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High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study

  • Takeuchi, Tsutomu1
  • Miyasaka, Nobuyuki2
  • Inui, Takashi3
  • Yano, Toshiro3
  • Yoshinari, Toru3
  • Abe, Tohru4
  • Koike, Takao5
  • 1 Keio University, Division of Rheumatology, Department of Internal Medicine, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan , Tokyo (Japan)
  • 2 Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan , Tokyo (Japan)
  • 3 Mitsubishi Tanabe Pharma Corporation, Ikuyaku Integrated Value Development Division, 3-2-10, Dosho-machi, Chuo-ku, Osaka, 541-8505, Japan , Osaka (Japan)
  • 4 Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan , Kawagoe, Saitama (Japan)
  • 5 Sapporo Medical Center NTT EC, South-1 West-15, Chuo-ku, Sapporo, 060-0061, Japan , Sapporo (Japan)
Published Article
Arthritis Research & Therapy
Springer Science and Business Media LLC
Publication Date
Sep 02, 2017
DOI: 10.1186/s13075-017-1401-2
Springer Nature


BackgroundAlthough both rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) are useful for diagnosing rheumatoid arthritis (RA), the impact of these autoantibodies on the efficacy of tumor necrosis factor (TNF) inhibitors has been controversial. The aim of this post hoc analysis of a randomized double-blind study (the RISING study) was to investigate the influences of RF and anti-CCP on the clinical response to infliximab in patients with RA.MethodsMethotrexate-refractory patients with RA received 3 mg/kg of infliximab from weeks 0 to 6 and then 3, 6, or 10 mg/kg every 8 weeks from weeks 14 to 46. In this post hoc analysis, patients were stratified into three classes on the basis of baseline RF/anti-CCP titers: “low/low-C” (RF < 55 IU/ml, anti-CCP < 42 U/ml), “high/high-C” (RF ≥ 160 IU/ml, anti-CCP ≥ 100 U/ml), and “middle-C” (neither low/low-C nor high/high-C). Baseline plasma TNF level, serum infliximab level, and disease activity were compared between the three classes.ResultsBaseline RF and anti-CCP titers showed significant correlations with baseline TNF and infliximab levels in weeks 2–14. Comparison of the three classes showed that baseline TNF level was lowest in the low/low-C group and highest in the high/high-C group (median 0.73 versus 1.15 pg/ml), that infliximab levels at week 14 were highest in the low/low-C group and lowest in the high/high-C group (median 1.0 versus 0.1 μg/ml), and that Disease Activity Score in 28 joints based on C-reactive protein at week 14 was lowest in the low/low-C group and highest in the high/high-C group (median 3.17 versus 3.82). A similar correlation was observed at week 54 in the 3 mg/kg dosing group, but not in the 6 or 10 mg/kg group. Significant decreases in both RF and anti-CCP were observed during infliximab treatment.ConclusionsRF/anti-CCP titers correlated with TNF level. This might explain the association of RF/anti-CCP with infliximab level and clinical response in patients with RA. Baseline RF/anti-CCP titers may serve as indices that aid infliximab treatment.Trial, NCT00691028. Retrospectively registered on 3 June 2008.

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