Efficacy of tetracyclines and clindamycin plus rifampicin for the treatment of hidradenitis suppurativa: JAAD study

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by painful, deep-seated, inflammatory nodules and sinuses in the intertriginous areas of the body. Current guidelines for HS recommend 2 types of systemic antibiotic therapy as the first-line treatment. Oral tetracyclines like doxycycline and minocycline, are recommended as a first-line therapy for mild to moderate HS. The combination of clindamycin and rifampicin is favoured as a first-line therapy for moderate to severe HS and as second-line therapy for mild to moderate disease unresponsive to oral tetracyclines. Evidence to support the efficacy of these treatments is weak. Recently a study comparing the 12-week efficacy of oral tetracyclines and a combination of clindamycin and rifampicin was published in the Journal of American Academy of Dermatology.

This was a multicentre, international study to assess the 12-week efficacy of oral tetracyclines and a combination of clindamycin and rifampicin in patients with HS. In addition, factors associated with treatment response were noted.

A detailed protocol including study design, inclusion and exclusion criteria, HS treatment guidelines, assessment schedule, and timeline was prepared and sent out to all centres. Following this patients who were treated according to the current international guidelines with either oral tetracyclines (tetracycline 500 mg twice daily, doxycycline 100 mg once daily, minocycline 100 mg once daily) or clindamycin 300 mg twice daily in combination with rifampicin 600 mg/day in daily practice were included from 15 European centres between October 2018 and August 2019.

Patients were included in a real-life clinical practice setting without blinding or randomization. Patient characteristics (age, sex, body mass index [BMI], disease duration, first or second degree family history) were collected at baseline. Patient-reported outcome measures (PROMs) (Numerical Rating Scale [NRS] pain, NRS Pruritus, and Dermatology Life Quality Index [DLQI]), and physician scores (inflammatory nodule count, abscess count, draining sinus tract count, International Hidradenitis Suppurativa Severity Score System [IHS4], modified Sartorius score, Hurley and refined Hurley staging) were assessed at baseline and after 12 weeks of treatment. Hidradenitis Suppurativa Clinical Response (HiSCR), (50% or greater reduction in inflammatory lesion count [abscesses plus inflammatory nodules] and no increase in abscesses or draining fistulas compared with baseline) was calculated at 12 weeks.

Results

In total, 283 patients were included; 63.6% (180/ 283) patients received tetracycline treatment (tetracycline, n = 42; doxycycline, n = 121; minocycline, n = 17) and 36.4% (103/283) patients received treatment with a combination of clindamycin plus rifampicin. There were no significant differences between these 2 treatment groups. Patients treated with clindamycin and rifampicin had significantly more severe disease reflected in a significantly higher number of inflammatory nodules (P = .029) and draining sinus tracts (P = .003), higher IHS4 score (P = .019), Hurley stage (P = .004), modified Sartorius (P = .001), and NRS Pain score (P = .005) compared with patients treated with tetracycline.

Both groups showed a significant decrease in IHS4 from baseline; from a median (interquartile range) of 9.0 (5.0-18.5) to 5.0 (2.0-12.0) (P=.001) in the tetracycline group and from 13.0 (6.0-27.0) to 6.0 (1.0-17.0) (P = .001) in the combination therapy. There was no significant difference in the percentage of patients achieving HiSCR between the tetracycline group (40.1%) and the clindamycin and rifampicin group (48.2%; P = .263). HiSCR attainment was not related to Hurley stage or IHS4 category for either tetracyclines (P = .920 and P = .495) and clindamycin and rifampicin (P = .807 and P = .796).

Patients in both groups reported a significant decrease in DLQI, NRS Pain, and NRS pruritus after 12 weeks of treatment. There was no significant difference between the treatment groups regarding the percentage of patients who achieved either the MCID for NRS Pain or the MCID for the DLQI (P = .643 and P = .084, respectively). MCID pain was significantly more often achieved by patients in Hurley stage III or IHS4 severe category (respectively, P = .028 and P = .001) in the tetracycline group. No significant difference for MCID pain attainment was found in the clindamycin and rifampicin group.

Univariate regression analysis showed no significant difference between treatment with tetracycline or clindamycin and rifampicin regarding attainment of either HiSCR, MCID NRS Pain, or MCID DLQI. Baseline inflammatory nodule count was significantly associated with MCID NRS pain attainment in both the tetracycline and the combination treatment group: respectively.

Gastrointestinal adverse effects were reported by 16.4% of patients in the tetracycline group compared with 11.8% of patients in the combination treatment group (P = .346). The percentage of participants discontinuing either of the treatments because of effects did not differ significantly (P = .260). No significant associations were found for BMI, age, smoking status, discontinuation of treatment, or gastrointestinal adverse effects for either tetracycline or combination treatment.

Rifampicin has been shown to dramatically reduce plasma concentrations of clindamycin, making a meaningful contribution of clindamycin to either bacterial resistance or reduction of inflammation in this combination unlikely. A retrospective study found similar rates of HiSCR attainment between treatment with clindamycin and rifampicin compared with clindamycin alone after 8 weeks of treatment.

This study suggests that tetracyclines could be considered as the first-line treatment in patients with moderate to severe disease. This could prove especially valuable in countries with endemic tuberculosis, where rifampicin is preferably reserved for the treatment of tuberculosis or in patients with relative contraindications because of potential drug interaction. Guidelines advise that biologics (adalimumab) can be initiated after failure of conventional treatment, often clindamycin and rifampicin combination therapy. So this study indicates that failure of tetracycline treatment could be a sufficient criteria for starting biologic therapy in HS.

In conclusion, this study shows no significant difference between patients treated with tetracyclines and with a combination of clindamycin and rifampicin in hidradenitis suppurativa.

References

Van Straalen KR, Tzellos T, Guillem P, Benhadou F, Cuenca-Barrales C, Daxhelet M, Daoud M, Efthymiou O, Giamarellos-Bourboulis EJ, Jemec GBE, Katoulis AC, Koenig A, Lazaridou E, Marzano AV, Matusiak Ł, Molina-Leyva A, Moltrasio C, Pinter A, Potenza C, Romaní J, Saunte DM, Skroza N, Stergianou D, Szepietowski J, Trigoni A, Vilarrasa E, van der Zee HH. The efficacy and tolerability of tetracyclines and clindamycin plus rifampicin for the treatment of hidradenitis suppurativa: Results of a prospective European cohort study. J Am Acad Dermatol. 2021 Aug;85(2):369-378. doi: 10.1016/j.jaad.2020.12.089. Epub 2021 Jan 20. PMID: 33484766.