Background A lower dose of tocilizumab (TCZ) (e.g., 4 mg/kg/month) than the standard 8 mg/kg/month has been shown to be effective for treating rheumatoid arthritis (RA), but not all patients obtain excellent results with low doses. The dose at which a satisfactory effect is obtained appears to differ with the individual. Even though there is possibility for tapering dose of TCZ in RA while maintaining comprehensive remission, given patient preferences in addition to safety and financial concerns, the implications of this approach are far from clear.
Objectives To investigate the effectiveness of TCZ decrease strategy by monitoring serum IL-6 with sustained triple remission for RA.
Methods A total of 37 RA patients with DAS28>3.2 were enrolled in 6 STAR study after gaining their informed consent. 6STAR treatment strategy was adapted based on the criteria, which was satisfied with Disease Activity Score in 28 joints (DAS28≤2.6), Health Assessment Questionnaire Disability Index (HAQDI)≤0.5, MMP-3 normalization and serum IL-6 level<35pg/mL which was detected in healthy control under the TCZ 8mg/kg administration. Evaluations were done at every inclusion visit time. When the criteria was satisfied in RA patient without prednisolone (PSL), dose of TCZ was decreased by 80mg at the next infusion. If the RA patient were mediated with PSL, firstly, dose of PSL was decreased gradually. After the discontinuation of PSL, if the criteria were met, TCZ dose was decreased as in the above method. A month later, if the criteria were not met, TCZ was increased by 80mg. Mean baseline characteristics were as follows: age, 61.4 years; duration of disease, 118.9 months; CRP, 1.2 mg/dL; ESR, 32.9 mm/h; MMP-3, 141.5 mg/dL; DAS-28, 4.84; percentage taking methotrexate, 54.1% (mean dose, 7.0 mg/week); percentage taking PSL, 24.3% (mean dose, 4.7 mg/day). Radiographic damage was assessed by total Sharp Score (TTS). Comprehensive remission consisted of the proportions of patients showing clinical remission (DAS28<2.6), radiographic nonprogression (ΔTSS≤0.5) nd normal physical function(HAQDI≤0.5).
Results After 1 year, in 7 patients, dose of TCZ (mean decrease dose of 106mg/month) could be decreased. 7 patients showed improvements in all parameters: simplified Disease Activity Index (SDAI), 4.03; DAS-28, 1.95; CRP, 0.03 mg/dL; ESR, 4.0 mm/h; MMP-3, 89.1 mg/dL at 1 year. SDAI remission, clinical remission (DAS28<2.6), radiographic non-progression, normal physical function, and comprehensive remission rate were 33%, 100%, 67%, 100%, and 33%.
Conclusions This dose adjustment method of TCZ showed therapeutic evaluation with respect to both safety and therapeutic efficacy and identified one additional benefit in terms of long-terms cost effectiveness of TCZ treatment.
Urata Y, Uesato R, Tanaka D, et al. Treating to target matrix metalloproteinase 3 normalisation together with disease activity score below 2.6 yields better effects than each alone in rheumatoid arthritis patients: T-4 Study. Ann Rheum Dis. 2011 Oct 21. [Epub ahead of print]
Disclosure of Interest None Declared