Background Abatacept (ABT) is a biologic drug and has been available for rheumatoid arthritis (RA) patients since 2010 in Japan. Although we have some reports describing the short-term clinical results of ABT , there has been little evidence showing the long-term results of ABT. Positivity for anti-CCP peptide has been reported that it is associated with a better response to ABT at 6 months . There have been few reports describing the association of rheumatoid factor with the long-term clinical results represented by drug retention rate.
Objectives The aim of this study is to demonstrate whether the positivity for rheumatoid factor is associated with the short-term (52 weeks) clinical response to ABT and the long-term (4 years) drug retention rate of ABT using data from a Japanese multicenter registry system for RA patients treated with biological DMARDs.
Methods Participants were consecutive 508 patients with RA who were prospectively registered in the Tsurumai Biologics Communication Registry and treated with ABT. Demographic data and the following parameters of disease activity were collected; TJC, SJC, patient global assessment, ESR, and serum CRP at baseline, 4, 12, 24, and 52 weeks. The last observation carried forward (LOCF) method was used in each analysis. Survival analysis was performed with the Kaplan-Meier method and log-rank test. We compared these clinical indices between the patients with and those without RF positivity.
Results At baseline, mean age was 65.1 years, disease duration was 13.1 years, and DAS28-CRP was 4.36. Of the 508 patients, 78.8% was female, 77.5% was RF positive (>20 mg/dl), and 42.7% had prior biologics history (Bio-switch). Percent change of DAS28-CRP was significantly greater in the RF positive group from 4 weeks throughout 52 weeks (p<0.05) (Fig. 1a). The proportion of patients that achieved EULAR moderate response was also greater in the RF positive group from 4 to 52 weeks (p<0.01) (Fig. 1b).
Overall drug retention rate was 60.0% in the RF negative and 77.5% in the RF positive group at 4 years (Fig. 2a). Discontinuation rate due to insufficient efficacy (Insufficiency) was 27.2% in the RF negative and 15.3% in the RF positive group (Fig. 2b). Discontinuation rate due to adverse events was similar between the groups (Fig. 2c). Within the bio-switch patients, the RF negative group demonstrated significantly higher discontinuation rate due to secondary failure (40.8 vs 11.0%) (Fig. 3b). The hazard ratio (HR) for secondary failure, adjusted for sex, age, disease duration, concomitant MTX and PSL, and baseline DAS28-CRP, was 4.17 (95%CI 1.20-14.45) for RF negative versus RF positive. On the other hand, RF positivity did not affect the discontinuation rate in the Bio-naïve patients (Fig. 3a).
Conclusions We found that RF positivity was associated with better short-term response to ABT. We also found that RF positivity significantly improve the long-term incidence rate of discontinuation due to secondary failure in the bio-switch patients. It is necessary to establish the strategy for additional therapeutic intervention, such as concomitant drugs, in this patients group to improve the short- and long-term clinical results of ABT.
Takahashi, et al. Rheumatology (Oxford) 2014. in press
Gottenberg JE, et al. Ann Rheum Dis 2012;1815.
Disclosure of Interest N. Takahashi: None declared, T. Kojima Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., K. Funahashi Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceuticals, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan, Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceuticals, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan