Improvement of skin manifestations of refractory connective tissue diseases by T-cell engager treatment

Background: The skin is a central organ involved in systemic autoimmune diseases (AID). Next to T-cell activation, the formation of pathogenic B-cells and plasma cells as well as the emergence of autoantibodies is a crucial process in AID. While some patients with AID can be managed well by conventional immunosuppressants, others develop highly-treatment resistant disease and require new therapeutic concepts that tackle pathologic B-cell and plasma cell activation. T-cell engagers are a powerful therapeutic tool to deplete B-cell and plasma cells and may be efficacious to improve skin manifestations of systemic AID.

Methods: We evaluated the effect of the BCMA-directed T-cell engager teclistamab on cutaneous manifestations of highly treatment-resistant systemic AID. Skin activity was assessed using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), and skin-related quality of life using the Dermatology Life Quality Index (DLQI), based on clinical findings and patient interviews before and after treatment.

Results: Three patients (two with dermatomyositis, one with systemic sclerosis) with treatment-resistant disease and cutaneous manifestations were treated with teclistamab. In both dermatomyositis patients, skin disease activity substantially decreased, and skin-related quality of life improved. In the patient with systemic sclerosis, digital ulcers resolved, skin fibrosis decreased, hair regrew and the skin-related quality of life normalized.

Conclusion: In this small case series, BCMA-directed T-cell engager therapy was associated with improvement of skin manifestations and skin-related quality of life in patients with highly treatment-refractory AID. Larger studies are required to systematically assess efficacy, safety, and durability of cutaneous responses to T-cell engagers.