Salzmann Martin, Benesova Karolina, Buder-Bakhaya Kristina, Papamichail Dimitrios, Dimitrakopoulou-Strauss Antonia, Lorenz Hanns-Martin, Enk Alexander H, Hassel Jessica C
Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
Division of Rheumatology, Department of Medicine V, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Cancers (Basel). 2020 Oct 16;12(10):3004. doi: 10.3390/cancers12103004.
BRAF inhibitors (BRAFi), commonly used in BRAF-mutated metastatic melanoma (MM) treatment, frequently cause arthralgia. Although this is one of the most common side effects, it has not been characterized yet.
We retrospectively included all patients treated with BRAFi +/- MEK inhibitors (MEKi) for MM at the National Center for Tumor Diseases (Heidelberg) between 2010 and 2018 and reviewed patient charts for the occurrence and management of arthralgia. The evaluation was supplemented by an analysis of frozen sera.
We included 154 patients (63% males); 31% (48/154) of them reported arthralgia with a median onset of 21 days after the start of the therapy. Arthralgia mostly affected small joints (27/36, 75%) and less frequently large joints (19/36, 53%). The most commonly affected joints were in fingers (19/36, 53%), wrists (16/36, 44%), and knees (12/36, 33%). In 67% (24/36) of the patients, arthralgia occurred with a symmetrical polyarthritis, mainly of small joints, resembling the pattern typically observed in patients affected by rheumatoid arthritis (RA), for which a role of the MAPK signaling pathway was previously described. Patients were negative for antinuclear antibodies, anti-citrullinated protein antibodies, and rheumatoid factor; arthritis was visible in 10 of 13 available PET-CT scans. The development of arthralgia was linked to better progression-free survival and overall survival.
Arthralgia is a common side effect in patients receiving BRAFi +/- MEKi therapy and often presents a clinical pattern similar to that observed in RA patients. Its occurrence was associated with longer-lasting tumor control.
BRAF抑制剂（BRAFi）常用于BRAF突变的转移性黑色素瘤（MM）治疗，常引起关节痛。尽管这是最常见的副作用之一，但尚未得到充分描述。
我们回顾性纳入了2010年至2018年间在德国海德堡国家肿瘤疾病中心接受BRAFi±MEK抑制剂（MEKi）治疗MM的所有患者，并查阅患者病历以了解关节痛的发生情况及处理措施。通过对冻存血清的分析补充评估。
我们纳入了154例患者（63%为男性）；其中31%（48/154）报告有关节痛，中位发病时间为治疗开始后21天。关节痛大多影响小关节（27/36，75%），较少影响大关节（19/36，53%）。最常受累的关节是手指（19/36，53%）、手腕（16/36，44%）和膝盖（12/36，33%）。67%（24/36）的患者关节痛表现为对称性多关节炎，主要累及小关节，类似于类风湿关节炎（RA）患者典型的表现模式，此前已描述过丝裂原活化蛋白激酶（MAPK）信号通路在其中的作用。患者抗核抗体、抗瓜氨酸化蛋白抗体及类风湿因子均为阴性；13份可用的正电子发射断层扫描 - 计算机断层扫描（PET - CT）中有10份可见关节炎表现。关节痛的发生与更好的无进展生存期和总生存期相关。
关节痛是接受BRAFi±MEKi治疗患者的常见副作用，其临床模式常与RA患者相似。其发生与更持久的肿瘤控制相关。
