Asthma Update Dr Ed Cetti Consultant Respiratory Physician Spire Gatwick Park Hospital Surrey & Sussex Healthcare NHS Trust

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

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 a stepwise approach 4 4. British Guideline on the Management of Asthma. British Thoracic Society/Scottish Intercollegiate Guidelines Network Asthma /Guidelines/sign101%20revised%20June%2009.pdf

How do we apply the stepwise approach? Start treatment at the step most appropriate to initial severity 4 Start treatment at the step most appropriate to initial severity 4 Achieve early control 4 Achieve early control 4 Maintain control by stepping up treatment as necessary British Guideline on the Management of Asthma. British Thoracic Society/Scottish Intercollegiate Guidelines Network Asthma /Guidelines/sign101%20revised%20June%2009.pdf

epping down Stepping down Ensure regular review of patients as treatment is stepped down 4 Decide which drug to step down first and at what rate 4 When control is good, step down British Guideline on the Management of Asthma. British Thoracic Society/Scottish Intercollegiate Guidelines Network 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 Control?

BTS/SIGN: 1 No daytime symptoms No daytime symptoms No night time awakenings due to asthma No night time awakenings due to asthma No need for reliever medication No need for reliever medication No exacerbations No exacerbations No limitation of physical activity No limitation of physical activity Normal lung function (in practical terms FEV 1 ) and/or PEF  80% predicted or best Normal lung function (in practical terms FEV 1 ) and/or PEF  80% predicted or best GINA: 2 No daytime symptoms No daytime symptoms No nocturnal symptoms or awakenings No nocturnal symptoms or awakenings No need for reliever medication No need for reliever medication No exacerbations No exacerbations No limitations on activities No limitations on activities Normal lung function (PEF, FEV 1 ) Normal lung function (PEF, FEV 1 ) 1. BTS/SIGN British Guideline on the Management of Asthma – updated June Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) Current asthma guidelines

1.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? 2.During the past 4 weeks, how often have you had shortness of breath? 3.During the past 4 weeks, how often did your asthma symptoms (wheezing, coughing, shortness of breath, chest tightness or pain) wake you up at night, or earlier than usual in the morning? 4.During the past 4 weeks, how often have you used your rescue inhaler or nebulizer medication (such as salbutamol)? 5.How would you rate your asthma control during the past 4 weeks? Score Patient Total Score Copyright 2002, QualityMetric Incorporated. Asthma Control Test Is a Trademark of QualityMetric Incorporated. Asthma Control Test™ (ACT)

ACT Scores 25 – Well done. Asthma has been under control for last month. 25 – Well done. Asthma has been under control for last month – On Target. Asthma has been reasonably well controlled for last month – On Target. Asthma has been reasonably well controlled for last month. <20 – Off Target. Asthma may not have been controlled over last month. <20 – Off Target. Asthma may not have 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 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 puffs bd) Seretide accuhaler 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: Loke. Thorax 2011;66:

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

Allergic asthma Currently 80% of asthma expenditure goes on 20% of patients – severe asthma Currently 80% of asthma expenditure goes on 20% of patients – severe asthma 50% of severe asthmatics have ‘allergic’ asthma 50% of severe asthmatics have ‘allergic’ asthma IgE antibody has a central role in allergic inflammatory cascade IgE antibody has a central role in allergic inflammatory cascade Prevalence of asthma is closely linked to total serum IgE level Prevalence of asthma is closely linked to total serum IgE level Specific IgE antibodies correlate with ‘allergies’ Specific IgE antibodies correlate with ‘allergies’

Xolair – Omalizumab First Recombinant humanised monoclonal antibody vs. IgE Binds to all forms of IgE

INNOVATE Trial pts – 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 exacerbations 3 74% reduction in A+E visits 5 62 % reduction in Hospitalisations 5 46% improvement in Qol 7 Why wait?

Xolair Sub-cut administration every 2-4 weeks Sub-cut administration every 2-4 weeks £ £15000 per year £ £15000 per year Dependent on body-weight and IgE level Dependent on body-weight and IgE level 16 week trial for each patient - ?responder – symptoms, exacerbations, PFT, QoL 16 week trial for each patient - ?responder – symptoms, exacerbations, PFT, QoL If non-responder – stop and Novartis replaces all drug used free-of-charge If non-responder – stop and Novartis replaces all drug used free-of-charge

Xolair – anti-IgE NICE approved as add-on therapy for severe persistent allergic asthma, >12 yrs old NICE approved as add-on therapy for severe persistent allergic asthma, >12 yrs old FEV1 <80%, frequent day or night symptoms FEV1 <80%, frequent day or night symptoms IgE mediated allergy to perennial allergen, skin-prick / RAST confirmed (HDM, cat, dog, grass) IgE mediated allergy to perennial allergen, skin-prick / RAST confirmed (HDM, cat, dog, grass) 2 or more admissions with exacerbations in 12/12 or… 2 or more admissions with exacerbations in 12/12 or… 3 or more severe exacerbations in 12/12 requiring ED attendance, 1 of which led to admission 3 or more severe exacerbations in 12/12 requiring ED attendance, 1 of which led to admission

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