Dual Targeted Therapy for Hidradenitis Suppurativa: A Narrative Review

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that causes significant physical and psychosocial burden. Although U.S. Food and Drug Administration (FDA)-approved biologic therapies targeting tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) have improved outcomes for many patients with moderate-to-severe HS, a subset remain refractory or experience loss of response over time. Transcriptomic and immunologic studies demonstrate concurrent activation of multiple inflammatory pathways in HS, including TNF-α, IL-1, IL-17, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, supporting a rationale for dual targeted therapy (DTT). This narrative review summarizes the current evidence on DTT in HS and contextualizes these findings with data from other immune-mediated diseases such as inflammatory bowel disease, psoriasis, psoriatic arthritis, and rheumatoid arthritis. Published HS-specific reports remain limited to case reports of dual biologic or biologic plus Janus kinase (JAK) inhibitor therapy, each showing clinical improvement without serious short-term adverse events. Evidence from related immune-mediated diseases suggests that combined blockade of complementary cytokine pathways can enhance efficacy with acceptable safety in selected patients. DTT may represent a promising approach for treatment-resistant HS, warranting further prospective evaluation to understand optimal combinations, safety profiles, and long-term outcomes.