Single-dose oral dexamethasone 10 mg without concurrent antibiotics may increase rate of symptom resolution within 48 hours in adults with acute unselected pharyngitis

EBM Focus - Volume 12, Issue 18

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Reference - TOAST trial (JAMA 2017 Apr 18;317(15):1535) (level 2 [mid-level] evidence)

  • Antibiotics are often prescribed for acute pharyngitis despite recommendations against their routine use in patients without confirmed group A streptococcus infection. Corticosteroids may reduce symptoms in patients seeking treatment beyond over-the-counter medications, but evidence for corticosteroids without concurrent antibiotic therapy is lacking.
  • In the TOAST trial, 565 adults with acute pharyngitis with suspected infectious etiology but not requiring immediate antibiotic therapy were randomized to dexamethasone 10 mg orally once vs. placebo.
  • Dexamethasone was associated with a moderately increased likelihood of complete symptom relief at 48 hours (in 35.4% vs. 27.1%, 95% CI for risk difference 1.2% to 16.2%), but there were no significant differences in the likelihood at 24 hours, median time to symptom resolution, or most other outcomes.

Acute pharyngitis is a common complaint that is usually benign and self-limiting (Ann Intern Med 2016 Mar 15;164(6):425). Guidelines recommend against routine antibiotic use in patients without confirmed group A streptococcus infection (Clin Microbiol Infect 2012 Apr;18 Suppl 1:1, NICE 2008, Ann Intern Med 2016 Mar 15;164(6):425); however, antibiotics are often prescribed (BMJ Open 2014 Oct 27;4(10):e006245, Fam Pract 2015 Aug;32(4):401). A single dose of corticosteroids is a possible non-antibiotic option to reduce inflammation and pain, but most evidence assessing its efficacy includes patients taking concurrent antibiotics (Cochrane Database Syst Rev 2012 Oct 17;(10):CD008268). To assess the effect of corticosteroids on pain, the recent TOAST trial randomized 565 adults (median 34 years old) who presented to a primary care practice for acute pharyngitis to dexamethasone 10 mg orally once vs. placebo. In 96% of cases, patients reported their symptoms to be moderate-to-severe. All cases had a suspected infectious etiology but were judged to not require immediate antibiotic therapy. However, 40% of patients were offered a delayed antibiotic prescription, to be filled in 48 hours if symptoms did not improve. Rapid streptococcal antigen tests were not available to inform treatment, but culture results were positive for streptococcus (most commonly Group A) in 16.7% of the 502 patients with available data. Over-the-counter medications were allowed. Follow-up was achieved via telephone interview or text message.

Complete symptom resolution within 48 hours was reported in 35.4% of patients taking dexamethasone vs. 27.1% with placebo (95% CI for risk difference 1.2% to 16.2%, NNT 12), with consistent findings in patients who were not offered a delayed antibiotic prescription. The risk difference in patients who were offered a delayed antibiotic prescription favored dexamethasone but was not statistically significant. Dexamethasone was also associated with a non-significantly greater likelihood of complete symptom resolution within 24 hours (22.6% vs. 17.7%, 95% CI for risk difference -1.8% to +11.2%). There were no statistically significant differences between groups in median time to onset of pain relief (27.5 vs. 27 hours), median time to complete symptom resolution (65.8 vs. 60 hours), pain severity, or serious adverse events (2 with dexamethasone and 3 with placebo).

This trial demonstrates that a single dose of dexamethasone 10 mg orally may lead to an increased likelihood of symptom resolution within 48 hours in adults with acute pharyngitis. Unlike previous trials, this trial focused exclusively on corticosteroid use without concurrent antibiotics. The effect is moderate, the confidence interval in risk difference includes clinically unimportant differences, and the effect was not significant at 24 hours. However, the confidence intervals also include larger effects, and the direction of benefit is consistent with the beneficial effect of corticosteroids in numerous smaller trials (Cochrane Database Syst Rev 2012 Oct 17;(10):CD008268). Given the common occurrence of this condition, the relative simplicity of single-dose oral corticosteroids, and concerns over antibiotic overprescription, this trial lends support to considering single-dose corticosteroids for acute pharyngitis.

For more information, see the Steroids for pharyngitis topic in DynaMed Plus. DynaMed users click here.