Effect of Dosage Optimization of Recombinant Human Tumor Necrosis Factor Receptor-Fc Fusion Protein for Injection on Patients with Ankylosing Spondylitis and Hip Joint Disease

doi:10.12114/j.issn.1007-9572.2019.00.112

Abstract

Abstract: Background　The high cost and obvious adverse reactions in long-term use of biological agents in patients with ankylosing spondylitis and hip joint disease are not conducive to improving treatment compliance；it is worth discussing how to solve related problems by reducing the dose.Objective　To investigate the influence of dosage optimization of recombinant human tumor necrosis factor receptor-Fc fusion protein（rhTNFR∶Fc） on severity of symptoms，laboratory indicators and safety of patients with ankylosing spondylitis and hip joint disease.Methods　A total of 136 patients with ankylosing spondylitis accompanied by hip joint lesions were divided into control group（n=68） and experimental group（n=68） according to the visit order.The routine dose and optimal dose of rhTNFR∶Fc were used respectively.The clinical remission rate，symptom severity index，imaging index，laboratory index and incidence of adverse drug reactions before and after treatment were compared between the two groups at the 24th week after treatment.Results　There were no significant differences in Assessment in Ankylosing Spondylitis（ASAS） 20，ASAS 40 and partial remission of ASAS between the two groups（P>0.05）.At the 24th week after treatment，the Ankylosing Spondylitis Disease Activity Score（ASDAS），Bath Ankylosing Spondylitis Disease Activity Index（BASDAI），Bath Ankylosing Spondylitis Function Index（BASFI），pain visual analogue score（VAS pain score），hip function score（Harris score），Spondyloarthritis Research Consortium of Canada（SPARCC） MR score，erythrocyte sedimentation rate（ESR） and C-reactive protein level were significantly better than those before treatment（P<0.05），and there was no significant difference in X-ray score of sacroiliac joint（P>0.05）；There was no significant difference in indicators between the two groups（P>0.05）.At the 24th week after treatment，the incidence of adverse drug reactions in the experimental group was lower than that in the control group（P<0.05）.Conclusion　The dosage optimization scheme of rhTNFR∶Fc has similar clinical efficacy with the conventional dosage scheme for patients with ankylosing spondylitis and hip joint lesions，but it is more conducive to reducing the risk of adverse reactions with better treatment safety.

Key words: Spondylitis, ankylosing；Osteoarthritis, Hip；Dose-response relationship, drug；rhTNFR∶Fc；Etanercept analogues

摘要： 背景　强直性脊柱炎伴髋关节病变患者长期足量使用生物制剂所产生的高昂费用和明显不良反应不利于改善治疗依从性，通过降低给药剂量解决相关问题值得探讨。目的　探讨注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白剂量优化方案对强直性脊柱炎伴髋关节病变患者症状严重程度、实验室指标及安全性的影响。方法　选择四川省达州市中心医院2016年1月—2018年1月收治的强直性脊柱炎伴髋关节病变患者共136例，按就诊顺序分为对照组（n=68）和试验组（n=68），分别采用注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白常规剂量和优化剂量治疗。比较治疗后24周两组患者临床缓解率、治疗前及治疗后24周症状严重程度指标、影像学指标、实验室指标及药物不良反应发生率。结果　两组强直性脊柱炎的总体评价（ASAS）的ASAS20、ASAS40及ASAS部分缓解率比较，差异无统计学意义（P>0.05）。治疗后24周，两组强直性脊柱炎疾病活动（ASDAS）评分、Bath强直性脊柱炎疾病活动性指数（BASDAI）、Bath强直性脊柱炎功能指数（BASFI）、疼痛视觉模拟（VAS）评分、髋关节功能（Harris）评分、加拿大脊柱骨关节研究协会（SPARCC）MR评分、红细胞沉降率（ESR）及C反应蛋白水平均优于治疗前，差异有统计学意义（P<0.05），骶髂关节X线评分比较差异无统计学意义（P>0.05）；两组以上指标水平组间比较，差异无统计学意义（P>0.05）。治疗后24周，试验组药物不良反应发生率低于对照组，差异有统计学意义（P<0.05）。结论　注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白剂量优化方案用于强直性脊柱炎伴髋关节病变患者与常规剂量方案具有相近临床疗效，但更有助于降低不良反应发生风险，治疗安全性更佳。

关键词: 脊柱炎, 强直性；骨关节炎, 髋；剂量效应关系, 药物；注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白；依那西普类似物

ZHANG Weihua,WANG Tingting,WANG Dongmei, et al. Effect of Dosage Optimization of Recombinant Human Tumor Necrosis Factor Receptor-Fc Fusion Protein for Injection on Patients with Ankylosing Spondylitis and Hip Joint Disease　[J]. Chinese General Practice, 2019, 22(16): 1973-1977. DOI: 10.12114/j.issn.1007-9572.2019.00.112.
张卫华,王婷婷,王东梅等. 注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白剂量优化方案对强直性脊柱炎伴髋关节病变患者的影响[J]. 中国全科医学, 2019, 22(16): 1973-1977. DOI: 10.12114/j.issn.1007-9572.2019.00.112.

References

［1］CHEN J，LIN S，LIU C．Sulfasalazine for ankylosing spondylitis［J］．Cochrane Database Syst Rev，2014（11）：CD004800．DOI：10.1002/14651858.CD004800.pub3.
［2］KANTERS T A，STEVANOVIC J，HUYS I，et al．Adoption of biosimilar infliximab for rheumatoid arthritis，ankylosing spondylitis，and inflammatory bowel diseases in the EU5：a budget impact analysis using a Delphi panel［J］．Front Pharmacol，2017，8（5）：322-327．DOI：10.3389/fphar.2017.00322.
［3］MONTI S，TODOERTI M，CODULLO V，et al．Prevalence of Ankylosing Spondylitis Disease Activity Score（ASDAS） inactive disease in a cohort of patients treated with TNF-alpha inhibitors［J］．Mod Rheumatol，2018，28（3）：542-549．DOI：10.1080/14397595.2017.1367076.
［4］IBá?EZ VODNIZZA S，VISMAN I M，VAN D C，et al．Muscle wasting in male TNF-α blocker na?ve ankylosing spondylitis patients：a comparison of gender differences in body composition［J］．Rheumatology（Oxford），2017，56（9）：1566-1572．DOI：10.1093/rheumatology/kex187.
［5］梅西埃，戴闽，姚浩群．实用骨科学精要［M］．北京：人民军医出版社，2016：213-214.
［6］依那西普治疗类风湿关节炎和强直性脊柱炎专家组．依那西普治疗类风湿关节炎和强直性脊柱炎的专家建议（2013）［J］．中华医学杂志，2013，93（18）：1363-1369．DOI：10.3760/cma.j.issn.0376-2491.2013.18.002.
Expert Group on Enacept in the Treatment of Rheumatoid Arthritis and Ankylosing Spondylitis．Expert recommendations for Enacept in the treatment of rheumatoid arthritis and ankylosing spondylitis（2013）［J］．National Medical Journal of China，2013，93（18）：1363-1369．DOI：10.3760/cma.j.issn.0376-2491.2013.18.002.
［7］MOLNAR C，SCHERER A，BARALIAKOS X，et al．TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity：results from the Swiss Clinical Quality Management Cohort［J］．Ann Rheum Dis，2018，77（1）：63-69．DOI：10.1136/annrheumdis-2017-211544.
［8］ALMIRALL M，GIMENO R，SALMAN-MONTE T C，et al．Drug levels，immunogenicity and assessment of active sacreiliitis in patients with axial spondyloarthritis under biologic mpefing strategy［J］．Rheumatol Int，2016，36（4）：575-578．DOI：10.1007/s00296-016-3428-0.
［9］LIU J，WANG X，HAN Z，et al．Dose reduction of recombinant human tumor necrosis factor inhibitors（Etanercept）con be effective in ankylosing spondylitis patients with synovitis of the hip in a Chinese population［J］．Int J Immunopathol Pharmacol，2016，29（3）：510-515．DOI：10.1177/0394632016656013.
［10］UGAN Y，NAZIROGLU M，SAHIN M，et al．Anti-tumor necrosis factor alpha（Infliximab）attenuates apoptosis，oxidative stress，and calcium ion entry through modulation of cation channels in neutrophils of patients with ankylosing spondylitis［J］．J Membr Biol，2016，249（4）：437-447．DOI：10.1007/s00232-016-9884-3.
［11］JEONG H，EUN Y H，KIM I Y，et al．Effect of tumor necrosis factor α inhibitors on spinal radiographic progression in patients with ankylosing spondylitis［J］．Int J Rheum Dis，2018，21（5）：1098-1105．DOI：10.1111/1756-185X.13270.
［12］CARBO M J G，SPOORENBERG A，MAAS F，et al．Ankylosing spondylitis disease activity score is related to NSAID use，especially in patients treated with TNF-α inhibitors［J］．PLoS One，2018，13（4）：e0196281．DOI：10.1371/journal.pone.0196281.
［13］PSARELIS S，HAJINEOCLI A P D，HADJICOSTA E，et al．Is secukinumab a safe alternative treatment for ankylosing spondylitis with Guillain Barré syndrome after anti-TNF-α treatment? Case report and literature review［J］．Clin Rheumatol，2017，36（5）：1197-1199．DOI：10.1007/s10067-017-3573-1.
［14］KARATAS G，BAL A，YUCEEGE M，et al．Evaluation of sleep quality in patients with ankylosing spondylitis and efficacy of anti-TNF-α therapy on sleep problems：a polisomnographic study［J］．Int J Rheum Dis，2018，21（6）：1263-1269．DOI：10.1111/1756-185X.13102.
［15］KIM M，WON J Y，CHOI S Y，et al．Anti-TNFα treatment for HLA-B27 positive ankylosing spondylitis-related uveitis［J］．Am J Ophthalmol，2016，170（10）：32-40．DOI：10.1016/j.ajo.2016.07.016.
［16］MAAS F，ARENDS S，BROUWER E，et al．Reduction in spinal radiographic progression in ankylosing spondylitis patients receiving prolonged treatment with TNF-α inhibitors［J］．Arthritis Care Res（Hoboken），2017，69（7）：1011-1019．DOI：10.1002/acr.23097.

[1]	WANG Xiangbin, LONG Yubin, WANG Chong, LI Yong, MAIWULAN· Mansuerjiang, TIAN Zheng, AIKEBAIER· Younusi. Application of Unilateral Biportal Endoscopy Technique in the Treatment of Lumbar Brucellosis Spondylitis [J]. Chinese General Practice, 2023, 26(08): 963-971.
[2]	LI Dongxia，CHEN Yingying，HAN Mei，TAO Qingwen. Clinical Characteristics and Influencing Factors of Ankylosing Spondylitis with Hypo-high-density Lipoproteinemia　 [J]. Chinese General Practice, 2019, 22(20): 2422-2425.