Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Clinical Efficacy of Infliximab Is Maximized When Both Circulating TNF and IL-6 Are Suppressed In the Treatment of Rheumatoid ArthritisResults From the RISING Study.

Takeuchi1,  Tsutomu, Tatsuki2,  Yoshihiko, Yano2,  Toshiro, Yoshinari2,  Toru, Miyasaka3,  Nobuyuki, Abe4,  Tohru, Koike5,  Takao

School of Medicine, Keio University, Tokyo, Japan
Mitsubishi Tanabe Pharma Corporation, Osaka, Japan
Tokyo Med & Dent Univ, Tokyo, Japan
Saitama Medical School, Kawagoe-shi Saitama, Japan
Sapporo Medical Center NTT EC, Sapporo, Japan


We have previously reported the practicability of the dose escalation of infliximab (IFX), an anti-TNF antibody, in MTX-refractory patients with rheumatoid arthritis (RA) in the RISING study (NCT00691028)*. Here, we show the analysis of the clinical response from the viewpoints of serum IFX level and plasma IL-6 level.


After the patients with RA refractory to MTX received 3 mg/kg IFX infusion at weeks 0, 2, and 6, they were randomly assigned for the administration of 3, 6, or 10 mg/kg IFX, every 8 weeks from week 14 to 46 in a double-blind manner (n=307). Disease activity was evaluated at week 54 by using DAS28-ESR or SDAI. Serum IFX and plasma IL-6 levels were measured by ELISA. Because the circulating TNF level could not be measured correctly in the presence of IFX, we used IFX level as the surrogate marker of the TNF level. For an index in TNF and IL-6 level, we stratified all patients who had complete data at week 54 (disease activity, IFX level and IL-6 level, n=271) into four groups: Group-1 (IFX-high/IL-6-low: suppression seen in both TNF and IL-6); Group-2 (IFX-high/IL-6-high: suppression in TNF only); Group-3 (IFX-low/IL6-low: suppression in IL-6 only); Group-4 (IFX-low/IL6-high: neither TNF nor IL-6 were suppressed). The cut-off values of IFX and IL-6 levels were determined as <1 mg/ml (the threshold level for clinical response of IFX) and <10 pg/ml (below the third quartile at week 54).


Immediately after starting IFX treatment, the IL-6 level was markedly decreased. Median (IQR) IL-6 level at baseline (week 0) and at week 54 were 28.9 (12.8, 65.0) and 2.4 (0.9, 16.3) pg/ml, respectively, and the median reduction rate was 87%. IFX level closely and negatively correlated with the IL-6 level (rho=-0.58, p<0.001). Both IFX and IL-6 levels were closely correlated with disease activity as well as various components such as tender/swollen joint counts and patient global assessment. The number of patients in Group-1, 2, 3 and 4 were 134, 31, 48, and 58, and approximately half of the patients were in Group-1 (both TNF and IL-6 were suppressed). There is a significant difference in the clinical responses among Groups-1, 2, 3 and 4, and Group-1 exhibited the highest clinical response, especially clinical remission. Meanwhile, Group-4 (neither TNF nor IL-6 were suppressed) showed the lowest rate of response. Clinical response in Group-2 and Group-3 were intermediate values between those of Group-1 and Group-4 (Fig.). Similar results were obtained in the other components of disease activity.


IFX therapy remarkably suppressed not only TNF, but also the IL-6 level in RA patients. The clinical efficacy of IFX therapy was maximized when both circulating TNF and IL-6 were suppressed by the treatment.

*Takeuchi, T, et al. Mod Rheumatol 2009;19:478.

To cite this abstract, please use the following information:
Takeuchi, Tsutomu, Tatsuki, Yoshihiko, Yano, Toshiro, Yoshinari, Toru, Miyasaka, Nobuyuki, Abe, Tohru, et al; Clinical Efficacy of Infliximab Is Maximized When Both Circulating TNF and IL-6 Are Suppressed In the Treatment of Rheumatoid ArthritisResults From the RISING Study. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2188

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