Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, Barcelona, Spain.
Department of Rheumatology, Hospital Privado Centro Médico de Córdoba, Córdoba. Argentina.
Autoimmun Rev. 2019 Mar;18(3):262-269. doi: 10.1016/j.autrev.2018.10.006. Epub 2019 Jan 11.
To analyze the effectiveness and safety of rituximab (RTX) for the treatment of refractory systemic sclerosis (SSc)-associated calcinosis.
We undertook an observational study of patients with this complication treated with 1 or more cycles of RTX (1 g × 2 weeks) and evaluated for at least 12 months after RTX treatment in a single center. The primary outcome measures of the study were the improvement of calcinosis symptoms (pain, signs of local inflammation, and new episodes of skin ulceration) and the radiologic evolution of the calcification(s).
We treated 8 patients with refractory SSc-related calcinosis with RTX (off-label use). The main indications for RTX were complicated calcinosis unresponsive to previous therapies with concomitant arthritis in 2 patients and refractory arthritis or interstitial lung fibrosing disease in the remaining 6 patients. The mean number of RTX cycles administered was 3.12 ± 2.1 (range, 1-7), the median duration of RTX treatment was 9 months (interquartile range [IQR], 7.5-36 months), and the median follow-up after the first infusion of RTX dose was 19 months (IQR, http://catsalut.gencat.cat/web/.content/minisite/catsalut/proveidors_professionals/medicaments_farmacia/phf_mhda/informes_camse/esclerosi_sistemica/Dictamen-CAMS_-ES_-web.pdf (n.d.) 5-45 months). Four patients (50%) had a significant improvement in clinical symptoms (sustained improvement in the visual analog scale for pain of at least 50% and no new episodes of local inflammation or skin ulceration). Two of these patients (25%) also had a complete resolution or significant reduction in the size of the calcification(s) on X-ray, according with the radiographical scoring system for calcinosis developed by the Scleroderma Clinical Trials Consortium. In the remaining 4 patients (50%), RTX did not provide any significant clinical or radiologic benefit for calcinosis. The frequency of adverse effects was low, occurring in only 1 patient (12.5%), who developed upper respiratory tract infections not requiring hospitalization.
Our preliminary data suggest that RTX may be helpful as a rescue therapy in selected cases of severe and refractory SSc-related calcinosis.
分析利妥昔单抗（RTX）治疗难治性系统性硬化症（SSc）相关钙化的疗效和安全性。
我们对在单中心接受 1 或多个 RTX 周期（1g×2 周）治疗的此类并发症患者进行了观察性研究，并在 RTX 治疗后至少 12 个月进行评估。研究的主要终点为钙化症状（疼痛、局部炎症迹象和新的皮肤溃疡发作）改善和钙化的影像学进展。
我们用 RTX 治疗了 8 例难治性 SSc 相关钙化患者（超适应证使用）。RTX 的主要适应证是 2 例伴有关节炎的复杂钙化对先前治疗无反应，以及其余 6 例难治性关节炎或间质性肺纤维化疾病。接受的 RTX 周期数平均为 3.12±2.1（范围，1-7），RTX 治疗的中位持续时间为 9 个月（四分位距 [IQR]，7.5-36 个月），RTX 剂量首次输注后的中位随访时间为 19 个月（IQR，http://catsalut.gencat.cat/web/.content/minisite/catsalut/proveidors_professionals/medicaments_farmacia/phf_mhda/informes_camse/esclerosi_sistemica/Dictamen-CAMS_-ES_-web.pdf（n.d.）5-45 个月）。4 例患者（50%）临床症状有明显改善（疼痛视觉模拟评分至少改善 50%，且无新的局部炎症或皮肤溃疡发作）。这 2 例患者（25%）的 X 线钙化也完全消退或大小明显缩小，符合 Scleroderma Clinical Trials Consortium 制定的钙化影像学评分系统。在其余 4 例患者（50%）中，RTX 对钙化无明显的临床或影像学益处。不良反应频率较低，仅 1 例患者（12.5%）发生上呼吸道感染，无需住院。
我们的初步数据表明，RTX 可能有助于治疗严重和难治性 SSc 相关钙化的选定病例。
