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OP0229 Both High Titer of RF/ACPA at Baseline Is Closely Linked with High Level of Baseline Plasma TNF Level Which Resulted in Low Drug Level and Low Clinical Response in Infliximab Treatment in RA Patients: Post-Hoc Analysis of A Double-Blind Clinical Study (Rising Study)
  1. T. Takeuchi1,
  2. N. Miyasaka2,
  3. T. Inui3,
  4. T. Yano3,
  5. T. Yoshinari3,
  6. T. Abe4,
  7. T. Koike5
  1. 1School of Medicine, Keio University
  2. 2Tokyo Medical and Dental University, Tokyo
  3. 3Mitsubishi Tabnabe Pharma Corporation, Osaka
  4. 4Saitama Medical Center, Saitama Medical University, Saitama
  5. 5Sapporo Medical Center NTT EC, Hokkaido, Japan

Abstract

Background Baseline RF or ACPA positivity is reported to be linked with clinical response of some non-TNF bDMARDs in RA. However, its impact on the efficacy of TNF inhibitors was controversy.

Objectives To evaluate the influence of baseline RF and ACPA “titers” on the patients characteristics and efficacy of infliximab (IFX) in RA patients using data of the RISING study, a randomized double-blind clinical study in MTX-refractory RA (ref-1, NCT00691028).

Methods In the RISING study, after patients received 3 mg/kg IFX infusion at Weeks 0, 2, and 6, they were randomly assigned to infusion of 3, 6, or 10 mg/kg IFX, every 8 weeks from Week 14 to Week 46 in a double-blind manner (n=307, all patients received 3 mg/kg treatment until Week 14). Serum IFX levels and clinical responses based on DAS28-CRP were evaluated at Weeks 14 and 54.

Results Both baseline RF and ACPA titers showed significant positive correlation with baseline plasma TNF level. We hypothesized that “both RF-High and ACPA-High” was correlated with higher TNF level. Then, we stratified the patients into 3 classes using baseline RF/ACPA titers; “Low/Low” (RF: <55 U/ml, ACPA: <42 U/ml), “High/High” (RF: ≥160 U/ml, ACPA: ≥100 U/ml), and “Middle” (did not meet above criteria for either class), and compared baseline patient characteristics, serum IFX level, and DAS28-CRP among these 3 classes.

Among above 3 classes, significant difference was observed in plasma baseline TNF level, which was previously reported to be closely correlated with low serum IFX level, and low clinical response (ref-2); low TNF level in Low/Low class, high TNF level in High/High class, and intermediate value in Middle class (median: 0.73, 1.15, and 0.91 pg/ml, respectively, p<0.0001). In addition, high serum IFX level and low DAS28-CRP in Low/Low class, low serum IFX level and high DAS28-CRP in High/High class, and intermediate values in Middle class were observed at Week 14. In Low/Low, Middle, High/High classes, median IFX levels at Week 14 were 1.5, 0.7, and 0.4 μg/ml, respectively (p=0.0004), and median DAS28-CRP at Week 14 were 3.17, 3.53, and 3.82, respectively (p=0.0256). Similar tendency was observed at Week 54 in patients who continued 3 mg/kg treatment, but not in those who received dose-escalation from 3 to 6 or 10 mg/kg after Week 14.

Conclusions High titers of both RF/ACPA at baseline is correlated with high baseline plasma TNF level which might be resulted in low IFX level and low clinical response in patients with continuing 3 mg/kg treatment, but not in patients receiving 6 or 10 mg/kg treatment. Baseline RF/ACPA might be the index of dose-escalation of IFX in RA.

  1. Takeuchi T, et al. Mod Rheumatol 2009;19:478. ref-2: Takeuchi T, et al. Ann Rheum Dis 2011;70:1208.

Disclosure of Interest T. Takeuchi Grant/research support from: AbbVie GK, Asahi Kasei Pharma, Astellas Pharma, AYUMI Pharmaceutical, Bristol-Myers KK, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical, Teijin Pharma, Consultant for: AbbVie GK, Asahi Kasei Medical, Astellas Pharma, AstraZeneca KK, Bristol-Myers KK, Daiichi Sankyo, Eli Lilly Japan, Janssen Pharmaceutical KK, Merck Serono, Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis Pharma KK, Takeda Pharmaceutical, Speakers bureau: AbbVie GK, Astellas Pharma, Bristol-Myers KK, Celtrion, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Nippon Kayaku, Pfizer Japan, Takeda Pharmaceutical, N. Miyasaka: None declared, T. Inui Employee of: Mitsubishi Tanabe Pharma, T. Yano Employee of: Mitsubishi Tanabe Pharma, T. Yoshinari Employee of: Mitsubishi Tanabe Pharma, T. Abe: None declared, T. Koike Consultant for: Eli Lilly Japan, Pfizer Japan, Speakers bureau: AbbVie GK, Astellas Pharma, Bristol-Myers KK, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Santen Pharmaceutical, Teijin Pharma, UCB Japan

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