Background The outcomes of strategies using biologics to treat rheumatoid arthritis (RA) have been very successful. However, the responses of patients to such therapy are not predictable in advance and useful factors remain unclear despite investigations into the effects of biologics. Furthermore, the slow action of tocilizumab (TCZ) complicates understanding of its early clinical effect.
Objectives We aimed to identify factors predicting the early effects of TCZ therapy in patients with RA in a clinical trial of the Predictors of Effectiveness in Tocilizumab Therapy (PETITE). The study registration number is UMIN000002246.
Methods We selected patients with RA treated with TCZ at Osaka City University and related hospitals. Forty-eight patients (four males, 44 females; mean age, 59.6±14.2 y; disease duration, 11.9±10.1 y) were treated with TCZ for >24 weeks. Serum IL-1 beta, D-dimer and fibrinogen were measured before and after four weeks of TCZ therapy. The effect of TCZ and clinical changes were assessed as changes in the DAS28-ESR between baseline and 24 weeks.
Results The DAS28-ESR decreased from 5.49 to 2.71 and from 5.24 to 3.03 when serum IL-1β decreased after four weeks and was below detection limit at baseline, respectively, and from 5.02 to 3.33 in the group in which serum IL-1β increased after four weeks.
A decrease in fibrinogen values significantly correlated with DAS28-ESR, whereas D-dimer did was not associated with predicting clinical outcomes.
Conclusions The decrease in DAS28-ESR was larger in the group with decreased, than increased serum IL-1β levels at four weeks and a decrease in fibrinogen significantly correlated with DAS28-ESR. Thus, changes in baseline serum IL-1 β and fibrinogen values after four weeks ofTCZ administration are potent tools for identifying new candidate biomarkers to predict the response to TCZ at 24 weeks.
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Disclosure of Interest T. Okano: None Declared, T. Koike Grant/Research support from: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, M. Tada: None Declared, Y. Sugioka: None Declared, K. Mamoto: None Declared, S. Wakitani: None Declared, H. Nakamura Grant/Research support from: Chugai Pharmaceutical, Astellas Pharma Inc.,Janssen Pharmaceutica, GlaxoSmithKline, Pfizer Inc. and Daiichi Sankyo, INC., Speakers Bureau: Ono Pharmaceutical