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Tetracyclines and clindamycin plus rifampicin combination therapy are both considered first-line therapy in current Hidradenitis Suppurativa (HS) guidelines. However, evidence for their efficacy is drawn from small studies, often without validated outcomes. To assess the 12-week efficacy of oral tetracyclines and a combination of clindamycin and rifampicin. A prospective, international cohort study performed between October 2018 and August 2019. In total, 63.6% of the included 283 patients received oral tetracyclines and 36.4% were treat