Email Alert | RSS

北京大学学报（医学版） ›› 2023, Vol. 55 ›› Issue (6): 1013-1021. doi: 10.19723/j.issn.1671-167X.2023.06.009

• 论著 • 上一篇    下一篇

艾拉莫德联合托法替布治疗难治性中重度类风湿关节炎的疗效

邹雪1,2,白小娟1,张丽卿1,*()   

  1. 1. 山西医科大学附属汾阳医院, 山西省汾阳医院风湿免疫科, 山西汾阳 032200
    2. 苏州永鼎医院消化内科, 江苏苏州 215100
  • 收稿日期:2023-08-24 出版日期:2023-12-18 发布日期:2023-12-11
  • 通讯作者: 张丽卿 E-mail:zhanglq828@sohu.com
  • 基金资助:
    山西省汾阳医院科技攻关重点项目(2021-2022-03)

Effectiveness of tofacitinib combined with iguratimod in the treatment of difficult-to-treat moderate-to-severe rheumatoid arthritis

Xue ZOU1,2,Xiao-juan BAI1,Li-qing ZHANG1,*()   

  1. 1. Department of Rheumatology and Immunology, Fenyang Hospital Affiliated to Shanxi Medical University, Shanxi Province Fenyang Hospital, Fenyang 032200, Shanxi, China
    2. Department of Gastroenterology, Suzhou Yongding Hospital, Suzhou 215100, Jiangsu, China
  • Received:2023-08-24 Online:2023-12-18 Published:2023-12-11
  • Contact: Li-qing ZHANG E-mail:zhanglq828@sohu.com
  • Supported by:
    the Key Science and Technology Program of Shanxi Province Fenyang Hospital(2021-2022-03)

RICH HTML

   

PDF (PC)

摘要：

目的: 探讨艾拉莫德联合托法替布在难治性中重度类风湿关节炎(rheumatoid arthritis, RA)患者中的疗效和安全性。方法: 选择2021年9月至2022年6月规律就诊于山西省汾阳医院风湿免疫科的难治性中重度活动性RA患者30例进行前瞻性临床研究，其中，23例患者采用≥2种传统合成改善病情抗风湿药(disease modifying anti-rheumatic drugs，DMARDs)(至少包括甲氨蝶呤或来氟米特)治疗6个月以上，7例患者采用传统合成DMARDs联合肿瘤坏死因子拮抗剂治疗。将DMARDs调整为艾拉莫德联合托法替布，共治疗12周，收集患者治疗前，治疗4周、8周及12周时的临床资料：肿胀关节数(swollen joints count，SJC)、疼痛关节数(tender joints count，TJC)、晨僵时间、临床疾病活动指数(clinical disease activity index，CDAI)、健康状况评估问卷(health status assessment questionnaire，HAQ)、28个关节计数的疾病活动评分(28-joint disease activity score，DAS28)。记录患者的红细胞沉降率(erythrocyte sedimentation rate, ESR)、C反应蛋白(C-reactive protein, CRP)、血小板(platelet, PLT)、类风湿因子(rheumatoid factor, RF)、球蛋白、抗环瓜氨酸肽(cyclic citrullinated peptide, CCP)抗体等实验室检查结果，记录患者的用药情况，比较患者疾病活动指标的变化情况，记录药物不良反应。结果: 比较治疗前后的ESR、CRP、RF、PLT、SJC、TJC、基于ESR的DAS28(DAS28-ESR)、晨僵时间、HAQ、CDAI、抗CCP抗体，差异均有统计学意义(P < 0.05)，而治疗前后的球蛋白比较差异无统计学意义(P>0.05)。艾拉莫德联合托法替布治疗期间，所有患者均未发生白细胞减少、肝酶明显升高、过敏、血栓栓塞等严重不良反应。结论: 艾拉莫德联合托法替布治疗难治性中重度RA，可通过降低炎性指标改善患者的近期临床症状，且安全性良好。

关键词: 类风湿关节炎, 艾拉莫德, 托法替布, 治疗结果, 安全

Abstract:

Objective: To investigate the efficacy and safety of iguratimod combined with tofacitinib in patients with difficult-to-treat moderate-to-severe rheumatoid arthritis (RA). Methods: In this prospective clinical study, 30 patients with difficult-to-treat moderate-to-severe RA who attended the Department of Rheumatology and Immunology of Shanxi Province Fenyang Hospital from September 2021 to June 2022 were selected. Twenty-three patients enrollment had been treated with 2 or more conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) for more than 6 months. At least, methotrexate or leflunomide was included. Seven patients were treated with conventional synthetic DMARDs combined with tumor necrosis factor antagonists. Because all the patients had not reached the target of treatment, the combination treatment regimen of DMARDs was changed to iguratimod and tofacitinib. The observation period was 12 weeks. Clinical data were collected before and after treatment. At the end of 4 weeks, 8 weeks and 12 weeks, the clinical data were collected such as swollen joints count (SJC), tender joints count (TJC), time of morning stiffness, clinical disease activity index (CDAI), health status assessment questionnaire (HAQ), and 28-joint disease activity score (DAS28) were included. We collected laboratory indicators, recorded the patient's medication, and observed some changes to see if any adverse drug reactions occurred during the treatment. Results: There were significant differences in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), platelet (PLT), SJC, TJC, DAS28 based on ESR(DAS28-ESR), time of morning stiffness, HAQ, CDAI, and anti-cyclic citrullinated peptide antibody before and after treatment. The differences had statistical significance (P < 0.05). There was no statistical differences in globulin before and after treatment (P>0.05). During the treatment of iguratimod combined with tofacitinib, there was no serious adverse reactions such as leukopenia, significant elevation of liver enzymes, allergy or thromboemblolic events that occurred in all the patients. Conclusion: Iguratimod combined with tofacitinib in the treatment of difficult-to-treat moderate-to-severe RA may have efficacy. The machanism was improving the patients' recent clinical symptoms by reducing inflammatory indexes. This combination treatment regimen with iguratimod and tofacitinib has a good safety profile.

Key words: Rheumatoid arthritis, Iguratimod, Tofacitinib, Treatment outcome, Safety

中图分类号: 

  • R593.22

表1

患者入组前的用药情况(n=30)"

Usage of drugs n (%)
Two csDMARDs 21 (70.00)
    MTX and HCQ 6 (20.00)
    MTX and SSZ 9 (30.00)
    MTX and IGU 3 (10.00)
    LEF and IGU 2 (6.67)
    LEF and HCQ 1 (3.33)
Three csDMARDs 2 (6.66)
    MTX, HCQ and SSZ 1 (3.33)
    LEF, HCQ and SSZ 1 (3.33)
csDMARDs and bDMARDs 7 (23.34)
    MTX and etanercept 3 (10.00)
    MTX and adalimumab 1 (3.33)
    LEF and etanercept 2 (6.64)
LEF and adalimumab 1 (3.33)
Prednisone (≤10 mg/d) 22 (73.33)
NSAIDs 18 (60.00)

表2

治疗前后疾病活动相关指标的比较(n=30)"

Project Before treatment, M (P25, P75) After treatment, M (P25, P75) Wald χ2 P
4 weeks 8 weeks 12 weeks
ESR/(mm/h) 60.00 (42.75, 82.75) 30.05 (16.5, 53.00) 17.50 (10.05, 30.50) 9.00 (4.25, 13.50) 134.183 <0.001*
CRP/(mg/L) 22.97 (11.81, 43.89) 6.94 (2.20, 15.86) 3.45 (1.03, 6.41) 1.30 (0.33, 3.10) 37.586 <0.001*
RF/(IU/mL) 82.30 (22.43, 308.70) 53.00 (19.38, 202.50) 39.50 (13.40, 111.63) 18.50 (7.23, 59.83) 15.759 0.001*
PLT/(×109/L) 316.50 (234.50, 394.50) 250.50 (210.50, 308.00) 242.50 (213.00, 283.00) 242.00 (213.00, 313.50) 19.278 <0.001*
Globulin/(g/L) 31.60 (25.42, 34.02) 28.05 (24.72, 33.05) 27.30 (23.62, 32.55) 5.648 0.130
DAS28-ESR 4.77 (4.13, 5.60) 3.67 (2.75, 4.10) 1.83 (1.08, 2.94) 1.14 (0.72, 2.62) 393.417 <0.001*
Morning stiffness/min 90.00 (57.50, 120.00) 52.50 (27.50, 120.00) 20.00 (10.00, 41.25) 5.00 (0.00, 16.25) 122.857 <0.001*
SJC 8.50 (5.75, 12.00) 5.00 (2.00, 8.00) 2.50 (1.00, 4.00) 1.00 (0.00, 3.00) 129.482 <0.001*
TJC 9.51 (6.00, 14.25) 7.00 (4.00, 10.00) 3.00 (2.00, 6.00) 2.00 (2.00, 5.50) 153.105 <0.001*
CDAI 32.00 (22.75, 43.00) 24.00 (13.50, 28.00) 9.50 (5.00, 15.00) 5.00 (1.75, 9.75) 211.187 <0.001*
HAQ 10.00 (7.00, 17.00) 6.50 (4.00, 10.00) 5.00 (2.75, 7.25) 2.00 (1.75, 9.75) 141.037 <0.001*
ACPA/(IU/mL) 246.00 (153.75, 294.75) 138.00 (106.50, 232.50) 56.986 <0.001*

表3

治疗前后疾病活动指标比较(经广义估计方程模型分析，以治疗前为对照进行时间效应多重比较)"

Project Group β(95%CI) Wald χ2 P
ESR Before treatment
4 weeks -27.867 (-36.365, -19.368) 41.302 <0.001*
8 weeks -40.433 (-49.870, -30.997) 70.524 <0.001*
12 weeks -50.600 (-59.823, -41.377) 115.614 <0.001*
CRP Before treatment
4 weeks -24.367 (-36.299, -12.435) 16.020 <0.001*
8 weeks -30.088 (-42.632, -17.543) 22.100 <0.001*
12 weeks -32.867 (-45.684, -20.049) 25.257 <0.001*
RF Before treatment
4 weeks -42.168 (-69.685, -14.652) 9.022 0.003*
8 weeks -86.759 (-131.934, -41.584) 14.169 <0.001*
12 weeks -139.566 (-222.283, -56.849) 10.936 0.001*
PLT Before treatment
4 weeks -49.900 (-79.813, -19.987) 10.690 <0.001*
8 weeks -56.833 (-83.675, -29.991) 17.221 <0.001*
12 weeks -60.933 (-88.237, -33.630) 19.132 <0.001*
SJC Before treatment
4 weeks -3.733 (-4.595, -2.872) 72.147 <0.001*
8 weeks -6.567 (-7.701, -5.433) 128.777 <0.001*
12 weeks -7.833 (-9.219, -6.447) -15.346 <0.001*
TJC Before treatment
4 weeks -4.000 (-5.205, -2.795) 42.353 <0.001*
8 weeks -6.700 (-8.216, -5.184) 75.053 <0.001*
12 weeks -8.933 (-10.429, -7.438) 137.104 <0.001*
DAS28-ESR Before treatment
4 weeks -1.286 (-1.553, -1.020) 89.469 <0.001*
8 weeks -2.893 (-3.228, -2.557) 285.404 <0.001*
12 weeks -3.459 (-3.801, -3.117) 392.627 <0.001*
Morning stiffness Before treatment
4 weeks -21.000 (-29.333, -12.667) 24.395 <0.001*
8 weeks -57.267 (-68.908, -45.625) 92.962 <0.001*
12 weeks -73.833 (-87.535, -60.132) 111.545 <0.001*
HAQ Before treatment
4 weeks -4.300 (-5.201, -3.399) 87.446 <0.001*
8 weeks -6.700 (-7.877, -5.523) 124.579 <0.001*
12 weeks -8.900 (-10.394, -7.406) 136.386 <0.001*
CDAI Before treatment
4 weeks -11.217 (-13.516, -8.917) 91.402 <0.001*
8 weeks -21.650 (-25.044, -18.256) 156.323 <0.001*
12 weeks -26.350 (-30.079, -22.621) 191.827 <0.001*
ACPA Before treatment
After treatment -68.267 (-85.991, -50.542) 56.986 <0.001*

表4

治疗期间疾病活动构成比的比较(n=30)"

Items Remission, n (%) Low disease activity, n (%) Moderate disease activity, n (%) High disease activity, n (%) Z P
Before treatment 0 (0) 0 (0) 16 (53.33) 14 (46.67)
4 weeks 7 (23.33) 3 (10.00) 15 (50.00) 5 (16.67) -3.491 <0.05*
8 weeks 15 (50.00) 10 (33.33) 3 (10.00) 2 (6.67) -5.828 <0.05*
12 weeks 21 (70.00) 7 (23.33) 2 (6.67) 0 (0) -6.704 <0.05*

表5

治疗4、8、12周时疾病活动指标与治疗前比较(t检验)"

Items ESR CRP RF PLT DAS28-ESR Morning stiffness SJC TJC CDAI HAQ ACPA
4 weeks t -7.51 -5.23 -1.54 -4.18 -8.16 -3.81 -7.31 -6.61 -8.10 -8.58
P <0.05* <0.05* 0.12 <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05*
8 weeks t -10.91 -6.46 0.002 -4.77 -18.35 -10.40 -12.86 -11.08 -15.64 -15.64
P <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05*
12 weeks t -13.65 -7.06 -5.12 -5.11 -21.95 -12.86 -15.34 -14.77 -19.04 -19.04 -7.42
P <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05* <0.05*

图1

治疗前后DAS28-ESR评分构成比的比较(n=30)"

表6

治疗前后常规实验室检查指标比较(n=30)"

Project Before treatment, M (P25, P75) After treatment, M (P25, P75) Wald χ2 P
4 weeks 8 weeks 12 weeks
WBC/(×109/L) 7.35 (6.48, 8.84) 6.74 (5.57, 7.90) 6.39 (5.08, 7.73) 6.07 (5.43, 7.56) 5.090 0.165
RBC/(×1012/L) 4.27 (4.09, 4.67) 4.40 (4.17, 4.65) 4.51 (4.25, 4.90) 4.49 (4.26, 4.83) 15.936 0.001*
HGB/(g/L) 125.50 (111.75, 137.25) 122.00 (114.75, 129.25) 126.50 (114.75, 142.50) 132.00 (121.00, 141.75) 10.300 0.016*
ALT/(U/L) 17.00 (15.00, 27.00) 18.50 (14.00, 23.25) 17.00 (15.00, 24.00) 18.50 (15.75, 25.75) 9.138 0.028*
AST/(U/L) 18.50 (15.00, 25.25) 18.50 (14.00, 23.00) 19.50 (15.00, 24.00) 18.50 (15.00, 28.00) 1.905 0.592
GGT/(U/L) 19.00 (14.00, 31.50) 18.00 (14.75, 22.50) 15.50 (12.75, 23.50) 15.00 (12.00, 22.50) 2.727 0.436
Total protein/(g/L) 74.00 (71.87, 76.62) 76.00 (69.20, 77.85) 73.25 (70.75, 77.47) 73.30 (70.00, 82.22) 2.417 0.490
Albumin/(g/L) 43.95 (41.60, 46.15) 44.70 (42.92, 47.35) 45.55 (42.77, 47.52) 45.65 (43.30, 47.45) 5.845 0.119
Cr/(μmol/L) 62.50 (56.75, 72.50) 65.00 (59.00, 76.30) 67.00 (56.75, 73.50) 66.00 (58.75, 77.00) 5.149 0.161
BUN/(mmol/L) 4.40 (3.70, 5.02) 4.60 (4.20, 5.45) 4.70 (4.40, 6.10) 4.65 (4.37, 5.32) 8.214 0.042*

表7

治疗前后常规检测指标的比较(n=30)"

Project Group β(95%CI) Wald χ2 P
RBC Before treatment
4 weeks 0.369 (0.022, 0.717) 4.334 0.037*
8 weeks 0.261 (0.063, 0.460) 6.674 0.010*
12 weeks 0.532 (0.234, 0.831) 12.227 <0.001*
HGB Before treatment
4 weeks -2.433 (-9.203, 4.336) 0.496 0.481
8 weeks 2.300 (-3.816, 8.416) 0.543 0.461
12 weeks 6.500 (-1.942, 14.942) 2.277 0.131
ALT Before treatment
4 weeks -4.933 (-8.176, -1.690) 8.890 0.003*
8 weeks -3.633 (-7.479, 0.212) 3.429 0.064*
12 weeks -2.333 (-6.553, 1.886) 1.175 0.278
BUN Before treatment
4 weeks 0.297 (-0.124, 0.717) 1.911 0.167
8 weeks 4.237 (-0.886, 9.359) 2.628 0.105
12 weeks 0.360 (0.037, 0.683) 4.766 0.029*
1 Smolen JS , Landewé RBM , Bijlsma JWJ , et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying anti-rheumatic drugs: 2019 update[J]. Ann Rheum Dis, 2020, 79 (6): 685- 699.
doi: 10.1136/annrheumdis-2019-216655
2 de Hair MJH , Jacobs JWG , Schoneveld JLM , et al. Difficult-to-treat rheumatoid arthritis: An area of unmet clinical need[J]. Rheumatology (Oxford), 2018, 57 (7): 1135- 1144.
3 Buch MH . Defining refractory rheumatoid arthritis[J]. Ann Rheum Dis, 2018, 77 (7): 966- 969.
doi: 10.1136/annrheumdis-2017-212862
4 Smolen JS , Aletaha D , Mcinnes IB . Rheumatoid arthritis[J]. Lancet, 2016, 388 (10055): 2023- 2038.
doi: 10.1016/S0140-6736(16)30173-8
5 Aletaha D , Neogi T , Silman AJ , et al. 2010 rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative initiative[J]. Arthritis Rheum, 2010, 62 (9): 2569- 2581.
doi: 10.1002/art.27584
6 Wu D , Luo Y , Li T , et al. Systemic complications of rheumatoid arthritis: Focus on pathogenesis and treatment[J]. Front Immunol, 2022, 13, 1051082.
doi: 10.3389/fimmu.2022.1051082
7 Sun X , Li R , Cai Y , et al. Clinical remission of rheumatoid arthritis in a multi center real-world study in Asia-Pacific region[J]. Lancet Reg Health West Pac, 2021, 15, 100240.
doi: 10.1016/j.lanwpc.2021.100240
8 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, 23 (10): 689- 693.
9 Nagy G , Roodenrijs NMT , Welsing PM , et al. EULAR definition of difficult-to-treat rheumatoid arthritis[J]. Ann Rheum Dis, 2021, 80 (1): 31- 35.
doi: 10.1136/annrheumdis-2020-217344
10 Xie S , Li S , Tian J , et al. Iguratimod as a new drug for rheumatoid arthritis: Current landscape[J]. Front Pharmacol, 2020, 11, 73.
doi: 10.3389/fphar.2020.00073
11 Xu Y , Zhu Q , Song J , et al. Regulatory effect of iguratimod on the balance of Th subsets and inhibition of inflammatory cytokines in patients with rheumatoid arthritis[J]. Mediators Inflamm, 2015, 2015, 356040.
12 Wen L , Jiang W , Zhou M , et al. Effect of combined application of iguratimod in the treatment of active rheumatoid arthritis on bone metabolism, Th17 cells and Treg cells[J]. Am J Transl Res, 2021, 13 (3): 1676- 1684.
13 Liu S , Song LP , Li RB , et al. Iguratimod promotes transformation of mononuclear macrophages in elderly patients with rheumatoid arthritis by nuclear factor-κB pathway[J]. World J Clin Cases, 2021, 9 (10): 2181- 2191.
doi: 10.12998/wjcc.v9.i10.2181
14 Li CH , Ma ZZ , Jian LL , et al. Iguratimod inhibits osteoclastoge-nesis by modulating the RANKL and TNF-α signaling pathways[J]. Int Immunopharmacol, 2021, 90, 107219.
doi: 10.1016/j.intimp.2020.107219
15 Kondo N , Kuroda T , Kobayashi D . Cytokine networks in the pa-thogenesis of rheumatoid arthritis[J]. Int J Mol Sci, 2021, 22 (20): 10922.
doi: 10.3390/ijms222010922
16 Malemud CJ . The role of the JAK/STAT signal pathway in rheumatoid arthritis[J]. Ther Adv Musculoskelet Dis, 2018, 10 (5/6): 117- 127.
17 疏金玲, 张玲玲, 魏伟. 酪氨酸激酶抑制剂治疗类风湿关节炎研究进展[J]. 中国药理学与毒理学杂志, 2020, 34 (9): 713- 720.
18 Puigdevall L , Michiels C , Stewardson C , et al. JAK/STAT: Why choose a classical or an alternative pathway when you can have both?[J]. J Cell Mol Med, 2022, 26 (7): 1865- 1875.
doi: 10.1111/jcmm.17168
19 戴冰冰, 刘佳丽, 李宁宁, 等. 托法替布治疗难治性中重度类风湿关节炎的疗效及安全性[J]. 实用临床医药杂志, 2022, 26 (11): 122- 126.
20 Zheng N , Guo C , Wu R . Iguratimod is effective in refractory rheumatoid arthritis patients with inadequate response to metho-trexate-cyclosporin A-hydroxychloroquine-prednisone[J]. Scand J Rheumatol, 2018, 47 (5): 422- 424.
doi: 10.1080/03009742.2017.1376109
21 Mizutani S , Kodera H , Sato Y , et al. Clinical effectiveness of iguratimod based on real-world data of patients with rheumatoid arthritis[J]. Clin Rheumatol, 2021, 40 (1): 123- 132.
doi: 10.1007/s10067-020-05208-y
22 Inoue A , Nozaki Y , Hirooka Y , et al. The effectiveness and retention rate of iguratimod in Japanese rheumatoid arthritis patients with/without methotrexate in daily medical care[J]. Life (Basel), 2020, 10 (11): 261.
23 Ouyang D , Ma YZ , Zou J , et al. Effectiveness and safety of iguratimod monotherapy or combined with methotrexate in treating rheumatoid arthritis: A aystematic review and meta-analysis[J]. Front Pharmacol, 2022, 13, 911810.
24 Smolen JS , Landewe R , Breedveld FC , et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update[J]. Ann Rheum Dis, 2014, 73 (3): 492- 509.
25 Angelini J , Talotta R , Roncato R , et al. JAK-inhibitors for the treatment of rheumatoid arthritis: A focus on the present and an outlook on the future[J]. Biomolecules, 2020, 10 (7): 1002.
26 张春燕, 范小冬, 秦元, 等. JAK抑制剂托法替布治疗类风湿性关节炎效果的Meta分析[J]. 第三军医大学学报, 2018, 40 (6): 543- 550.
27 Sands BE , Taub PR , Armuzzi A , et al. Tofacitinib treatment is associated with modest and reversible increases in serum lipids in patients with ulcerative colitis[J]. Clin Gastroenterol Hepatol, 2020, 18 (1): 123- 132.e3.
28 Taylor PC , Kremer JM , Emery P , et al. Lipid profile and effect of statin treatment in pooled phase Ⅱ and phase Ⅲ baricitinib studies[J]. Ann Rheum Dis, 2018, 77 (7): 988- 995.
[1] 步召德, 冯梦宇, 季科. 早期胃癌行前哨淋巴结导航手术的实践与思考[J]. 北京大学学报（医学版）, 2026, 58(2): 239-243.
[2] 魏慧, 张警丰, 姚中强, 赵金霞. 类风湿关节炎合并慢性病贫血患者的临床特征及相关因素[J]. 北京大学学报（医学版）, 2026, 58(2): 307-312.
[3] 李伟浩, 张学民, 李伟, 张韬, 张小明. 胸主动脉腔内修复术左肱动脉穿刺点使用血管缝合器处理的临床效果[J]. 北京大学学报（医学版）, 2026, 58(2): 388-392.
[4] FarinEbrahimi, 冯志强, FarazEbrahimi, 韩玮华, 于子杨, 贾宽宽, 安金刚. 上颌药物相关性颌骨坏死的不同分期手术治疗效果[J]. 北京大学学报（医学版）, 2026, 58(1): 107-114.
[5] 潘莲菲, 李文静, 王瑞洋, 焦剑, 曹战强, 高丽, 释栋. 口服抗生素辅助牙周机械治疗对重度牙周炎的短期疗效及影响因素[J]. 北京大学学报（医学版）, 2026, 58(1): 30-36.
[6] 吴滔, 林建子, 朱亚锋, 马剑达, 贾霈雯, 杨莉娟, 潘婕, 邹耀威, 杨迎, 卢烨, 戴冽. 血清蛋白质谱筛选及验证类风湿关节炎患者肌肉量减少的生物标志物[J]. 北京大学学报（医学版）, 2025, 57(6): 1024-1031.
[7] 丁艳, 王丽芳, 李超然, 卢哲敏, 石连杰. 利妥昔单抗成功治疗类风湿关节炎合并IgG4相关性疾病1例[J]. 北京大学学报（医学版）, 2025, 57(6): 1203-1207.
[8] 杨菊, 徐婧, 戴菊华, 石连杰. Lumican蛋白在类风湿关节炎患者血清中的表达及其与疾病和免疫活动的相关性[J]. 北京大学学报（医学版）, 2025, 57(5): 911-918.
[9] 冯亮华, 洪丽荣, 陈雨佳, 蔡学明. 泛素特异性蛋白酶35对类风湿关节炎成纤维样滑膜细胞铁死亡的作用及机制[J]. 北京大学学报（医学版）, 2025, 57(5): 919-925.
[10] 康一帆, 葛严军, 吕晓鸣, 谢尚, 单小峰, 蔡志刚. 即刻种植体支持式义齿修复的血管化髂骨瓣重建下颌骨缺损[J]. 北京大学学报（医学版）, 2025, 57(1): 78-84.
[11] 贾霈雯, 杨迎, 邹耀威, 欧阳志明, 林建子, 马剑达, 杨葵敏, 戴冽. 类风湿关节炎患者低肌肉量综合征的临床特征及其对躯体功能的影响[J]. 北京大学学报（医学版）, 2024, 56(6): 1009-1016.
[12] 马豆豆, 卢哲敏, 郭倩, 朱莎, 古今, 丁艳, 石连杰. 小剂量利妥昔单抗成功治疗类风湿关节炎合并重症肌无力1例[J]. 北京大学学报（医学版）, 2024, 56(6): 1110-1114.
[13] 闫蕊, 柯丹, 张妍, 李丽, 苏焕然, 陈伟, 孙明霞, 刘晓敏, 罗靓. 血清趋化因子CXCL-10和涎液化糖链抗原6水平在类风湿关节炎合并肺间质病变患者中的诊断和病情评估价值[J]. 北京大学学报（医学版）, 2024, 56(6): 956-962.
[14] 赵亮, 史成龙, 马柯, 赵静, 王潇, 邢晓燕, 莫万星, 练益瑞, 高超, 李玉慧. 抗合成酶综合征重叠类风湿关节炎患者的免疫学特征[J]. 北京大学学报（医学版）, 2024, 56(6): 972-979.
[15] 韩艺钧, 陈小莉, 李常虹, 赵金霞. 甲氨蝶呤在类风湿关节炎患者中的应用现状[J]. 北京大学学报（医学版）, 2024, 56(6): 994-1000.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
ISSN 1671-167X
CN 11-4691/R
主管单位：中华人民共和国教育部
主办单位：北京大学
地址： 北京市海淀区学院路38号 北京大学医学部 《北京大学学报（医学版）》
邮编：100191
电话：010-82801551
Email： xbbjb2@bjmu.edu.cn

《北京大学学报（医学版）》
微信公众号
版权所有 © 2018 《北京大学学报（医学版）》编辑部