Background Better objective measures are needed to evaluate the responses to biologics in rheumatoid arthritis (RA) patients because such responses are not predictable and useful indicators remain unclear. Furthermore, to predict the early effect of tocilizumab (TCZ) is difficult because inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) become negative regardless of clinical effect.
Objectives We aimed to identify factors that could predict the early effects of TCZ therapy in patients with RA in the clinical Predictors of Effectiveness in Tocilizumab Therapy (PETITE) trial (Registration number, UMIN000002246).
Methods We treated 60 patients with RA (male, n = 5; female, n = 55) with TCZ for 52 weeks between September 2009 and December 2011 at Osaka City University Hospital and related hospitals. Serum interleukin-1 beta (IL-1β), D-dimer and fibrinogen were measured before and after 4 weeks of TCZ therapy. The effect of TCZ and clinical changes were assessed as changes in the disease activity score (DAS) 28-ESR and clinical disease activity index (CDAI) between baseline and 52 weeks. The last observation carried forward (LOCF) and linear imputation were used in the analysis of clinical efficacy when data were missing.
Results Mean age and disease duration were 60.4 ± 14.9 (22 – 85) and 11.2 ± 10.2 (0 – 45) years, respectively. The DAS28-ESR and the ratio of the CDAI decrease were significantly decreased in the group below, than within the upper detection limits of serum IL-1β after 4 weeks (-2.36 vs. -1.66; p < 0.01). The increase in IL-1β after 4 weeks predicted less of a decrease in the DAS28-ESR at 52 weeks. Baseline levels and changes in D-dimer and fibrinogen between baseline and after 4 weeks did not predict changes in the DAS28-ESR and CDAI at 52 weeks.
Conclusions The decreases in the DAS28-ESR and in the ratio of the CDAI decrease at 52 weeks was larger in the group below, than in the upper detection limit of serum IL-1β at 4 weeks. Thus, serum IL-1 β levels after 4 weeks of TCZ administration are potent tools for identifying new candidate biomarkers with which to predict responses to TCZ at 52 weeks.
References Gibbons LJ, Hyrich KL. Biologic therapy for rheumatoid arthritis: clinical efficacy and predictors of response. BioDrugs. 2009;23:111-24.
Disclosure of Interest T. Okano: None Declared, T. Koike Speakers bureau: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, M. Tada Grant/research support from: Japan Osteoporosis Foundation grant 2013, Y. Sugioka: None Declared, K. Mamoto: None Declared, K. Inui: None Declared, H. Nakamura: None Declared