Clinical Observation on Tocilizumab in Treating Resistant Rheumatoid Arthritis_West China Medical Journal

Authors：

 ZHANGJing , LIUJian , ZHOUQiao , WUTong ,  ZHOUBin

Department of Rheumatology and Immunology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P. R. China;

Corresponding author：

ZHOUBin, Email: bingb2917@126.com

Keywords：

Tocilizumab; Rheumatoid arthritis; Clinical observation

DOI：

10.7507/1002-0179.20150467

Video：

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Objective To study the short-term efficacy and safety of tocilizumab in treating patients with active and resistant rheumatoid arthritis (RRA). Method Forty patients with RRA treated with tocilizumab between October 2013 and October 2014 were included in our study. The combined drug treatment was continued with the addition of tocilizumab 8 mg/kg per four weeks. The clinical responses and laboratory parameters were evaluated at the baseline, week 1, 4, 12, 16 and 24, and week 4 and 8 of tocilizumab withdrawal. Results Tocilizumab was effective for several clinical lesions and laboratorial parameters at all time points. With the extension of treatment, the effect was better. At week 1, the visual analogue scale score of pain by patients, erythrocyte sedimentation rate, C-reactive protein (CRP), disease activity score 28 (DAS28) and health assessment questionnaire (HAQ) results decreased significantly (P<0.05). At week 12, the inflammatory biomarkers of all patients were normal, and 62.9% (22/35) of the patients achieved American College of Rheumatology (ACR)20, and 28.6% (10/35) of the patients achieved ACR50. At week 24, twelve patients achieved ACR50 and low activity (DAS28 score≤3.2), and the score of HAQ was minimum (3.1±1.6). The score of HAQ was significantly different between week 24 and the baseline (20.2±6.7) (P<0.01). All parameters were not significantly changed at week 4 of tocilizumab withdrawal compared with those before the withdrawal. Most parameters increased significantly at week 8 of tocilizumab withdrawal compared with week 4 of withdrawal (P<0.01) except for swollen joints, CRP, DAS28 and HAQ. The main adverse reactions were abnormal hepatic function and dyslipidemia followed by leukopenia. Only one patient stopped treatment because of adverse reaction. Conclusions Tocilizumab has rapid efficacy onset and good safety. After tocilizumab withdrawal, the efficacy can be maintained for 4 to 8 weeks.

Citation： ZHANGJing, LIUJian, ZHOUQiao, WUTong, ZHOUBin. Clinical Observation on Tocilizumab in Treating Resistant Rheumatoid Arthritis. West China Medical Journal, 2015, 30(9): 1633-1637. doi: 10.7507/1002-0179.20150467 Copy

1.	Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American college of rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis[J]. Arthritis Care Res (Hoboken), 2012, 64(5):625-639.
2.	杨岫岩, 谢彤. 难治性类风湿性关节炎的治疗[J]. 广东医学, 2001, 22(10):893-894.
3.	Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis[J]. Cochrane Database Syst Rev, 2010 (7):CD008331.
4.	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.
5.	Md Yusof MY, Emery P. Targeting interleukin-6 in rheumatoid arthritis[J]. Drugs, 2013, 73(4):341-356.
6.	王永红, 王可丽, 许素琴, 等. 难治性类风湿关节炎临床特点分析[J]. 中华风湿病学杂志, 2005, 5(9):171.
7.	Smolen JS, Landewé 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.
8.	Fleischmann RM, Halland AM, Brzosko M, et al. Tocilizumab inhibits structural joint damage and improves physical function in patients with rheumatoid arthritis and inadequate responses to methotrexate:LITHE study 2-year results[J]. J Rheumatol, 2013, 40(2):113-126.
9.	Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study):a double-blind, placebo-controlled, randomised trial[J]. Lancet, 2008, 371(9617):987-997.
10.	Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals:results from a 24-week multicentre randomised placebo-controlled trial[J]. Ann Rheum Dis, 2008, 67(11):1516-1523.
11.	Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs:the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study[J]. Arthritis Rheum, 2008, 58(10):2968-2980.
12.	Kremer JM, Fleischmann RM, Halland A, et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with an inadequate response to methotrexate:the LITHE study[J]. Arthritis Rheum, 2008, 58(12):4031.
13.	史群, 赵岩, 鲍春德, 等. 托珠单抗联合改善病情抗风湿药治疗类风湿关节炎的多中心、随机、双盲、安慰剂对照临床研究[J]. 中华内科杂志, 2013, 52(4):323-329.

1. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American college of rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis[J]. Arthritis Care Res (Hoboken), 2012, 64(5):625-639.
2. 杨岫岩, 谢彤. 难治性类风湿性关节炎的治疗[J]. 广东医学, 2001, 22(10):893-894.
3. Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis[J]. Cochrane Database Syst Rev, 2010 (7):CD008331.
4. 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.
5. Md Yusof MY, Emery P. Targeting interleukin-6 in rheumatoid arthritis[J]. Drugs, 2013, 73(4):341-356.
6. 王永红, 王可丽, 许素琴, 等. 难治性类风湿关节炎临床特点分析[J]. 中华风湿病学杂志, 2005, 5(9):171.
7. Smolen JS, Landewé 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.
8. Fleischmann RM, Halland AM, Brzosko M, et al. Tocilizumab inhibits structural joint damage and improves physical function in patients with rheumatoid arthritis and inadequate responses to methotrexate:LITHE study 2-year results[J]. J Rheumatol, 2013, 40(2):113-126.
9. Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study):a double-blind, placebo-controlled, randomised trial[J]. Lancet, 2008, 371(9617):987-997.
10. Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals:results from a 24-week multicentre randomised placebo-controlled trial[J]. Ann Rheum Dis, 2008, 67(11):1516-1523.
11. Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs:the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study[J]. Arthritis Rheum, 2008, 58(10):2968-2980.
12. Kremer JM, Fleischmann RM, Halland A, et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with an inadequate response to methotrexate:the LITHE study[J]. Arthritis Rheum, 2008, 58(12):4031.
13. 史群, 赵岩, 鲍春德, 等. 托珠单抗联合改善病情抗风湿药治疗类风湿关节炎的多中心、随机、双盲、安慰剂对照临床研究[J]. 中华内科杂志, 2013, 52(4):323-329.

West China Medical Journal

Clinical Observation on Tocilizumab in Treating Resistant Rheumatoid Arthritis

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