Introduction. Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study wasto assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease.
Methods. ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11(84.61%) female. The average age of patients was 53.27+/−10.68. Patients received 8mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire.
Results. Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission.
Conclusion. The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.
7. Heinrich PC, et al. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003; 374: 1-2.
8. Cronstein BN. Interleukin-6: A key mediator of systemic and local symptoms in rheumatoid arthritis. Bull NYU Hosp Jt Dis 2007; 65(suppl1): S11-S15.
9. Emery P, Keystone E, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patient with rheumatoid arthritis refractory to anti-TNF biologic: results from a 24-week multicentre randomized placebo controlled trial. Ann Rheum Dis 2008; 67: 1516-1523. doi:10.1136/ard.2008.092932.
10. Dougados M, et al. Tocilizumab (TCZ) plus methotrexate (MTX) does not have superior clinical efficacy to TCZ alone in RA patients with inadequate response to MTX: 24-week results of the ACT-RAY study. Arthritis Rheum 2011;63(10 Suppl): S1032-10Sibilia J, et al. Ann Rheum Dis 2011; 70(Suppl. 3): 466.
11. Yen J.-H. Treatment of early rheumatoid arthritis in developing countries. Biologics or disease-modifying anti-rheumatic drugs? Biomedecine & Pharmacotherapy 2006, 60(10): 688-692.
12. Madhok R, et al. Serum interleukin 6 levels in rheumatoid arthritis: correlations with laboratory indices of disease activity. Ann Rheum Dis 1993; 52: 232-234.
13. Jones G, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 2010; 69: 88-96.
14. Smolen JS, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomized. Lancet 2008; 371: 987-997.
15. Fleischman RM, 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 Rheumatol 2013; 40: 113-126.
16. Strand V, et al. Improvements in health-related quality of life after treatment with tocilizumab in patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study. Rheumatology 2012; 51: 186011869 doi:10.1093/rheumatology/kes131.
17. Genovese MC, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic tocilizumab in combination with traditional disease-modifying antirheumatic drug. Arthritis Rheum 2008; 58: 2968-2980.
18. Josef S Smolen, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Published by group.bmj.com. Ann Rheum Dis 2013; 0: 1-18. doi:10.1136/annrheumdis-2013-204573.
19. Cem Gabay, et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. The Lancet 2013; 381(9877): 1541-1550.