INTRODUCTION
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with frequent relapses and multisystem involvement, including the joints, kidneys, heart, lungs, central nervous system, and commonly the skin.1 SLE impacts more than 200,000 Americans and 3.4 million worldwide, with a projected global market >$4 billion by 2030.1-4
Cutaneous involvement is a common manifestation of SLE, impacting >80% of patients.1 Cutaneous lupus erythematosus (CLE) comprises acute, subacute, and chronic subtypes, with variable clinical features and risk of progression to SLE.1 Acute CLE presents in a malar or maculopapular pattern, occurring in up to 50% of SLE patients.5 Subacute CLE is a photosensitive annular or papulosquamous eruption observed in 10% to 15% of SLE patients.5 CLE commonly presents as discoid lupus with scaly, erythematous macules or papules that progress to indurated plaques; other chronic CLE manifestations include lupus erythematosus profundus (lupus panniculitis), chilblain lupus erythematosus, and lupus erythematosus tumidus.5,6 Nearly 30% of patients with DLE progress to SLE, and these patients often require systemic therapy.5,6 Notably, there are no US Food and Drug Administration (FDA)-approved therapies for CLE, highlighting a substantial therapeutic unmet need.
Treatment of SLE relies on immunosuppression to prevent flares and modulate systemic involvement.1 Hydroxychloroquine (HCQ) is a systemic therapy for CLE and SLE.1 However, HCQ can be associated with adverse events (AEs), including cardio- toxicity, neuromyotoxicity, hyperpigmentation, and vision loss.7 HCQ use may yield incomplete response (~50%) and flares.6 Given toxicity and efficacy concerns, there remains a clear need for safer, more effective SLE therapies.
The pathophysiology of SLE is multifactorial, with dysregulated B- and T-cells central to disease pathogenesis and key therapeutic targets.8 B-cell dysregulation drives disease through loss of tolerance to self-antigens, generating pathogenic auto- antibodies, immune complex deposition, complement activation, and multiorgan damage.1 Reduced B-cell receptor signaling, including impaired tolerance and lowered activation thresholds, promotes abnormal stimulation of autodoi
Cutaneous involvement is a common manifestation of SLE, impacting >80% of patients.1 Cutaneous lupus erythematosus (CLE) comprises acute, subacute, and chronic subtypes, with variable clinical features and risk of progression to SLE.1 Acute CLE presents in a malar or maculopapular pattern, occurring in up to 50% of SLE patients.5 Subacute CLE is a photosensitive annular or papulosquamous eruption observed in 10% to 15% of SLE patients.5 CLE commonly presents as discoid lupus with scaly, erythematous macules or papules that progress to indurated plaques; other chronic CLE manifestations include lupus erythematosus profundus (lupus panniculitis), chilblain lupus erythematosus, and lupus erythematosus tumidus.5,6 Nearly 30% of patients with DLE progress to SLE, and these patients often require systemic therapy.5,6 Notably, there are no US Food and Drug Administration (FDA)-approved therapies for CLE, highlighting a substantial therapeutic unmet need.
Treatment of SLE relies on immunosuppression to prevent flares and modulate systemic involvement.1 Hydroxychloroquine (HCQ) is a systemic therapy for CLE and SLE.1 However, HCQ can be associated with adverse events (AEs), including cardio- toxicity, neuromyotoxicity, hyperpigmentation, and vision loss.7 HCQ use may yield incomplete response (~50%) and flares.6 Given toxicity and efficacy concerns, there remains a clear need for safer, more effective SLE therapies.
The pathophysiology of SLE is multifactorial, with dysregulated B- and T-cells central to disease pathogenesis and key therapeutic targets.8 B-cell dysregulation drives disease through loss of tolerance to self-antigens, generating pathogenic auto- antibodies, immune complex deposition, complement activation, and multiorgan damage.1 Reduced B-cell receptor signaling, including impaired tolerance and lowered activation thresholds, promotes abnormal stimulation of autodoi
