 per year

Dependent on body-weight and IgE levelDependent on body-weight and IgE level

16 week trial for each patient - ?16 week trial for each patient - ?responder – symptoms, exacerbations, responder – symptoms, exacerbations, PFT, QoLPFT, QoL

If non-responder – stop and Novartis If non-responder – stop and Novartis replaces all drug used free-of-chargereplaces all drug used free-of-charge

Xolair – anti-IgEXolair – anti-IgE

NICE approved as add-on therapy for severe NICE approved as add-on therapy for severe persistent allergic asthma, >12 yrs oldpersistent allergic asthma, >12 yrs old

FEV1 <80%, frequent day or night symptomsFEV1 <80%, frequent day or night symptoms IgE mediated allergy to perennial allergen, IgE mediated allergy to perennial allergen,

skin-prick / RAST confirmed (HDM, cat, dog, skin-prick / RAST confirmed (HDM, cat, dog, grass)grass)

2 or more admissions with exacerbations in 2 or more admissions with exacerbations in 12/12 or…12/12 or…

3 or more severe exacerbations in 12/12 3 or more severe exacerbations in 12/12 requiring ED attendance, 1 of which led to requiring ED attendance, 1 of which led to admissionadmission

Summary

To optimise asthma treatment need to identify those patients who need treatment changing

All those who attend ED need asthma reviewing

Remember: Compliance, technique, exacerbating factors

Allergic asthma – consider referring