Ductal lavage followed by observation versus oral corticosteroids in idiopathic granulomatous mastitis: A randomized trial

Abstract

Oral corticosteroids represents the most prevalent treatment for idiopathic granulomatous mastitis. Ductal lavage with triamcinolone acetonide and antibiotics followed by observation (DL-OBS) has emerged as a novel strategy, but a comparison of them remains lacking. Here in this multicenter, open-label, non-inferiority, randomized trial (ClinicalTrials.gov identifier: NCT03724903), we assigned 140 patients to oral corticosteroids (N = 71) and DL-OBS (N = 69), stratified by baseline M-score. The primary outcome is complete Clinical Response rate at 1 year. The non-inferiority margin is -15%. The primary outcome is 85.5% in DL-OBS and 87.3% in oral corticosteroids (difference: -1.8%; 95%CI, 13.2 to 9.5; P_{non-inferiority} = .01) in intention-to-treat population, and 92.6% vs 98.2% (difference -5.6%; 95%CI -13.4 to 2.2; P_{non-inferiority} = .01) in per-protocol population, respectively. The most common (>15%) adverse events were Cushingoid, epigastric pain and arthralgia in oral corticosteroids, and irregular menstruation in DL-OBS, respectively. Here, we report that DL-OBS shows similar efficacy to oral corticosteroids but with better safety profile.

Fig. 1. Flow of participants in the study of ductal lavage followed by observation versus oral corticosteroids among patients with idiopathic granulomatous mastitis.

Abbreviation: IGM, idiopathic granulomatous mastitis; DL-OBS, ductal lavage followed by observation. Some patients had more than one reason for screening failure, including: received pertinent treatment previously (n = 41), unsuitable physical or mental condition (n = 31), exclusion based on clinical or pathological evidence (n = 23), history of breast trauma (n = 7), M-score less than 2 (n = 7), bilateral mastitis (n = 6), ineligible age or gender (n = 6) and grade III inverted nipple (n = 4). Randomization was stratified by baseline M-score. Of those who had protocol violation: received oral corticosteroids (n = 6), received repeated ductal lavage (n = 2), and received surgery treatment (n = 1) in DL-OBS group; received ductal lavage (n = 2), received repeated oral corticosteroids (n = 1), and received surgery treatment (n = 1) in oral corticosteroids group before reaching complete Clinical Response.

Fig. 2. Treatment-related adverse events in the safety population.

Abbreviations: DL-OBS, ductal lavage followed by observation. The data were reported as counts (percentage). Counts represent the number of patients who experienced at least one corresponding adverse event during the 1-year follow-up period. Besides, one patient could have more than one adverse event. In the DL-OBS group, there were 6 patients who experienced Cushingoid symptoms, 2 had irregular menstruation, and 1 developed rash after additional oral corticosteroids treatment. In the oral corticosteroids group, 1 patient experienced irregular menstruation following additional ductal lavage treatment, 1 reported headache and alopecia after ductal lavage and anti-tuberculosis treatment, 1 experienced back pain due to personal reasons, and 1 developed rash after discontinuing oral corticosteroids and undergoing surgery. Therefore, these adverse events were considered as having no definite association with the treatments assigned. All adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Source data are provided as a Source Data file. Cushingoid included the following symptoms: moon face, buffalo hump obesity, weight gain, edema, hirsutism, skin striation, and acne. Surgical-related disorders included bleeding, post-bleeding, allergy, nipple ischemia or necrosis, and thrombosis.

Fig. 3. Ductal lavage related pain score evaluated by visual analogue scale in ductal lavage followed by observation group.

Over the total five ductal lavage sessions, the missing records were caused by the following reasons: rejected to receive randomized ductal lavage followed by observation (n = 2), suspicious allergy (no records at all, n = 1; only recorded session 1, n = 1), only received 2 sessions since feeling alleviation of symptoms (n = 1), only received 3 sessions due to personal reason (n = 1), and missing recording of session 2 (n = 1). Source data are provided as a Source Data file.

Fig. 4. Exploratory analyses of the associations between the baseline levels of ESR, CRP, and NLR and time to first complete clinical response.

Abbreviations: ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; NLR, neutrophils to lymphocytes ratio; cCR, complete Clinical Response. Box plot comparing (a) ESR, (b) CRP, and (c) NLR levels between patients who achieved their first complete clinical response within Visit 1/2 or after Visit 1/2. The boxplots show the interquartile range (IQR) for the values distribution of each group, with the middle lines of the boxes indicating the median values. The whiskers represent the 1.5$\times$IQR, and points beyond the upper or lower bounds of the box represent the outliers. Source data are provided as a Source Data file. Given the disparities in laboratory testing equipment performance, specific CRP levels were unattainable in some testing sites when they fell within the normal range. Therefore, these results with approximate range were not included in the exploratory analysis (CRP < 5 mg/L: n = 2, CRP < 10 mg/L: n = 2).