B細胞去除療法在全身性紅斑狼瘡的歷史與新局

The Evolution and Future of B-cell Depleting Therapies in Systemic Lupus Erythematosus

B細胞在紅斑性狼瘡中扮演關鍵的致病角色。自2000年起，B細胞療法逐漸成為研究焦點。早期以抗CD20單株抗體rituximab為代表，雖在臨床個案顯示療效，但大型試驗未達主要終點。相對地，針對BAFF（B-cell activating factor）的belimumab在2011年成為首個獲FDA核准的SLE生物製劑。此後，CD22抑制劑、BTK抑制劑等藥物陸續投入研究，然而直到近5年才有2個新藥-第二代anti-CD20（obinutuzumab）與anti-CD40L（dapirolizumab）的3期試驗達標，顯示紅斑狼瘡新藥臨床試驗不易成功的本質。此外，針對漿細胞的抑制策略（如anti-CD38）亦有治療的潛力。近年來，CAR-T與T cell engager（TCE）等創新療法更被引進，帶來具有「重塑免疫」可能的劃時代進展。臨床實務上，已核可使用的belimumab為現今紅斑治療的重要藥物、而rituximab則常作為後線療法的選擇。綜觀而言，B細胞療法在紅斑狼瘡的發展歷經挫折與突破，隨著新藥與新技術出現，為病人提供更多元且精準的治療選擇。

B cells play a pivotal pathogenic role in systemic lupus erythematosus (SLE). Since 2000, B-cell–targeted therapies have gradually become a major research focus. The earliest approach, exemplified by the anti-CD20 monoclonal antibody rituximab, demonstrated clinical efficacy in case series, but large randomized trials failed to meet primary endpoints. In contrast, the anti-BAFF agent belimumab became the first FDA-approved biologic for SLE in 2011. Subsequently, agents such as CD22 inhibitors and BTK inhibitors were investigated, yet only in the past five years have two novel agents—anti-CD20 obinutuzumab and anti-CD40L dapirolizumab—achieved positive phase 3 trial results, underscoring the challenges of lupus drug development. Strategies targeting plasma cells (e.g., anti-CD38) and small molecules such as JAK inhibitors have also shown promise. More recently, innovative therapies including CAR-T cells and T cell engagers (TCEs) have been introduced, offering the potential for immune reprogramming and representing groundbreaking advances. In clinical practice, belimumab is now established as a key therapeutic option for SLE, while rituximab remains an off-label, later-line therapy. Overall, B-cell–targeted therapy in SLE has experienced setbacks and breakthroughs, and with the advent of new agents and technologies, patients now have access to more diverse and precise treatment choices.