目的: 观察单用一种改善病情抗风湿药托法替布治疗老年难治性类风湿关节炎(rheumatoid arthritis,RA)的临床疗效及安全性。方法: 选择15例老年难治性(传统慢作用药和/或生物制剂类疗效欠佳)RA(D2T-RA)患者,以托法替布治疗。记录患者一般资料,分析用药前(基线时)及用药后2、4、8、12 w相关病情评估指标,包括关节肿胀数(SJC),关节压痛数(TJC),红细胞沉降率(ESR),C-反应蛋白(CRP),DAS28评分,简化、临床疾病活动指数(SDAI、CDAI)和类风湿因子(RF)以及不良反应的发生情况。结果: 治疗2 w后,老年D2T-RA患者CRP、DAS28评分,CDAI、SDAI与治疗前相比差异有统计学意义(P<0.05);治疗4、8、12 w后,患者ESR、CRP、DAS28评分,CDAI、SDAI、SJC、TJC与治疗前相比差异有统计学意义(P<0.05);治疗4 w与治疗2 w,治疗8 w与治疗4 w相比,患者ESR、CRP、DAS28评分,CDAI、SDAI差异均有统计学意义(P<0.05);治疗12 w与治疗8 w相比,患者CRP、DAS28评分,CDAI、SDAI差异有统计学意义(P<0.05)。结论: 托法替布治疗D2T-RA临床疗效显著,同时需密切关注其长期疗效和不良反应的发生。 |
Objective: To observe the clinical efficacy and safety of tofacitinib in the treatment of refractory rheumatoid arthritis(RA) in the elderly. Methods: A total of 15 elderly patients with refractory RA(D2T-RA) who had poor curative effect on traditional anti-rheumatic drugs(DMARDs) and/or biologics were observed and treated with tofacitinib monotherapy. General data of the patients were recorded. Relevant disease assessment indicators including joint swelling number(SJC), joint tenderness number(TJC), erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), DAS28 score, simplified/clinical disease activity index(SDAI/CDAI), and rheumatoid factor(RF) were observed before medication(baseline)and after medication at 2 w, 4 w, 8 w, and 12 w, and the occurrence of adverse reactions. Results: After 2 weeks of treatment, there were significant differences of CRP, DAS28 score, CDAI and SDAI in elderly patients with D2T-RA compared with before treatment(P<0.05). After treatment of 4 w, 8 w and 12 w, the ESR, CRP, DAS28 scores, CDAI, SDAI, SJC, TJC and TJC were significantly different from those before treatment(P<0.05). Compared 4 w treatment with 2 w treatment as well as 8 w treatment with 4 w treatment, ESR, CRP, DAS28 scores, CDAI and SDAI were significantly different(P<0.05). Compared with 12 w treatment with 8 w treatment, the CRP and DAS28 scores, CDAI and SDAI were significantly different(P<0.05). Conclusion: Tofacitinib has a significant clinical effect in the treatment of D2T-RA, and it is necessary to pay close attention to its long-term efficacy and the occurrence of adverse reactions. |
[1] JIN S,LI M,FANG Y,et al.Chinese registry of rheumatoid arthritis(CREDIT):Ⅱ.prevalence and risk factors of major comorbidities in Chinese patients with rheumatoid arthritis[J].Arthritis Res Ther,2017,19(1):251.
[2] 李宏超,徐丽玲,苏茵.难治性类风湿关节炎诊治探讨[J].中华风湿病学杂志,2019(10):689-693.
[3] JAMMAL T E,GERFAUD-VALENTIN M,SōVE P,et al.Inhibition of JAK/STAT signaling in rheumatologic disorders:the expanding spectrum[J].Joint Bone Spine,2020,87(2):119-129.
[4] BURMESTER G R,BLANCO R,CHARLES-SCHOEMAN C,et al.ORAL step investigators.Tofacitinib(CP-690,550)in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors:a randomised phase 3 trial[J].Lancet,2013,381(9865):451-460.
[5] KREMER J,LI Z G,HALL S,et al.Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis:a randomized trial[J].Ann Intern Med,2013,159(4):253-261.
[6] ZHU H,LI R,DA Z,et al.Remission assessment of rheumatoid arthritis in daily practice in China:a cross-sectional observational study[J].Clin Rheumatol,2018,37(3):597-605.
[7] ROODENRIJS N M T,VAN DER GOES M C,WELASING P M J,et al.Difficult-to-treat rheumatoid arthritis:contributing factors and burden of disease[J].Rheumatology(Oxford),2021,60(8):3778-3788.
[8] BÉCōDE M,ALASTI F,GESSL I,et al.Risk profiling for a refractory course of rheumatoid arthritis[J].Semin Arthritis Rheum,2019,49(2):211-217.
[9] DI SANTE G,TOLUSSO B,FEDELE A L,et al.Collagen specific T-cell repertoire and HLA-DR alleles:biomarkers of active refractory rheumatoid arthritis[J].EBio Medicine,2015,2(12):2037-2045.
[10] ZHENG N,GUO C,WU R.Iguratimod is effective in refractory rheumatoid arthritis patients with inadequate response to methotrexate-cyclosporin a-hydroxychloroquine-prednisone[J].Scand J Rheumatol,2018,47(5):422-424.
[11] 安燕,张雪,薛一萍.免疫净化治疗难治性类风湿性关节炎的有效性研究[J].中国现代医生,2021,59(14):56-58.
[12] KARONITSCH T,BECKMANN D,DALWIGK K,et al.Targeted inhibition of Janus kinases abates interfon gamma-induced invasive behaviour of fibroblast-like synoviocytes[J].Rheumatology(Oxford),2018,57(3):572-577.
[13] ÁLVARO-GRACIA J M,GARCIA-LLORENTE J F,VALDERRAA M,et al.Update on the safety profile of tofacitinib in rheumatoid arthritis from clinical trials to real-world studies:anarrative review[J].Rheumatol Ther,2021,8(1):17-40.
[14] LEE E B,FLEISCHMANN R,HALL S,et al.ORAL start investigators.Tofacitinib versus methotrexate in rheumatoid arthritis[J].N Engl J Med,2014,370(25):2377-2386.
[15] FLEISCHMANN R,MYSLER E,HALL S,et al.Efficacy and safety of tofacitinib monotherapy,tofacitinib with methotrexate,and adalimumab with methotrexate in patients with rheumatoid arthritis(ORAL Strategy):a phase 3b/4,double-blind,head-to-head,randomised controlled trial[J].Lancet,2017,390(10093):457-468.
[16] LEE Y H,SONG G G.Comparative efficacy and safety of tofacitinib,baricitinib,upadacitinib,and filgotinib in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs[J].Z Rheumatol,2021,80(4):379-392.
[17] MORI S,YOSHITAMA T,UEKI Y.Tofacitinib therapy for rheumatoid arthritis:a direct comparison study between biologic-naïve and experienced patients[J].Intern Med,2018,57(5):663-670.
[18] LI Z,AN Y,SU H,et al.Tofacitinib with conventional synthetic disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis:patient-reported outcomes from a Phase 3 randomized controlled trial[J].Int J Rheum Dis,2018,21(2):402-414.
[19] LI Z G,LIU Y,XU H J,et al.Efficacy and safety of tofacitinib in Chinese patients with rheumatoid arthritis[J].Chin Med J,2018,131(22):2683-2692.
[20] NAKAYAMADA S,KUBO S,IWATA S,et al.Recent progress in JAK inhibitors for the treatment of rheumatoid arthritis[J].Bio Drugs,2016,30(5):407-419. |
