3-Week Azithromycin Shows Equivalent Efficacy to 6-Week Doxycycline for MGD

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The reduced dosing of azithromycin supports its use as an alternative to doxycycline for at least 6 weeks in patients with moderate to severe meibomian gland dysfunction.

New results from a randomized clinical trial suggest the efficacy of a 3-week course of weekly oral azithromycin was equivalent to a 6-week course of daily oral doxycycline for the signs and symptoms of moderate to severe meibomian gland dysfunction (MGD).1

The investigative team at Chiang Mai University in Thailand suggested the evidence of equivalency of both treatments at reducing the MGD and Ocular Surface Disease Index (OSDI) score at both the 6- and 8-week follow-ups, with no additional gastrointestinal adverse events (GIAEs) in the azithromycin group.

“The reduced dosing of azithromycin supports its use as an alternative to doxycycline for at least 6 weeks,” wrote corresponding author Chulaluck Tangmonkongvoragul, MD. “However, longer-term follow-up in each group would be needed to determine if these outcomes persist for this chronic condition.”

Data on global prevalence of MGD indicate a rate of 35.8%, with a more common prevalence among East Asian people (51.2%), including Thai individuals (46.2%). Common recommendations for treatment include a 6-week course of oral doxycycline, but frequent gastrointestinal adverse events (GIAEs) can impact therapy compliance. An alternative treatment for MGD, azithromycin has been reported to have a longer tissue half-life and less common GIAEs comparatively.

Tangmonkongvoragul and colleagues conducted a double-masked randomized clinical trial at a tertiary center in Thailand from September 2018 to May 2022 to compare the effects of a 3-week course of weekly oral azithromycin with a 6-week course of oral doxycycline for the management of MGD. Those eligible for study inclusion were randomized 1:1 to receive 6 weeks of oral doxycycline (100 mg twice a day) or oral azithromycin (1 g oral weekly for 3 weeks). In order to achieve full masking, investigators used a double-dummy technique to ensure the number of pills taken per day in each group was equal.

The primary objective of the study was to examine the equivalence in effects of azithromycin and doxycycline in reducing the MGD score and OSDI score at 6 and 8 weeks after initiating therapy, with secondary objectives comparing the incidence of GIAE between patients in each study arm. The total MGD score was calculated as the sum of the objective and subjective scores, while the OSDI contained 12 items (score 0 to 100). Prespecified equivalence margins for MGD score and OSDI score were set at ±2 and ±9, respectively, according to investigators.

The study population consisted of 137 eyes from 137 patients (female, 66.4%; mean age, 62.0 years), of which 68 eyes were randomized into the azithromycin arm and 69 study eyes into the doxycycline arm. There were no differences identified between groups in sex, age, stage of MGD, or baseline MGD and OSDI scores.

Investigators indicated the attention-to-treat analysis of the changes in scores using multiple imputation showed that both drug regimens were effective in treatment of MGD. Upon analysis, the adjusted mean differences of total MGD score at 6 weeks and 8 weeks between azithromycin and doxycycline were –0.33 (95% confidence interval [CI], –1.70 to 1.03; P for equivalence = .01) and 0.13 (95% CI, –1.59 to 1.84; P for equivalence = .02), respectively. Changes in MGD score of both regiments were greater than the minimal clinically important difference (MCID) of ±2 at both time points, according to the analysis.

Moreover, both treatments had similar effect in reducing OSDI score at both visits, with data showing a score of –1.20 (95% CI, –5.31 to 2.91; P for equivalence <.001) at 6 weeks and –1.59 (95% CI, –5.73 to 2.55; P for equivalence <.001) at 8 weeks, respectively. However, investigators noted the changes in OSDI score in each treatment group were less than the MCID of ±9 at both time points.

The incidence of GIAEs including nausea vomiting, dyspepsia, abdominal cramping, and decreased appetite were lower in the azithromycin group (3 of 68 cases [4.4%]; 95% CI, 0.9% - 12.4%), compared with the doxycycline group (11 of 69 cases [15.9%]; 95% CI, 8.2% - 26.7%; risk difference, 11.5%; 95% CI, 1.6% – 21.4%; P = .03). Despite the higher rate of GIAEs in those treated with doxycycline, treatment compliance was similar in each group.


  1. Upaphong P, Tangmonkongvoragul C, Phinyo P. Pulsed Oral Azithromycin vs 6-Week Oral Doxycycline for Moderate to Severe Meibomian Gland Dysfunction: A Randomized Clinical Trial. JAMA Ophthalmol. Published online March 23, 2023. doi:10.1001/jamaophthalmol.2023.0302