29. Supplement to Reddel et
al, JACI in Practice
2022; 10: S31-s38
This template can be
modified for other ICS-
formoterol combinations
or for as-needed-only
ICS-formoterol.
The action plan on which
it is based has been
widely used in Australia
and other countries
since 2007.
SPEAKERS: Changes in GINA 2023 for adults and adolescents :
Year added at top left, to avoid use of out-of-date versions of GINA figures
Rationale for Track 1 being the preferred regimen has been updated (see details on later slides)
As-needed ICS-SABA (if available) has been added as a reliever option in Track 2 for Steps 3–5, with most of the benefit seen in Step 3
Anti-inflammatory relievers have been identified with an asterisk (see next 2 slides for details)
NOTE: in Step 5, ‘add-on LAMA’ can be combination (triple) or separate inhalers. If a patient is prescribed triple therapy with a non-formoterol LABA, the reliever should be SABA or ICS-SABA (not ICS-formoterol).
SPEAKERS:
MART was originally called SMART, with the ‘S’ coming from the brandname of the medication used in most of the studies. The ‘S’ can now stand for ‘single inhaler’, but this may cause confusion because patients may have two ICS-formoterol inhalers, one at home for their maintenance treatment, and one in their bag/pocket for as-needed doses when they are away from home.
Step 5: The dotted line for MART is to indicate that there is no evidence, in a patient taking Step 5 treatment, for switching from a SABA reliever to an ICS-formoterol reliever. However, if a patient already prescribed MART is stepped up from Step 4 to Step 5, e.g. with addition of biologic therapy, there is no need to swjtch their reliever from ICS-formoterol to SABA.
In Step 5, ‘add-on LAMA’ can be combination (triple) or separate inhalers. If a patient is prescribed triple therapy with a non-formoterol LABA, the reliever should be SABA or ICS-SABA (not ICS-formoterol).
SPEAKERS
The main benefit of using budesonide-salbutamol (ICS-SABA) as a reliever has been seen in Step 3. There is no evidence yet for safety and efficacy of budesonide-salbutamol in Steps 1–2.
Track 2 requires two inhalers. Check inhaler technique carefully if the patient’s maintenance treatment and reliever treatment are in different inhaler devices.
In Step 5, ‘add-on LAMA’ can be combination (triple) or separate inhalers.
SPEAKERS
The main benefit of using budesonide-salbutamol (ICS-SABA) as a reliever has been seen in Step 3. There is no evidence yet for safety and efficacy of budesonide-salbutamol in Steps 1–2.
Track 2 requires two inhalers. Check inhaler technique carefully if the patient’s maintenance treatment and reliever treatment are in different inhaler devices.
In Step 5, ‘add-on LAMA’ can be combination (triple) or separate inhalers.
SPEAKERS: MART was originally called SMART, with the ‘S’ coming from the brandname of the medication used in most of the studies. The ‘S’ can also stand for ‘single inhaler’, but this may cause confusion because patients may have two ICS-formoterol inhalers, one at home for their maintenance treatment, and one in their bag/pocket for as-needed doses when they are away from home.
O'Byrne PM, FitzGerald JM, Bateman ED, et al., Inhaled combined budesonide-formoterol as needed in mild asthma. N. Engl. J. Med., 2018. 378: 1865-1876.
Bateman ED, Reddel HK, O'Byrne PM, et al., As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N. Engl. J. Med., 2018. 378: 1877-1887.
Beasley R, Holliday M, Reddel HK, et al., Controlled trial of budesonide-formoterol as needed for mild asthma. N. Engl. J. Med., 2019. 380: 2020-2030.
Hardy J, Baggott C, Fingleton J, et al., Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial. Lancet, 2019. 394: 919-928.
Baggott C, Chan A, Hurford S, et al., Patient preferences for asthma management: a qualitative study. BMJ open, 2020. 10: e037491.
Baggott C, Hansen P, Hancox RJ, et al., What matters most to patients when choosing treatment for mild-moderate asthma? Results from a discrete choice experiment. Thorax, 2020. 75: 842-848.
Foster J, Beasley R, Braithwaite I, et al., Perspectives of mild asthma patients on maintenance versus as-needed preventer treatment regimens: a qualitative study. BMJ open, 2022. 12: e048537.
Foster JM, Beasley R, Braithwaite I, et al., Patient experiences of as-needed budesonide-formoterol by Turbuhaler® for treatment of mild asthma; a qualitative study. Respir. Med., 2020. 175: 106154.
Crossingham I, Turner S, Ramakrishnan S, et al., Combination fixed-dose beta agonist and steroid inhaler as required for adults or children with mild asthma. Cochrane Database Syst Rev, 2021. 5: Cd013518.
1. Papi A, Canonica GW, Maestrelli P, et al., Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N. Engl. J. Med., 2007. 356: 2040-52.
2. Martinez FD, Chinchilli VM, Morgan WJ, et al., Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet, 2011. 377: 650-7.
3. Calhoun WJ, Ameredes BT, King TS, et al., Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial. JAMA, 2012. 308: 987-97.
4. Sumino K, Bacharier LB, Taylor J, et al., A pragmatic trial of symptom-based inhaled corticosteroid use in African-American children with mild asthma. J Allergy Clin Immunol Pract, 2020. 8: 176-185.e2.
Sobieraj DM, Weeda ER, Nguyen E, et al., Association of inhaled corticosteroids and long-acting beta-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: A systematic review and meta-analysis. JAMA, 2018. 319: 1485-1496.
Cates CJ and Karner C, Combination formoterol and budesonide as maintenance and reliever therapy versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults and children. Cochrane Database Syst Rev, 2013. 4: CD007313.
Rabe KF, Atienza T, Magyar P, et al., Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet, 2006. 368: 744-53.
SPEAKERS: the addition of as-needed ICS-SABA in Track 2 was because of evidence from this RCT (MANDALA) published in 2022
1. Crossingham I, Turner S, Ramakrishnan S, et al., Combination fixed-dose beta agonist and steroid inhaler as required for adults or children with mild asthma. Cochrane Database Syst Rev, 2021. 5: Cd013518.
2. Papi A, Canonica GW, Maestrelli P, et al., Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N. Engl. J. Med., 2007. 356: 2040-52.
3. Cates CJ and Karner C, Combination formoterol and budesonide as maintenance and reliever therapy versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults and children. Cochrane Database Syst Rev, 2013. 4: CD007313.
4. Sobieraj DM, Weeda ER, Nguyen E, et al., Association of inhaled corticosteroids and long-acting beta-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: A systematic review and meta-analysis. JAMA, 2018. 319: 1485-1496.
5. Papi A, Chipps BE, Beasley R, et al., Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma. N. Engl. J. Med., 2022. 386: 2071-2083.
6. Pauwels RA, Sears MR, Campbell M, et al., Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial. Eur. Respir. J., 2003. 22: 787-94.
7. Tattersfield AE, Lofdahl CG, Postma DS, et al., Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial. Lancet, 2001. 357: 257-61.
8. Rabe KF, Atienza T, Magyar P, et al., Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet, 2006. 368: 744-53.
SPEAKERS: Changes in GINA 2023 for adults and adolescents :
Year added at top left, to avoid use of out-of-date versions of GINA figures
Rationale for Track 1 being the preferred regimen has been updated (see details on later slides)
As-needed ICS-SABA (if available) has been added as a reliever option in Track 2 for Steps 3–5, with most of the benefit seen in Step 3
Anti-inflammatory relievers have been identified with an asterisk (see next 2 slides for details)
NOTE: in Step 5, ‘add-on LAMA’ can be combination (triple) or separate inhalers. If a patient is prescribed triple therapy with a non-formoterol LABA, the reliever should be SABA or ICS-SABA (not ICS-formoterol).
Lazarinis N, Jørgensen L, Ekström T, et al., Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction. Thorax, 2014. 69: 130-136.
Duong M, Gauvreau G, Watson R, et al., The effects of inhaled budesonide and formoterol in combination and alone when given directly after allergen challenge. J Allergy Clin Immunol, 2007. 119: 322-7.
1. Papi A, Corradi M, Pigeon-Francisco C, et al., Beclometasone–formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial. Lancet Respir Med, 2013. 1: 23-31.
2. Pauwels RA, Sears MR, Campbell M, et al., Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial. Eur. Respir. J., 2003. 22: 787-94.
3. Tattersfield AE, Lofdahl CG, Postma DS, et al., Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial. Lancet, 2001. 357: 257-61.
SPEAKERS: For patients who have a history of frequent oral candidiasis, suggest rinsing mouth and spitting out after as-needed doses as well, if possible.
References:
1. Baggott C, Reddel HK, Hardy J, et al., Patient preferences for symptom-driven or regular preventer treatment in mild to moderate asthma: findings from the PRACTICAL study, a randomised clinical trial. Eur. Respir. J., 2020. 55.
2. Bousquet J, Boulet LP, Peters MJ, et al., Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone. Respir. Med., 2007. 101: 2437-46.
3. Buhl R, Kuna P, Peters MJ, et al., The effect of budesonide/formoterol maintenance and reliever therapy on the risk of severe asthma exacerbations following episodes of high reliever use: an exploratory analysis of two randomised, controlled studies with comparisons to standard therapy. Respir. Res., 2012. 13: 59.
4. O'Byrne PM, FitzGerald JM, Bateman ED, et al., Effect of a single day of increased as-needed budesonide-formoterol use on short-term risk of severe exacerbations in patients with mild asthma: a post-hoc analysis of the SYGMA 1 study. Lancet Respir Med, 2021. 9: 149-158.
5. Reddel HK, Bateman ED, Schatz M, et al., A practical guide to implementing SMART in asthma management. J Allergy Clin Immunol Pract, 2022. 10: S31-s38.
Reddel HK, Bateman ED, Schatz M, et al., A practical guide to implementing SMART in asthma management. J Allergy Clin Immunol Pract, 2022. 10: S31-s38.
Reddel HK, Bateman ED, Schatz M, et al., A practical guide to implementing SMART in asthma management. J Allergy Clin Immunol Pract, 2022. 10: S31-s38.
SPEAKERS: Changes for children 6–11 years in GINA 2023
Anti-IL5 (mepolizumab) included in Step 5 as an add-on option for children with severe exacerbation-prone eosinophilic asthma, following publication of the MUPPITS2 study (Jackson et al, Lancet 2022)
Anti-inflammatory relievers are flagged with asterisk
NOTE: ICS doses for children 6–11 years are found in Box 3-14. Doses for MART for children are in Box 3-15
SPEAKERS: Changes for children 5 years and younger in GINA 2023
Step 1: for children with infrequent viral wheezing and no or few interval symptoms, the recommendation has been clarified as “Insufficient evidence for daily controller”. Intermittent should course ICS at onset of viral illness may be considered if the physician is confident that it will be used appropriately
Moore WC, Kornmann O, Humbert M, et al., Stopping versus continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study). Eur. Respir. J., 2022. 59.
Jackson DJ, Bacharier LB, Gergen PJ, et al., Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet, 2022. 400: 502-511.
SPEAKERS: Be aware that in some languages, the word for ‘apparently’ means ‘truly’, so ‘apparently mild asthma’ would convey the opposite of the intended meaning.
References:
1. Carr TF, Fajt ML, Kraft M, et al., Treating asthma in the time of COVID. J Allergy Clin Immunol, 2023. 151: 809-817.
2. Turner S, Cotton S, Wood J, et al., Reducing asthma attacks in children using exhaled nitric oxide (RAACENO) as a biomarker to inform treatment strategy: a multicentre, parallel, randomised, controlled, phase 3 trial. Lancet Respir Med, 2022. 10: 584-592.
1. Meghji J, Mortimer K, Agusti A, et al., Improving lung health in low-income and middle-income countries: from challenges to solutions. Lancet, 2021. 397: 928-940.
2. Mortimer K, Masekela R, Ozoh OB, et al., The reality of managing asthma in sub-Saharan Africa–Priorities and strategies for improving care. Journal of the Pan African Thoracic Society, 2022. 3: 105-120.
3. Mortimer K, Reddel HK, Pitrez PM, et al., Asthma management in low and middle income countries: case for change. Eur. Respir. J., 2022. 60: 2103179.
4. Stolbrink M, Chinouya MJ, Jayasooriya S, et al., Improving access to affordable quality-assured inhaled medicines in low- and middle-income countries. Int J Tuberc Lung Dis, 2022. 26: 1023-1032.