生物制剂治疗强直性脊柱炎的长期疗效观察

Long-term effect of biological anti-rheumatic drugs on ankylosing spondylitis

目的观察应用生物制剂改善病情抗风湿药(bDMARDs)对AS患者的长期疗效与药物相关不良反应情况,为临床诊疗提供参考。方法收集北京大学深圳医院风湿免疫科有至少5年完整病历记录的AS患者,选取其中全程单用bDMARDs或同时联合传统抗风湿药并且连续治疗时间至少3年的为治疗组,未治疗或治疗时间低于3个月的为对照组。收集所有患者用药情况,对5年病程前后的临床症状、炎症指标、影像学结果、用药过程出现的药物相关不良反应等数据进行统计学分析。计数资料进行χ^(2)检验,符合正态分布的计量资料采用t检验,治疗前后对照应用配对t检验进行统计学处理。结果共纳入符合条件患者114例,治疗组64例,对照组50例。随访时间、初次就诊的主诉病程、年龄、性别比、HLA-B27阳性率、晨僵时间、夜间痛、外周关节炎、ESR、CRP、影像学表现等基线资料对比差异无统计学意义。5年后,治疗组较对照组的晨僵时间更短[(3±7)min与(26±37)min,t=4.827,P<0.01],夜间痛比例更低[(3/64,4.8%)与(29/50,58.0%),χ^(2)=38.329,P<0.01],ESR更低[(14±14)mm/1 h与(20±18)mm/1 h,t=2.102,P=0.038],CRP更低[(7±8)mg/L与(14±19)mg/L,t=2.431,P=0.017],骶髂关节炎进展比例更低[(18/64,28.1%)与(35/50,70.0%),χ^(2)=19.786,P<0.01]。药物相关不良反应主要有:可逆转的白细胞减少、转氨酶升高、注射部位红肿。结论未治疗的AS患者5年以后骶髂关节影像学进展达70%,连续3年以上生物制剂治疗可长期有效控制大部分AS患者的临床症状、降低炎症指标、延缓骶髂关节影像进展。

Objective To study the efficacy and drug-related adverse reactions of long-term appli-cation of biological anti-rheumatic drugs(bDMARDs)to patients with ankylosing spondylitis(AS),and provide reference for clinical diagnosis and treatment.Methods We retrospectively analyzed the clinical data of AS patients who were followed-up for more than 5 years in the Department of Rheumatology and Immunology of Peking University Shenzhen Hospital.The patients treated with bDMARDs alone or combined with traditional antirheumatic drugs were included as the treatment group,while those who did not receive biological or non-biological antirheumatic therapy were included as the control group.The data collected included clinical sym-ptoms,inflammatory biomarkers,imaging results,drug applications and drug-related adverse reactions,etc.The counting data were tested byχ^(2) test,the measurement data in normal distribution was tested by t test,and the measurement data that not normally distributed was tested by Mann-Whitney U test.Paired test was used for statistical processing before and after treatment.Results We collected the data of 114 eligible patients,including 64 in the treatment group and 50 in the control group.There were no significant differences in baseline data between the 2 groups,including mean follow-up time,course of disease,age,sex ratio,HLA-B27 positive rate,morning stiffness duration,night pain,peripheral arthritis,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),and imaging.After 5 years,patients in the treatment group had shorter morning stiffness[(3±7)min vs(26±37)min,t=4.827,P<0.01],lower nighttime pain rates[(3/64,4.8%)vs(29/50,58.0%),χ^(2)=38.329,P<0.01],lower ESR level[(14±14)mm/1 h vs(20±18)mm/1 h,t=2.102,P=0.038],lower CRP level[(7±8)mg/L vs(14±19)mg/L,t=2.431,P=0.017],and lower progression rate of sacroiliac arthritis[(18/64,28.1%)vs(35/50,70.0%),χ^(2)=19.786,P<0.01],than the control group.The main drug-related adverse reactions in the treatment groupincluded reversible leucopenia,elevated transaminase level,redness and swelling at the injection site.Conclusion Biologics treatment for more than 3 consecutive years can effectively control the clinical symptoms of most AS patients,reduce inflammatory indicators and delay the imaging progression of the sacroiliac joint.Without treatment,the imaging progress of the sacroiliac joint in AS patients could be 70%after 5 years.