重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合沙利度胺、柳氮磺胺吡啶治疗强直性脊柱炎髋关节病变的临床研究

摘要

Objective To observe the efficacy and safety of rhTNFR-IgG fusion protein in combination with thalidomide and sulfasalazine for hip involvement of ankylosing spondylitis (AS). Methods 36 AS patients with hip involvement were treated with rhTNFR-IgG fusion protein 50mg once weekly for 12 weeks,in combination with DMARDS(thalidomide 100mg once a day,and sulfasalazine 1.0g twice a day ),after the initial 12 weeks,maintaining the DMARDS therapy following discontinuation of rhTNFR-IgG fusion protein until 36 weeks.The outcome,including symptoms,signs,erythrocyte sedimentation rate (ESR),c-reactive protein (CRP),Bath AS disease activity index (BASDAI),magnetic resonance imaging (MRI) for hip bone marrow edema and side effects,were recorded. Results 36 week-treatment of rhTNFR-IgG fusion protein in combination with thalidomide and sulfasalazine can significantly improve BASDAI(6.13±1.05) before treatment vs(3.14±0.36 )at 36 weeks after treatmeng(P<0.05).Other measures such as stiffness in the morning,pain at night,ESR and CRP also improved significantly(P < 0.05).Hip bone marrow edema in MRI receded.Besides,we found while maintaining the DMARDS therapy for 24 weeks after discontinuation of rhTNFR-IgG fusion protein,the symptom,sign,inflammation marks(ESR and CRP),BASDAI and hip bone marrow edema were not worsen compared with them at 12 weeks when rhTNFR-IgG fusion protein was just finished(P>0.05).The most common side effects were reaction in injection site and minimally abnormal liver function. Conclusion rhTNFR-IgG fusion protein in combination with thalidomide and sulfasalazine for hip involvement of AS are highly effective and well tolerated.%目的：观察重组人II型肿瘤坏死因子受体-抗体融合蛋白联合沙利度胺、柳氮磺胺吡啶治疗强直性脊柱炎髋关节病变的临床疗效和安全性。方法应用重组人II型肿瘤坏死因子受体-抗体融合蛋白治疗36例AS髋关节病变的患者，50mg/次，每周1次，疗程12周，同时加用DMARDS（沙利度胺100mg，1次/晚，柳氮磺胺吡啶1.0g/次，2次/日），12周后停用重组人II型肿瘤坏死因子受体-抗体融合蛋白，继续DMARDS至36周。观察治疗前后患者的症状、体征、红细胞沉降率（ESR）、C反应蛋白（CRP）、AS疾病活动指数（BASDAI）、髋部骨髓水肿MRI等指标及不良反应。结果重组人II型肿瘤坏死因子受体-抗体融合蛋白联合沙利度胺、柳氮磺胺吡啶治疗强直性脊柱炎36周后可以显著改善BASDAI，治疗前BASDAI平均评分（6.13±1.05）分，治疗36周后BASDAI平均评分（3.14±0.36）分，差异具有统计学意义（P＜0.05），晨僵、夜间痛、ESR、CRP等疗效指标治疗前后差异具有统计学意义（P＜0.05）。MRI显示治疗后髋关节骨髓水肿显著改善。另外，本研究发现在停用重组人II型肿瘤坏死因子受体-抗体融合蛋白、继续使用沙利度胺、柳氮磺胺吡啶24周后(36周时)，患者的临床症状、体征、炎性指标（ESR、CRP）、BASDAI和骨髓水肿等较重组人II型肿瘤坏死因子受体-抗体融合蛋白治疗12周时差异无统计学意义（P＞0.05）。最常见的不良反应主要是注射部位反应和轻度肝功能损害。结论重组人II型肿瘤坏死因子受体-抗体融合蛋白联合沙利度胺、柳氮磺胺吡啶治疗强直性脊柱炎髋关节病变疗效显著，患者耐受性好。