Chan Matthew M K, Kefford Richard F, Carlino Matteo, Clements Arthur, Manolios Nicholas
*The Crown Princess Mary Cancer Centre ∥Rheumatology Department, Westmead Hospital †Melanoma Institute Australia ‡Sydney Medical School, The University of Sydney §Westmead Institute for Cancer Research, Westmead Millennium Institute, Sydney, NSW, Australia.
J Immunother. 2015 Jan;38(1):37-9. doi: 10.1097/CJI.0000000000000060.
We report the acute onset of polyarticular inflammatory arthritis in 2 patients receiving the immune check-point inhibitor, pembrolizumab (MK-3475), anti-PD1 drug for metastatic melanoma after 14 and 11 months therapy, respectively. The first patient had severe tenosynovitis, synovitis, bone marrow edema, and myositis, whereas the second patient had predominantly synovitis and tenosynovitis. Good symptomatic control was obtained with bisphosphonates and salazopyrin, avoiding the use of T-cell immunosuppressants. These cases raise important questions on whether anti-PD1 therapy allows preexisting autoimmune T-cell clones to escape tolerance by suppressing regulatory T cells or whether they allow autoimmunity to develop de novo. These conditions heighten our awareness of complications associated with the clinical use of these agents, and provide a prototypical model for future research into the understanding of autoimmunity.
我们报告了2例接受免疫检查点抑制剂帕博利珠单抗(MK-3475)治疗转移性黑色素瘤的患者分别在治疗14个月和11个月后出现多关节炎性关节炎急性发作。首例患者有严重腱鞘炎、滑膜炎、骨髓水肿和肌炎,而第二例患者主要为滑膜炎和腱鞘炎。使用双膦酸盐和柳氮磺胺吡啶获得了良好的症状控制,避免了使用T细胞免疫抑制剂。这些病例引发了重要问题,即抗PD1疗法是通过抑制调节性T细胞使预先存在的自身免疫性T细胞克隆逃避耐受,还是使自身免疫性疾病从头发生。这些情况提高了我们对这些药物临床使用相关并发症的认识,并为未来研究自身免疫性疾病提供了一个典型模型。