Japanese Studies

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 77493 Experts worldwide ranked by ideXlab platform

Regina Kurrasch - One of the best experts on this subject based on the ideXlab platform.

  • sat0166 an analysis of laboratory results from 2 randomized double blind Studies of sirukumab in patients with active rheumatoid arthritis refractory to disease modifying anti rheumatic drug treatment
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: George Karpouzas, Carter Thorne, Stephen Xu, Weichun Xu, Masayoshi Harigai, Yoshiya Tanaka, H Yamanaka, S. Sheng, T. Takeuchi, Regina Kurrasch
    Abstract:

    Background Agents intercepting the IL-6 pathway have been associated with abnormalities in liver enzymes, neutrophils, and platelets. Objectives To evaluate laboratory results from 2 Phase 3 Studies (1 global, 1 Japanese) of sirukumab, a selective human anti-IL6 monoclonal antibody, in patients with active rheumatoid arthritis (RA), and to compare patients using concomitant methotrexate (MTX) or not. Methods In the global study, patients with active RA and inadequate response to disease-modifying anti-rheumatic drugs were randomly assigned (1:1:1) to sirukumab SC 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Approximately 86% were taking MTX at baseline in the global study. In the Japanese study, 122 patients with active RA refractory to MTX or sulfasalazine were assigned (1:1) to monotherapy with sirukumab SC 50mg q4w or sirukumab SC 100mg q2w. Descriptive hematology and chemistry results through Wk 24 were summarized for the 2 sirukumab dose groups, and results were stratified by MTX use. No inferential statistical testing was conducted. Results As has been observed with other IL-6 pathway inhibitors, sirukumab was associated with increases in alanine transaminase (ALT) and aspartate transaminase (AST) and decreases in neutrophil and platelets. The proportion of patients with maximum toxicity grade >1 at Wk 24 for lab results of interest were similar across the sirukumab dose groups (Table). The proportion with increased ALT and AST grade ≥2 (>3x Upper Limit of Normal) through Wk 24 was numerically greater for patients on concomitant MTX in the global study vs those not on MTX. Similarly, continued MTX exposure numerically amplified the effect of sirukumab treatment on liver test abnormalities in the 121 Japanese patients in the global study (on MTX), vs the Japanese monotherapy study. Neutrophil and platelet decreases were similar between groups with and without MTX. Conclusions Numeric differences in abnormally elevated liver enzyme tests for RA patients treated with sirukumab were observed between patients on MTX and not on MTX, including patients from the global and Japanese Studies. In these 2 Phase 3 Studies, there was no clear dose-dependent effect on ALT, AST, neutrophils, or platelets between the 2 sirukumab doses. Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, H. Yamanaka Grant/research support from: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Mitsubishi-Tanabe, Takeda, UCB, Consultant for: Teijin Pharma, Bristol-Meyers, AbbVie, M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, T. Ota Employee of: Janssen Pharmaceutical K.K., S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC

  • sat0166 an analysis of laboratory results from 2 randomized double blind Studies of sirukumab in patients with active rheumatoid arthritis refractory to disease modifying anti rheumatic drug treatment
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: George Karpouzas, Carter Thorne, Stephen Xu, Weichun Xu, Masayoshi Harigai, Yoshiya Tanaka, H Yamanaka, S. Sheng, T. Takeuchi, Regina Kurrasch
    Abstract:

    Background Agents intercepting the IL-6 pathway have been associated with abnormalities in liver enzymes, neutrophils, and platelets. Objectives To evaluate laboratory results from 2 Phase 3 Studies (1 global, 1 Japanese) of sirukumab, a selective human anti-IL6 monoclonal antibody, in patients with active rheumatoid arthritis (RA), and to compare patients using concomitant methotrexate (MTX) or not. Methods In the global study, patients with active RA and inadequate response to disease-modifying anti-rheumatic drugs were randomly assigned (1:1:1) to sirukumab SC 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Approximately 86% were taking MTX at baseline in the global study. In the Japanese study, 122 patients with active RA refractory to MTX or sulfasalazine were assigned (1:1) to monotherapy with sirukumab SC 50mg q4w or sirukumab SC 100mg q2w. Descriptive hematology and chemistry results through Wk 24 were summarized for the 2 sirukumab dose groups, and results were stratified by MTX use. No inferential statistical testing was conducted. Results As has been observed with other IL-6 pathway inhibitors, sirukumab was associated with increases in alanine transaminase (ALT) and aspartate transaminase (AST) and decreases in neutrophil and platelets. The proportion of patients with maximum toxicity grade >1 at Wk 24 for lab results of interest were similar across the sirukumab dose groups (Table). The proportion with increased ALT and AST grade ≥2 (>3x Upper Limit of Normal) through Wk 24 was numerically greater for patients on concomitant MTX in the global study vs those not on MTX. Similarly, continued MTX exposure numerically amplified the effect of sirukumab treatment on liver test abnormalities in the 121 Japanese patients in the global study (on MTX), vs the Japanese monotherapy study. Neutrophil and platelet decreases were similar between groups with and without MTX. Conclusions Numeric differences in abnormally elevated liver enzyme tests for RA patients treated with sirukumab were observed between patients on MTX and not on MTX, including patients from the global and Japanese Studies. In these 2 Phase 3 Studies, there was no clear dose-dependent effect on ALT, AST, neutrophils, or platelets between the 2 sirukumab doses. Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, H. Yamanaka Grant/research support from: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Mitsubishi-Tanabe, Takeda, UCB, Consultant for: Teijin Pharma, Bristol-Meyers, AbbVie, M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, T. Ota Employee of: Janssen Pharmaceutical K.K., S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC

Edward Giovannucci - One of the best experts on this subject based on the ideXlab platform.

  • coffee consumption and risk of endometrial cancer findings from a large up to date meta analysis
    International Journal of Cancer, 2012
    Co-Authors: Edward Giovannucci
    Abstract:

    Several epidemiological Studies have examined the association between coffee drinking and risk of endometrial cancer. To provide a quantitative assessment of this association, we conducted a meta-analysis of observational Studies published up to October 2011 through a search of MEDLINE and EMBASE databases and the reference lists of retrieved article. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose-response relationships. A total of 16 Studies (10 case-control and six cohort Studies) on coffee intake with 6,628 endometrial cancer cases were included in the meta-analysis. The pooled RR of endometrial cancer for the highest versus lowest categories of coffee intake was 0.71 (95% CI: 0.62-0.81; p for heterogeneity = 0.13). By study design, the pooled RRs were 0.69 (95% CI: 0.55-0.87) for case-control Studies and 0.70 (95% CI: 0.61-0.80) for cohort Studies. By geographic region, the inverse association was stronger for three Japanese Studies (pooled RR = 0.40; 95% CI: 0.25-0.63) than five Studies from USA/Canada (pooled RR = 0.69; 95% CI: 0.60-0.79) or eight Studies from Europe (pooled RR = 0.79; 95% CI: 0.63-0.99). An increment of one cup per day of coffee intake conferred a pooled RR of 0.92 (95% CI: 0.90-0.95). In conclusion, our findings suggest that increased coffee intake is associated with a reduced risk of endometrial cancer, consistently observed for cohort and case-control Studies. More large Studies are needed to determine subgroups to obtain more benefits from coffee drinking in relation to endometrial cancer risk.

  • coffee consumption and risk of colorectal cancer a systematic review and meta analysis of prospective cohort Studies
    International Journal of Cancer, 2009
    Co-Authors: Wei Liu, Edward Giovannucci
    Abstract:

    An inverse association between coffee consumption and the risk of colorectal cancer has been found in several case-control Studies, but such an association was not consistent in prospective cohort Studies. We conducted a systematic meta-analysis of prospective cohort Studies on coffee consumption and colorectal cancer published up to June 2008. We combined relative risks (RR) for colorectal cancer comparing high vs. low categories of coffee consumption using random-effects models. We identified 12 eligible cohort Studies, which included 646,848 participants and 5,403 cases for colorectal cancer. The summarized result of the meta-analysis comparing high- vs. low-consumption categories showed no significant effect of coffee consumption on colorectal cancer risk (RR = 0.91; 95% confidence intervals [CI]: 0.81-1.02). The RR was 0.93 (95% CI: 0.71-1.22) when considering 4 Studies conducted in the United States of America, 0.91 (95% CI: 0.76-1.10) for 5 Studies from Europe, and 0.83 (95% CI: 0.62-1.10) for 3 Japanese Studies. No significant differences by sex and cancer-site were found, but there was a slight suggestion of an inverse association between coffee consumption and colon cancer in women (RR = 0.79; 95% CI: 0.60-1.04), especially Japanese women (RR = 0.62; 95% CI: 0.37-1.05). The suggestive inverse associations were slightly stronger in Studies that controlled for smoking and alcohol, and in Studies with shorter follow-up times. Information on coffee type, its serving size, or brewing method may provide a better understanding of this reassuring result and the real role of coffee on colorectal cancer risk.

  • alcohol one carbon metabolism and colorectal cancer recent insights from molecular Studies
    Journal of Nutrition, 2004
    Co-Authors: Edward Giovannucci
    Abstract:

    : A growing body of evidence implicates alcohol intake as a risk factor for colorectal cancer. Until recently, most of the data were based on epidemiologic data that examined alcohol intake in relation to risk of colorectal neoplasia, but the evidence has now been broadened by recent molecular Studies on mechanisms. In particular, a number of observations strongly support a role for alcohol acting through disruptions in one-carbon metabolism. Excessive alcohol intake is a fairly consistent risk factor for colorectal neoplasia in most Studies, and Studies show much higher risks of colorectal neoplasia in those with high alcohol and low folate than with high alcohol or low folate individually. Interactions between high alcohol-low folate and the MTHFR677TT genotype with risk of colorectal neoplasia suggest that alcohol is acting through its effects on one-carbon metabolism because the combination of high alcohol-low folate and the MTHFR677TT genotype are related to markedly elevated serum levels of homocysteine and to DNA hypomethylation. In addition, in Japanese Studies, consumers of alcohol possessing the ALDH2*2 allele, who have very elevated levels of acetaldehyde, are at high risk for colorectal cancer. The relatively high prevalence of the ALDH2*2 allele may thus account for the stronger association between alcohol and colorectal neoplasia that is frequently observed in Studies in Japanese populations. Further research integrating Studies with more detailed data on alcohol intake levels and patterns, folate and other related nutrient status, and relevant genotypes may help clarify unresolved questions regarding the health consequences of moderate to high alcohol drinking.

Yoshiya Tanaka - One of the best experts on this subject based on the ideXlab platform.

  • sat0166 an analysis of laboratory results from 2 randomized double blind Studies of sirukumab in patients with active rheumatoid arthritis refractory to disease modifying anti rheumatic drug treatment
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: George Karpouzas, Carter Thorne, Stephen Xu, Weichun Xu, Masayoshi Harigai, Yoshiya Tanaka, H Yamanaka, S. Sheng, T. Takeuchi, Regina Kurrasch
    Abstract:

    Background Agents intercepting the IL-6 pathway have been associated with abnormalities in liver enzymes, neutrophils, and platelets. Objectives To evaluate laboratory results from 2 Phase 3 Studies (1 global, 1 Japanese) of sirukumab, a selective human anti-IL6 monoclonal antibody, in patients with active rheumatoid arthritis (RA), and to compare patients using concomitant methotrexate (MTX) or not. Methods In the global study, patients with active RA and inadequate response to disease-modifying anti-rheumatic drugs were randomly assigned (1:1:1) to sirukumab SC 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Approximately 86% were taking MTX at baseline in the global study. In the Japanese study, 122 patients with active RA refractory to MTX or sulfasalazine were assigned (1:1) to monotherapy with sirukumab SC 50mg q4w or sirukumab SC 100mg q2w. Descriptive hematology and chemistry results through Wk 24 were summarized for the 2 sirukumab dose groups, and results were stratified by MTX use. No inferential statistical testing was conducted. Results As has been observed with other IL-6 pathway inhibitors, sirukumab was associated with increases in alanine transaminase (ALT) and aspartate transaminase (AST) and decreases in neutrophil and platelets. The proportion of patients with maximum toxicity grade >1 at Wk 24 for lab results of interest were similar across the sirukumab dose groups (Table). The proportion with increased ALT and AST grade ≥2 (>3x Upper Limit of Normal) through Wk 24 was numerically greater for patients on concomitant MTX in the global study vs those not on MTX. Similarly, continued MTX exposure numerically amplified the effect of sirukumab treatment on liver test abnormalities in the 121 Japanese patients in the global study (on MTX), vs the Japanese monotherapy study. Neutrophil and platelet decreases were similar between groups with and without MTX. Conclusions Numeric differences in abnormally elevated liver enzyme tests for RA patients treated with sirukumab were observed between patients on MTX and not on MTX, including patients from the global and Japanese Studies. In these 2 Phase 3 Studies, there was no clear dose-dependent effect on ALT, AST, neutrophils, or platelets between the 2 sirukumab doses. Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, H. Yamanaka Grant/research support from: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Mitsubishi-Tanabe, Takeda, UCB, Consultant for: Teijin Pharma, Bristol-Meyers, AbbVie, M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, T. Ota Employee of: Janssen Pharmaceutical K.K., S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC

  • sat0166 an analysis of laboratory results from 2 randomized double blind Studies of sirukumab in patients with active rheumatoid arthritis refractory to disease modifying anti rheumatic drug treatment
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: George Karpouzas, Carter Thorne, Stephen Xu, Weichun Xu, Masayoshi Harigai, Yoshiya Tanaka, H Yamanaka, S. Sheng, T. Takeuchi, Regina Kurrasch
    Abstract:

    Background Agents intercepting the IL-6 pathway have been associated with abnormalities in liver enzymes, neutrophils, and platelets. Objectives To evaluate laboratory results from 2 Phase 3 Studies (1 global, 1 Japanese) of sirukumab, a selective human anti-IL6 monoclonal antibody, in patients with active rheumatoid arthritis (RA), and to compare patients using concomitant methotrexate (MTX) or not. Methods In the global study, patients with active RA and inadequate response to disease-modifying anti-rheumatic drugs were randomly assigned (1:1:1) to sirukumab SC 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Approximately 86% were taking MTX at baseline in the global study. In the Japanese study, 122 patients with active RA refractory to MTX or sulfasalazine were assigned (1:1) to monotherapy with sirukumab SC 50mg q4w or sirukumab SC 100mg q2w. Descriptive hematology and chemistry results through Wk 24 were summarized for the 2 sirukumab dose groups, and results were stratified by MTX use. No inferential statistical testing was conducted. Results As has been observed with other IL-6 pathway inhibitors, sirukumab was associated with increases in alanine transaminase (ALT) and aspartate transaminase (AST) and decreases in neutrophil and platelets. The proportion of patients with maximum toxicity grade >1 at Wk 24 for lab results of interest were similar across the sirukumab dose groups (Table). The proportion with increased ALT and AST grade ≥2 (>3x Upper Limit of Normal) through Wk 24 was numerically greater for patients on concomitant MTX in the global study vs those not on MTX. Similarly, continued MTX exposure numerically amplified the effect of sirukumab treatment on liver test abnormalities in the 121 Japanese patients in the global study (on MTX), vs the Japanese monotherapy study. Neutrophil and platelet decreases were similar between groups with and without MTX. Conclusions Numeric differences in abnormally elevated liver enzyme tests for RA patients treated with sirukumab were observed between patients on MTX and not on MTX, including patients from the global and Japanese Studies. In these 2 Phase 3 Studies, there was no clear dose-dependent effect on ALT, AST, neutrophils, or platelets between the 2 sirukumab doses. Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, H. Yamanaka Grant/research support from: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Mitsubishi-Tanabe, Takeda, UCB, Consultant for: Teijin Pharma, Bristol-Meyers, AbbVie, M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, T. Ota Employee of: Janssen Pharmaceutical K.K., S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC

  • early response to certolizumab pegol predicts long term outcomes in patients with active rheumatoid arthritis results from the Japanese Studies
    Modern Rheumatology, 2015
    Co-Authors: Tsutomu Takeuchi, Yoshiya Tanaka, Kazuhiko Yamamoto, Hisashi Yamanaka, Naoki Ishiguro, Katsumi Eguchi, Akira Watanabe, Hideki Origasa, T Shoji, Nobuyuki Miyasaka
    Abstract:

    AbstractObjectives. A post-hoc analysis was performed to determine the relationship between the timing and magnitude of DAS28(ESR) response and long term outcomes in Japanese patients after 1 year of CZP treatment.Methods. Our analysis included 82 J-RAPID trial patients treated with CZP 200 mg and methotrexate, and 116 HIKARI trial patients treated with CZP 200 mg alone or with disease-modifying agents other than methotrexate. Remission rates and changes in mTSS at year 1 were compared to the DAS28(ESR) response at week 12 of CZP treatment.Results. After 1 year of treatment, remission was achieved in 41.3% of the J-RAPID and 34.9% of the HIKARI patients with a week 12 DAS28(ESR) response of ≥ 1.2. In comparison, patients with a DAS28(ESR) response of < 1.2 at week 12 only had a < 7% probability of achieving remission and displayed higher change in mTSS after 1-year treatment.Conclusions. The likelihood of remission and extent of radiographic progression after 1 year was associated with the week 12 DAS28(E...

George Karpouzas - One of the best experts on this subject based on the ideXlab platform.

  • sat0166 an analysis of laboratory results from 2 randomized double blind Studies of sirukumab in patients with active rheumatoid arthritis refractory to disease modifying anti rheumatic drug treatment
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: George Karpouzas, Carter Thorne, Stephen Xu, Weichun Xu, Masayoshi Harigai, Yoshiya Tanaka, H Yamanaka, S. Sheng, T. Takeuchi, Regina Kurrasch
    Abstract:

    Background Agents intercepting the IL-6 pathway have been associated with abnormalities in liver enzymes, neutrophils, and platelets. Objectives To evaluate laboratory results from 2 Phase 3 Studies (1 global, 1 Japanese) of sirukumab, a selective human anti-IL6 monoclonal antibody, in patients with active rheumatoid arthritis (RA), and to compare patients using concomitant methotrexate (MTX) or not. Methods In the global study, patients with active RA and inadequate response to disease-modifying anti-rheumatic drugs were randomly assigned (1:1:1) to sirukumab SC 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Approximately 86% were taking MTX at baseline in the global study. In the Japanese study, 122 patients with active RA refractory to MTX or sulfasalazine were assigned (1:1) to monotherapy with sirukumab SC 50mg q4w or sirukumab SC 100mg q2w. Descriptive hematology and chemistry results through Wk 24 were summarized for the 2 sirukumab dose groups, and results were stratified by MTX use. No inferential statistical testing was conducted. Results As has been observed with other IL-6 pathway inhibitors, sirukumab was associated with increases in alanine transaminase (ALT) and aspartate transaminase (AST) and decreases in neutrophil and platelets. The proportion of patients with maximum toxicity grade >1 at Wk 24 for lab results of interest were similar across the sirukumab dose groups (Table). The proportion with increased ALT and AST grade ≥2 (>3x Upper Limit of Normal) through Wk 24 was numerically greater for patients on concomitant MTX in the global study vs those not on MTX. Similarly, continued MTX exposure numerically amplified the effect of sirukumab treatment on liver test abnormalities in the 121 Japanese patients in the global study (on MTX), vs the Japanese monotherapy study. Neutrophil and platelet decreases were similar between groups with and without MTX. Conclusions Numeric differences in abnormally elevated liver enzyme tests for RA patients treated with sirukumab were observed between patients on MTX and not on MTX, including patients from the global and Japanese Studies. In these 2 Phase 3 Studies, there was no clear dose-dependent effect on ALT, AST, neutrophils, or platelets between the 2 sirukumab doses. Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, H. Yamanaka Grant/research support from: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Mitsubishi-Tanabe, Takeda, UCB, Consultant for: Teijin Pharma, Bristol-Meyers, AbbVie, M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, T. Ota Employee of: Janssen Pharmaceutical K.K., S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC

  • sat0166 an analysis of laboratory results from 2 randomized double blind Studies of sirukumab in patients with active rheumatoid arthritis refractory to disease modifying anti rheumatic drug treatment
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: George Karpouzas, Carter Thorne, Stephen Xu, Weichun Xu, Masayoshi Harigai, Yoshiya Tanaka, H Yamanaka, S. Sheng, T. Takeuchi, Regina Kurrasch
    Abstract:

    Background Agents intercepting the IL-6 pathway have been associated with abnormalities in liver enzymes, neutrophils, and platelets. Objectives To evaluate laboratory results from 2 Phase 3 Studies (1 global, 1 Japanese) of sirukumab, a selective human anti-IL6 monoclonal antibody, in patients with active rheumatoid arthritis (RA), and to compare patients using concomitant methotrexate (MTX) or not. Methods In the global study, patients with active RA and inadequate response to disease-modifying anti-rheumatic drugs were randomly assigned (1:1:1) to sirukumab SC 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Approximately 86% were taking MTX at baseline in the global study. In the Japanese study, 122 patients with active RA refractory to MTX or sulfasalazine were assigned (1:1) to monotherapy with sirukumab SC 50mg q4w or sirukumab SC 100mg q2w. Descriptive hematology and chemistry results through Wk 24 were summarized for the 2 sirukumab dose groups, and results were stratified by MTX use. No inferential statistical testing was conducted. Results As has been observed with other IL-6 pathway inhibitors, sirukumab was associated with increases in alanine transaminase (ALT) and aspartate transaminase (AST) and decreases in neutrophil and platelets. The proportion of patients with maximum toxicity grade >1 at Wk 24 for lab results of interest were similar across the sirukumab dose groups (Table). The proportion with increased ALT and AST grade ≥2 (>3x Upper Limit of Normal) through Wk 24 was numerically greater for patients on concomitant MTX in the global study vs those not on MTX. Similarly, continued MTX exposure numerically amplified the effect of sirukumab treatment on liver test abnormalities in the 121 Japanese patients in the global study (on MTX), vs the Japanese monotherapy study. Neutrophil and platelet decreases were similar between groups with and without MTX. Conclusions Numeric differences in abnormally elevated liver enzyme tests for RA patients treated with sirukumab were observed between patients on MTX and not on MTX, including patients from the global and Japanese Studies. In these 2 Phase 3 Studies, there was no clear dose-dependent effect on ALT, AST, neutrophils, or platelets between the 2 sirukumab doses. Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, H. Yamanaka Grant/research support from: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Mitsubishi-Tanabe, Takeda, UCB, Consultant for: Teijin Pharma, Bristol-Meyers, AbbVie, M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, T. Ota Employee of: Janssen Pharmaceutical K.K., S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC

Masayoshi Harigai - One of the best experts on this subject based on the ideXlab platform.

  • sat0166 an analysis of laboratory results from 2 randomized double blind Studies of sirukumab in patients with active rheumatoid arthritis refractory to disease modifying anti rheumatic drug treatment
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: George Karpouzas, Carter Thorne, Stephen Xu, Weichun Xu, Masayoshi Harigai, Yoshiya Tanaka, H Yamanaka, S. Sheng, T. Takeuchi, Regina Kurrasch
    Abstract:

    Background Agents intercepting the IL-6 pathway have been associated with abnormalities in liver enzymes, neutrophils, and platelets. Objectives To evaluate laboratory results from 2 Phase 3 Studies (1 global, 1 Japanese) of sirukumab, a selective human anti-IL6 monoclonal antibody, in patients with active rheumatoid arthritis (RA), and to compare patients using concomitant methotrexate (MTX) or not. Methods In the global study, patients with active RA and inadequate response to disease-modifying anti-rheumatic drugs were randomly assigned (1:1:1) to sirukumab SC 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Approximately 86% were taking MTX at baseline in the global study. In the Japanese study, 122 patients with active RA refractory to MTX or sulfasalazine were assigned (1:1) to monotherapy with sirukumab SC 50mg q4w or sirukumab SC 100mg q2w. Descriptive hematology and chemistry results through Wk 24 were summarized for the 2 sirukumab dose groups, and results were stratified by MTX use. No inferential statistical testing was conducted. Results As has been observed with other IL-6 pathway inhibitors, sirukumab was associated with increases in alanine transaminase (ALT) and aspartate transaminase (AST) and decreases in neutrophil and platelets. The proportion of patients with maximum toxicity grade >1 at Wk 24 for lab results of interest were similar across the sirukumab dose groups (Table). The proportion with increased ALT and AST grade ≥2 (>3x Upper Limit of Normal) through Wk 24 was numerically greater for patients on concomitant MTX in the global study vs those not on MTX. Similarly, continued MTX exposure numerically amplified the effect of sirukumab treatment on liver test abnormalities in the 121 Japanese patients in the global study (on MTX), vs the Japanese monotherapy study. Neutrophil and platelet decreases were similar between groups with and without MTX. Conclusions Numeric differences in abnormally elevated liver enzyme tests for RA patients treated with sirukumab were observed between patients on MTX and not on MTX, including patients from the global and Japanese Studies. In these 2 Phase 3 Studies, there was no clear dose-dependent effect on ALT, AST, neutrophils, or platelets between the 2 sirukumab doses. Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, H. Yamanaka Grant/research support from: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Mitsubishi-Tanabe, Takeda, UCB, Consultant for: Teijin Pharma, Bristol-Meyers, AbbVie, M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, T. Ota Employee of: Janssen Pharmaceutical K.K., S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC

  • sat0166 an analysis of laboratory results from 2 randomized double blind Studies of sirukumab in patients with active rheumatoid arthritis refractory to disease modifying anti rheumatic drug treatment
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: George Karpouzas, Carter Thorne, Stephen Xu, Weichun Xu, Masayoshi Harigai, Yoshiya Tanaka, H Yamanaka, S. Sheng, T. Takeuchi, Regina Kurrasch
    Abstract:

    Background Agents intercepting the IL-6 pathway have been associated with abnormalities in liver enzymes, neutrophils, and platelets. Objectives To evaluate laboratory results from 2 Phase 3 Studies (1 global, 1 Japanese) of sirukumab, a selective human anti-IL6 monoclonal antibody, in patients with active rheumatoid arthritis (RA), and to compare patients using concomitant methotrexate (MTX) or not. Methods In the global study, patients with active RA and inadequate response to disease-modifying anti-rheumatic drugs were randomly assigned (1:1:1) to sirukumab SC 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Approximately 86% were taking MTX at baseline in the global study. In the Japanese study, 122 patients with active RA refractory to MTX or sulfasalazine were assigned (1:1) to monotherapy with sirukumab SC 50mg q4w or sirukumab SC 100mg q2w. Descriptive hematology and chemistry results through Wk 24 were summarized for the 2 sirukumab dose groups, and results were stratified by MTX use. No inferential statistical testing was conducted. Results As has been observed with other IL-6 pathway inhibitors, sirukumab was associated with increases in alanine transaminase (ALT) and aspartate transaminase (AST) and decreases in neutrophil and platelets. The proportion of patients with maximum toxicity grade >1 at Wk 24 for lab results of interest were similar across the sirukumab dose groups (Table). The proportion with increased ALT and AST grade ≥2 (>3x Upper Limit of Normal) through Wk 24 was numerically greater for patients on concomitant MTX in the global study vs those not on MTX. Similarly, continued MTX exposure numerically amplified the effect of sirukumab treatment on liver test abnormalities in the 121 Japanese patients in the global study (on MTX), vs the Japanese monotherapy study. Neutrophil and platelet decreases were similar between groups with and without MTX. Conclusions Numeric differences in abnormally elevated liver enzyme tests for RA patients treated with sirukumab were observed between patients on MTX and not on MTX, including patients from the global and Japanese Studies. In these 2 Phase 3 Studies, there was no clear dose-dependent effect on ALT, AST, neutrophils, or platelets between the 2 sirukumab doses. Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, H. Yamanaka Grant/research support from: Teijin Pharma, Chugai, Astellas, Bristol-Meyers, AbbVie, Daiichi-Sankyo, Mitsubishi-Tanabe, Takeda, UCB, Consultant for: Teijin Pharma, Bristol-Meyers, AbbVie, M. Harigai Grant/research support from: Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and UCB Japan, T. Ota Employee of: Janssen Pharmaceutical K.K., S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC

Japanese Studies - 15 days free trial to Access Experts & Abstracts