For the past 25 years, most asthma guidelines have consistently recommended treatment according to level of baseline symptom frequency. Patients with intermittent symptoms (2 days or fewer per week) are generally prescribed a SABA, while only patients with so-called persistent asthma are eligible for ICS therapy.

The findings from the recent post-hoc analysis of the START study, published in the Lancet, challenge long-standing assumptions about the risks of so-called mild asthma. The study suggests that decisions about ICS treatment in such patients should be made on the basis of population risk reduction, rather than only on symptom frequency. 

In the interview below, Prof. Michils from ULB Erasme shares his opinion on the risk of exacerbations of mild symptomatic asthma patients and on different treatment strategies for these patients.

For the past 25 years, most asthma guidelines have consistently recommended treatment according to level of baseline symptom frequency. Patients with intermittent symptoms (2 days or fewer per week) are generally prescribed a SABA, while only patients with so-called persistent asthma are eligible for ICS therapy.

The findings from the recent post-hoc analysis of the START study, published in the Lancet, challenge long-standing assumptions about the risks of so-called mild asthma. The study suggests that decisions about ICS treatment in such patients should be made on the basis of population risk reduction, rather than only on symptom frequency.

This slide kit provides more details on this recent publication from the Lancet.

Helen K Reddel, William W Busse, Søren Pedersen, Wan C Tan, Yu-Zhi Chen, Carin Jorup, Dan Lythgoe, Paul M O’Byrne et al. Lancet 2017; 389: 157–66

• Conventionally, ICS treatment is recommended for patients with symptoms on more than 2 days per week, but this criterion has scant evidence.
• It is unclear whether patients with less frequent asthma symptoms benefit from ICS treatment, or whether there is evidence to support the present symptom-based criteria for initiating ICS. 
• This study is the first to assess the validity of the previous symptom-based cut-off for starting ICS by assessing the effects of budesonide versus placebo for severe asthma exacerbations, lung function, and asthma symptom control in patients with different symptoms frequency.
  

• Post-hoc analysis of the 3-year inhaled Steroid Treatment As Regular Therapy (START) study conducted in 32 countries.
• 7138 mild asthma patients randomised to receive once daily inhaled budesonide (400 µg or 200 µg if aged <11 years) or placebo.
• Coprimary outcomes: time to first severe asthma-related event (SARE; hospital admission, emergency treatment, or death) and change from baseline in lung function after bronchodilator.
• Key exclusion criteria: Asthma symptoms or treatment for more than 2 years before enrolment, more than 30 days of treatment per year with a corticosteroid, prebronchodilator FEV1 of less than 60% predicted, postbronchodilator FEV1 of less than 80% predicted.
• Interaction with baseline symptom frequency was investigated:
  • Group of patients 1: 0 to 1 symptom days per week (31%)
  • Group of patients 2: >1 to ≤2 symptom days per week (27%)
  • Group of patients 3: >2 symptom days per week (43%)
    

Across all 3 symptoms frequency groups and irrespective of baseline symptom frequency:

• Time to first severe asthma-related event (SARE) was prolonged

• Decline in postbronchodilator lung function at 3 years’ follow-up was reduced
• Severe exacerbations requiring oral or systemic corticosteroids were reduced
  

• Symptom-free days were increased   
  Similar results were noted when participants were classified by any guidelines criterion as so-called persistent versus so-called intermittent asthma.

• These findings challenge long-standing recommendations that asthma should be treated with SABA alone if the patient has symptoms ≤2 days per week.
• But mild symptomatic patients might be more mindful of their (infrequent) symptoms than the remote risk of an exacerbation and be poorly adherent to a daily ICS treatment.
• An alternative risk-reduction strategy, with as-needed ICS intake driven by concomitant β2-agonist for symptom relief, is already of substantial interest, would also address concern about side-effects, could address poor adherence as well, and might be more acceptable to clinicians and patients for mild asthma than regular daily ICS.
  

^{Reference:
Helen K Reddel, William W Busse, Søren Pedersen, Wan C Tan, Yu-Zhi Chen, Carin Jorup, Dan Lythgoe, Paul M O’Byrne et al. Lancet 2017; 389: 157–66}

NS ID XL-0397-RD07/2018-LB Local code 688