We treat a lot of patients with asthma in the ER, and a lot of times our patients have trouble following up with their PCP, establishing care with a new PCP, or even getting insurance. Usually, we discharge patients with just a short-acting beta-agonist (SABA) inhaler like albuterol and possibly a separate inhaled corticosteroid (ICS), but maybe we should consider prescribing combined ICS and long-acting beta-agonist (LABA) inhaler.
Guidelines and Evidence
Global Initiative for Asthma (GINA) recommends symptom-driven treatment or daily ICS-containing inhalers to reduce severe exacerbation risks
Formoterol is a LABA with a rapid onset, suitable for both maintenance and rescue therapy
Multiple studies were done with low dose ICS and combination therapies
Low-dose ICS in mild asthma reduces severe exacerbations by ~50%, improves symptom control, and enhances quality of life (Reddel 2019 or SYGMA-2)
Fixed-dose LABA/ICS used as needed is as effective as regular ICS, reducing hospital visits and daily ICS exposure without increasing adverse events (Crossingham 2021)
Budesonide/formoterol improves oxygen saturation, peak expiratory flow rate, and reduces respiratory rates post-treatment (Chew 2012)
Caveat: Noninferiority Study Design
SYGMA-2 was initially designed as a superiority trial but was later reclassified as a noninferiority trial without clear justification or protocol amendments
The trial set a noninferiority margin of 20% (rate ratio of 1.2), meaning the as-needed ICS-formoterol regimen could be up to 20% less effective than the standard therapy and still be considered noninferior. The 95% confidence interval for the primary outcome was 0.97 to 1.16, approaching the noninferiority threshold, suggesting a potential risk of inferiority in broader clinical practice.
Noninferiority does not mean similarity, the trial's design and outcomes need to be carefully interpreted especially when informing global guidelines
Conflict of Interest Concerns
While investigators collected the SYGMA-2 trial data, the analysis was conducted by employees of the sponsoring pharmaceutical company
All but two authors disclosed receiving support from the sponsor. Notably, one author served on the Board and Science Committee of GINA. Although these conflicts were declared, the article does not specify how they were addressed or mitigated
Close ties between study authors and the sponsor raise questions about the impartiality of the evidence informing the GINA guidelines
The study outcomes and guideline recommendations that favor the sponsor's product is now called into question
Benefits of Discharging with ICS-LABA (e.g., Symbicort)
Formoterol’s rapid onset makes it suitable as a rescue medication even though it is a LABA
Improves adherence by simplifying to one inhaler for both rescue and maintenance
Suggested Prescription: Budesonide/formoterol 80/4.5 μg per puff. Maintenance: 1-2 puffs once or twice daily OR Rescue: 1-2 puffs every 2-4 hours as needed for symptoms
Of note, Symbicort is NOT FDA approved as a rescue inhaler
Cost of Symbicort Without Insurance
The out-of-pocket cost for Symbicort can be substantial:
Brand-name Symbicort (80/4.5 mcg): Approximately $344.41 for a 30-day supply.
Generic versions: Around $232.12 for the same dosage.
Authorized generic (Breyna): Approximately $206.71.
Some pharmacies offer Symbicort for as low as $97.09 with a GoodRx coupon
As of June 1, 2024, AstraZeneca has capped the out-of-pocket cost of Symbicort at $35 per month for both insured and uninsured patients (with possible limitations)
Prior Authorizations and Alternative
Obtaining prior authorization (PA) for medications like Symbicort from the ED is not feasible due to the complex process:
Verify the patient's insurance coverage and determine if Symbicort requires prior authorization
Access and fill out the required PA forms found on the insurance provider's website
Send the completed forms to the insurance company via their preferred method (fax, online portal, etc.)
Follow the status of the PA request and provide any additional information if requested
The other way is to refer your patients and their family members to this site:
They can obtain a card that caps the cost of Symbicort at 35$ with a valid prescription
Takeaways
There's evidence supporting the use of ICS-formoterol as both maintenance and rescue therapy, however due to COI and dubious study design the recommendations are called into question
For patients discharged from the ED with mild to moderate asthma exacerbations, consider prescribing combined ICS/LABA instead of separate albuterol and ICS after shared decision making with patient and family
Educate your patients on the capped cost of Symbicort and possibly send them with a prescription and a savings card
References:
A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks Chew KS, Kamarudin H, Hashim CW. A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks. Int J Emerg Med. 2012;5:16. Published 2012 Apr 13. doi:10.1186/1865-1380-5-16 PMID: 22503137
Budesonide/formoterol versus salmeterol/fluticasone for asthma in children: an effectiveness and safety analysis. Jiang P, Zhao L, Yao Z. Budesonide/formoterol versus salmeterol/fluticasone for asthma in children: an effectiveness and safety analysis. J Comp Eff Res. 2021;10(17):1283-1289. doi:10.2217/cer-2021-0142 PMID: 34668718
Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review. Crossingham I, Turner S, Ramakrishnan S, et al. Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review. BMJ Evid Based Med. 2022;27(3):178-184. doi:10.1136/bmjebm-2021-111764 PMID: 34282031
GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents Reddel HK, FitzGerald JM, Bateman ED, et al. Eur Respir J. 2019;53(6):1901046. doi: 10.1183/13993003.01046-2019. PMID: 31249014