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1. Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions:an update

Author

Aletaha, Daniel, Kerschbaumer, Andreas, Kastrati, Kastriot, Dejaco, Christian, Dougados, Maxime, McInnes, Iain B., Sattar, Naveed, Stamm, Tanja A., Takeuchi, Tsutomu, Trauner, Michael, Van Der Heijde, Désirée, Voshaar, Marieke, Winthrop, Kevin L., Ravelli, Angelo, Betteridge, Neil, Burmester, Gerd Rüdiger R., Bijlsma, Johannes W.J., Bykerk, Vivian, Caporali, Roberto, Choy, Ernest H., Codreanu, Catalin, Combe, Bernard, Crow, Mary K., De Wit, Maarten, Emery, Paul, Fleischmann, Roy M., Gabay, Cem, Hetland, Merete Lund, Hyrich, Kimme L., Iagnocco, Annamaria, Isaacs, John D., Kremer, Joel M., Mariette, Xavier, Merkel, Peter, Mysler, Eduardo F., Nash, Peter, Nurmohamed, Michael T., Pavelka, Karel, Poor, Gyula, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Strangfeld, Anja, Tanaka, Yoshiya, Smolen, Josef S., Aletaha, Daniel, Kerschbaumer, Andreas, Kastrati, Kastriot, Dejaco, Christian, Dougados, Maxime, McInnes, Iain B., Sattar, Naveed, Stamm, Tanja A., Takeuchi, Tsutomu, Trauner, Michael, Van Der Heijde, Désirée, Voshaar, Marieke, Winthrop, Kevin L., Ravelli, Angelo, Betteridge, Neil, Burmester, Gerd Rüdiger R., Bijlsma, Johannes W.J., Bykerk, Vivian, Caporali, Roberto, Choy, Ernest H., Codreanu, Catalin, Combe, Bernard, Crow, Mary K., De Wit, Maarten, Emery, Paul, Fleischmann, Roy M., Gabay, Cem, Hetland, Merete Lund, Hyrich, Kimme L., Iagnocco, Annamaria, Isaacs, John D., Kremer, Joel M., Mariette, Xavier, Merkel, Peter, Mysler, Eduardo F., Nash, Peter, Nurmohamed, Michael T., Pavelka, Karel, Poor, Gyula, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Strangfeld, Anja, Tanaka, Yoshiya, and Smolen, Josef S.

Published
2023

2. Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update

Author

MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Aletaha, Daniel, Kerschbaumer, Andreas, Kastrati, Kastriot, Dejaco, Christian, Dougados, Maxime, McInnes, Iain B., Sattar, Naveed, Stamm, Tanja A., Takeuchi, Tsutomu, Trauner, Michael, Van Der Heijde, Désirée, Voshaar, Marieke, Winthrop, Kevin L., Ravelli, Angelo, Betteridge, Neil, Burmester, Gerd Rüdiger R., Bijlsma, Johannes W.J., Bykerk, Vivian, Caporali, Roberto, Choy, Ernest H., Codreanu, Catalin, Combe, Bernard, Crow, Mary K., De Wit, Maarten, Emery, Paul, Fleischmann, Roy M., Gabay, Cem, Hetland, Merete Lund, Hyrich, Kimme L., Iagnocco, Annamaria, Isaacs, John D., Kremer, Joel M., Mariette, Xavier, Merkel, Peter A., Mysler, Eduardo F., Nash, Peter, Nurmohamed, Michael T., Pavelka, Karel, Poor, Gyula, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Strangfeld, Anja, Tanaka, Yoshiya, Smolen, Josef S., MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Aletaha, Daniel, Kerschbaumer, Andreas, Kastrati, Kastriot, Dejaco, Christian, Dougados, Maxime, McInnes, Iain B., Sattar, Naveed, Stamm, Tanja A., Takeuchi, Tsutomu, Trauner, Michael, Van Der Heijde, Désirée, Voshaar, Marieke, Winthrop, Kevin L., Ravelli, Angelo, Betteridge, Neil, Burmester, Gerd Rüdiger R., Bijlsma, Johannes W.J., Bykerk, Vivian, Caporali, Roberto, Choy, Ernest H., Codreanu, Catalin, Combe, Bernard, Crow, Mary K., De Wit, Maarten, Emery, Paul, Fleischmann, Roy M., Gabay, Cem, Hetland, Merete Lund, Hyrich, Kimme L., Iagnocco, Annamaria, Isaacs, John D., Kremer, Joel M., Mariette, Xavier, Merkel, Peter A., Mysler, Eduardo F., Nash, Peter, Nurmohamed, Michael T., Pavelka, Karel, Poor, Gyula, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Strangfeld, Anja, Tanaka, Yoshiya, and Smolen, Josef S.

Published
2023

3. Disease activity and biologic use in patients with psoriatic arthritis or rheumatoid arthritis.

Author

Kavanaugh, Arthur, Kavanaugh, Arthur, Singh, Rakesh, Karki, Chitra, Etzel, Carol J, Kremer, Joel M, Greenberg, Jeffrey D, Griffith, Jenny, Kavanaugh, Arthur, Kavanaugh, Arthur, Singh, Rakesh, Karki, Chitra, Etzel, Carol J, Kremer, Joel M, Greenberg, Jeffrey D, and Griffith, Jenny

Abstract

To compare disease burden and biologic use among psoriatic arthritis (PsA) or rheumatoid arthritis (RA) patients recruited to the Corrona registry. Retrospective study of patients with PsA or RA enrolled in Corrona between January 2002 and March 2013 and grouped in 2-year intervals. Clinical outcomes and biologic use were assessed. Biologic use increased over time in both cohorts, with 62 and 52% of patients with PsA and RA, respectively, receiving biologics by 2012-2013. However, 25 and 35% of patients with PsA and RA, respectively, continued to experience moderate/high disease activity. Overall, the progressive increase in biologic use accompanied progressive decreases in Clinical Disease Activity Index (from 14.2 to 10.4 for RA, and 12.4 to 8.1 for PsA) and mean Health Assessment Questionnaire score (from 0.36 to 0.34, and 0.3 to 0.24). Mean patient pain, the proportion of patients reporting morning stiffness, and the mean duration of morning stiffness remained similar for both cohorts. PsA and RA treated in the rheumatology setting had a comparable impact on patient quality of life and functional ability. Disease burden improved with increased biologic utilization in both groups; however, moderate/severe disease remains in a significant proportion of PsA and RA patients.

Published
2018

4. Disease activity and biologic use in patients with psoriatic arthritis or rheumatoid arthritis.

Author

Kavanaugh, Arthur, Kavanaugh, Arthur, Singh, Rakesh, Karki, Chitra, Etzel, Carol J, Kremer, Joel M, Greenberg, Jeffrey D, Griffith, Jenny, Kavanaugh, Arthur, Kavanaugh, Arthur, Singh, Rakesh, Karki, Chitra, Etzel, Carol J, Kremer, Joel M, Greenberg, Jeffrey D, and Griffith, Jenny

Abstract

To compare disease burden and biologic use among psoriatic arthritis (PsA) or rheumatoid arthritis (RA) patients recruited to the Corrona registry. Retrospective study of patients with PsA or RA enrolled in Corrona between January 2002 and March 2013 and grouped in 2-year intervals. Clinical outcomes and biologic use were assessed. Biologic use increased over time in both cohorts, with 62 and 52% of patients with PsA and RA, respectively, receiving biologics by 2012-2013. However, 25 and 35% of patients with PsA and RA, respectively, continued to experience moderate/high disease activity. Overall, the progressive increase in biologic use accompanied progressive decreases in Clinical Disease Activity Index (from 14.2 to 10.4 for RA, and 12.4 to 8.1 for PsA) and mean Health Assessment Questionnaire score (from 0.36 to 0.34, and 0.3 to 0.24). Mean patient pain, the proportion of patients reporting morning stiffness, and the mean duration of morning stiffness remained similar for both cohorts. PsA and RA treated in the rheumatology setting had a comparable impact on patient quality of life and functional ability. Disease burden improved with increased biologic utilization in both groups; however, moderate/severe disease remains in a significant proportion of PsA and RA patients.

Published
2018

5. Sex differences in gout characteristics: tailoring care for women and men.

Author

Harrold, Leslie R, Harrold, Leslie R, Etzel, Carol J, Gibofsky, Allan, Kremer, Joel M, Pillinger, Michael H, Saag, Kenneth G, Schlesinger, Naomi, Terkeltaub, Robert, Cox, Vanessa, Greenberg, Jeffrey D, Harrold, Leslie R, Harrold, Leslie R, Etzel, Carol J, Gibofsky, Allan, Kremer, Joel M, Pillinger, Michael H, Saag, Kenneth G, Schlesinger, Naomi, Terkeltaub, Robert, Cox, Vanessa, and Greenberg, Jeffrey D

Abstract

BackgroundTo characterize the differences between women and men with gout.MethodsWe analyzed a US national cohort of gout patients cared for by rheumatologists.ResultsCompared with the 1012 men with gout, women with gout (n = 262) were older (71 vs. 61 years, p < 0.001) and had a greater burden of comorbid conditions (p < 0.001 for hypertension, diabetes, renal disease and obesity). Risk factors for gout differed with women more often taking diuretics (p < 0.001), while men more frequently had dietary triggers (p < 0.05).ConclusionsThe profiles of women and men with gout are markedly different, suggesting a need to tailor treatment recommendations.

Published
2017

6. Sex differences in gout characteristics: tailoring care for women and men.

Author

Harrold, Leslie R, Harrold, Leslie R, Etzel, Carol J, Gibofsky, Allan, Kremer, Joel M, Pillinger, Michael H, Saag, Kenneth G, Schlesinger, Naomi, Terkeltaub, Robert, Cox, Vanessa, Greenberg, Jeffrey D, Harrold, Leslie R, Harrold, Leslie R, Etzel, Carol J, Gibofsky, Allan, Kremer, Joel M, Pillinger, Michael H, Saag, Kenneth G, Schlesinger, Naomi, Terkeltaub, Robert, Cox, Vanessa, and Greenberg, Jeffrey D

Abstract

BackgroundTo characterize the differences between women and men with gout.MethodsWe analyzed a US national cohort of gout patients cared for by rheumatologists.ResultsCompared with the 1012 men with gout, women with gout (n = 262) were older (71 vs. 61 years, p < 0.001) and had a greater burden of comorbid conditions (p < 0.001 for hypertension, diabetes, renal disease and obesity). Risk factors for gout differed with women more often taking diuretics (p < 0.001), while men more frequently had dietary triggers (p < 0.05).ConclusionsThe profiles of women and men with gout are markedly different, suggesting a need to tailor treatment recommendations.

Published
2017

7. Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Author

Nishikawa, Masataka, Owaki, Hajime, Fuji, Takeshi, Soliman, Moetaza M., Ashcroft, Darren M., Watson, Kath D., Lunt, Mark, Symmons, Deborah, Hyrich, Kimme L., Atkinson, Francesca, Malik, Saadia, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Hamilton, Jennifer, Kelly, Clive, Burmester, Gerd, Kary, Sonja, Unnebrink, Kristina, Guérette, Benoit, Oezer, Uemit, Kupper, Hartmut, Dennison, Elaine, Jameson, Karen, Hyrich, Kimme, Watson, Kath, Landewe, Robert, Keystone, Edward, Smolen, Josef, Goldring, Mary, Patra, Kaushik, Cifaldi, Mary, van der Heijde, Désirée, Lloyd, Lois A., Owen, Catherine, Breslin, Anne, Ahmad, Yasmeen, Emery, Paul, Matteson, E. L., Genovese, M., Sague, S., Hsia, E. C., Doyle, M. K., Fan, H., Elashoff, M., Kirkham, Bruce, Wasco, M. C., Bathon, J., Fleischmann, R., Genovese, M. C., Liu, H., Goldman, J., Leirisalo-Repo, M., Zanetakis, E., El-Kadi, H., Kellner, H., Bolce, R., Wang, J., Dehoratius, R., Decktor, D., Kremer, J., Taylor, Peter, Mendelsohn, A., Baker, D., Kim, L., Ritchlin, C., Mariette, Xavier, Matucci Cerenic, Marco, Pavelka, Karel, van Vollenhoven, Ronald, Heatley, Rebecca, Walsh, Claire, Lawson, Richard, Reynolds, Alan, Iaremenko, Oleg, Mikitenko, Ganna, Kavanaugh, Arthur, Luijtens, Kristel, Curtis, Jeffrey, Schiff, Michael, Kvien, Tore, Khanna, Dinesh, Furst, Dan, Behrens, Frank, Koehm, Michaela, Scharbatke, Eva C., Kleinert, Stefan, Weyer, Gerd, Tony, Hans-Peter, Burkhardt, Harald, Blunn, Karina J., Williams, Richard B., Young, Adam, McDowell, Jackie, Weinblatt, Michael, Haraoui, Boulos, Mozaffarian, Neelufar, Khraishi, Majed, Alten, Rieke, Gomez-Reino, Juan, Rizzo, Warren, Schechtman, Joy, Kahan, Andre, Vernon, Emma, Taylor, Monet, Hogan, Vanessa, Holweg, Cecile, Kummerfeld, Sarah, Teng, Onno, Townsend, Michael, van Laar, Jacob M., Gullick, Nicola J., De Silva, Chulanie, Kirkham, Bruce W., Roy, Sanjoy, Emery, P., van der Heijde, D., Keystone, E., Conaghan, P. G., Xu, W., Baratelle, A., Beutler, A., Rahman, M. U., Nikiphorou, Elena, Kiely, Patrick, Walsh, David A., Williams, Richard, Shah, Devron, Knight, Gregory D., Hutchinson, David G., Dass, Shouvik, Atzeni, Fabiola, Vital, Edward M., Bingham, Sarah J., Buch, Maya, Beirne, Paul, Fleischmann, Roy, Dougados, Maxime, Williams, Sarah, Reynard, Mark, Blackler, Laura, Zain, Amir, Oakley, Stephen, Rees, Jonathon, Jones, Tim, Mistlin, Alan, Panayi, Gabriel, Westhovens, Rene, Durez, Patrick, Genant, Harry, Robles, Manuel, Becker, Jean-Claude, Covucci, Allison, Bathon, Joan, Genovese, Mark C., Luggen, Michael, Le Bars, Manuela, Aranda, Richard, Li, Tracy, Elegbe, Ayanbola, Fichtner, Andreas, Strand, Vibeke, Vencovsky, Jiri, Davies, Rebecca, Galloway, James, Hochberg, Marc, Kelly, Sheila, Khan, Nadar, Qi, Keqin, Pappu, Ramesh, Delaet, Ingrid, Luo, Allison, Torbeyns, Anne, Moreland, Larry, Cohen, Roger, Gujrathi, Sheila, Bykerk, Vivian P., Álvaro-Gracia, Jose, Andres Roman Ivorra, Jose, Nurmohamed, Michael T., Bernasconi, Corrado, Stancati, Andrea, Sibilia, Jean, Östör, Andrew, Strangfeld, Anja, Eveslage, Maria, Listing, Joachim, Herzer, Peter, Liebhaber, Anke, Krummel-Lorenz, Brigitte, Zink, Angela, Breedveld, Ferdinand C., Cohen, Stanley B., Matteson, Eric L., Burke, Laura, Chai, Akiko, Reiss, William, Sweetser, Marianne, Shaw, Tim, Ellis, Shawn D., Ehrenstein, Michael R., Notley, Clare A., Yazici, Yusuf, Ince, Akgun, Baraf, Herbert, Malamet, Raymond, Chung, Carol Y., Hughes, Chris, Faurholm, Bjarne, Dell'Accio, Francesco, Manzo, Antonio, Seed, Michael, Eltawil, Noha, Marrelli, Alessandra, Gould, David, Subang, Christina, Al-Kashi, Adam, De Bari, Cosimo, Winyard, Paul, Chernajovsky, Yuti, Nissim, Ahuva, Bingham, Clifton, Fleischmann, Roy M., Furst, Daniel E., Macey, Katherine M., Sweetser, Marianne T., Lehane, Patricia, Farmer, Pamela, Long, Simon G., Kremer, Joel M., Burgos-Vargas, Ruben, Dudler, Jean, Mela, Christopher M., Wegner, Natalia, Lugli, Helena, Quirke, Anne-Marie, Guo, Yonghua, Potempa, Jan, Venables, Patrick, Nishikawa, Masataka, Owaki, Hajime, Fuji, Takeshi, Soliman, Moetaza M., Ashcroft, Darren M., Watson, Kath D., Lunt, Mark, Symmons, Deborah, Hyrich, Kimme L., Atkinson, Francesca, Malik, Saadia, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Hamilton, Jennifer, Kelly, Clive, Burmester, Gerd, Kary, Sonja, Unnebrink, Kristina, Guérette, Benoit, Oezer, Uemit, Kupper, Hartmut, Dennison, Elaine, Jameson, Karen, Hyrich, Kimme, Watson, Kath, Landewe, Robert, Keystone, Edward, Smolen, Josef, Goldring, Mary, Patra, Kaushik, Cifaldi, Mary, van der Heijde, Désirée, Lloyd, Lois A., Owen, Catherine, Breslin, Anne, Ahmad, Yasmeen, Emery, Paul, Matteson, E. L., Genovese, M., Sague, S., Hsia, E. C., Doyle, M. K., Fan, H., Elashoff, M., Kirkham, Bruce, Wasco, M. C., Bathon, J., Fleischmann, R., Genovese, M. C., Liu, H., Goldman, J., Leirisalo-Repo, M., Zanetakis, E., El-Kadi, H., Kellner, H., Bolce, R., Wang, J., Dehoratius, R., Decktor, D., Kremer, J., Taylor, Peter, Mendelsohn, A., Baker, D., Kim, L., Ritchlin, C., Mariette, Xavier, Matucci Cerenic, Marco, Pavelka, Karel, van Vollenhoven, Ronald, Heatley, Rebecca, Walsh, Claire, Lawson, Richard, Reynolds, Alan, Iaremenko, Oleg, Mikitenko, Ganna, Kavanaugh, Arthur, Luijtens, Kristel, Curtis, Jeffrey, Schiff, Michael, Kvien, Tore, Khanna, Dinesh, Furst, Dan, Behrens, Frank, Koehm, Michaela, Scharbatke, Eva C., Kleinert, Stefan, Weyer, Gerd, Tony, Hans-Peter, Burkhardt, Harald, Blunn, Karina J., Williams, Richard B., Young, Adam, McDowell, Jackie, Weinblatt, Michael, Haraoui, Boulos, Mozaffarian, Neelufar, Khraishi, Majed, Alten, Rieke, Gomez-Reino, Juan, Rizzo, Warren, Schechtman, Joy, Kahan, Andre, Vernon, Emma, Taylor, Monet, Hogan, Vanessa, Holweg, Cecile, Kummerfeld, Sarah, Teng, Onno, Townsend, Michael, van Laar, Jacob M., Gullick, Nicola J., De Silva, Chulanie, Kirkham, Bruce W., Roy, Sanjoy, Emery, P., van der Heijde, D., Keystone, E., Conaghan, P. G., Xu, W., Baratelle, A., Beutler, A., Rahman, M. U., Nikiphorou, Elena, Kiely, Patrick, Walsh, David A., Williams, Richard, Shah, Devron, Knight, Gregory D., Hutchinson, David G., Dass, Shouvik, Atzeni, Fabiola, Vital, Edward M., Bingham, Sarah J., Buch, Maya, Beirne, Paul, Fleischmann, Roy, Dougados, Maxime, Williams, Sarah, Reynard, Mark, Blackler, Laura, Zain, Amir, Oakley, Stephen, Rees, Jonathon, Jones, Tim, Mistlin, Alan, Panayi, Gabriel, Westhovens, Rene, Durez, Patrick, Genant, Harry, Robles, Manuel, Becker, Jean-Claude, Covucci, Allison, Bathon, Joan, Genovese, Mark C., Luggen, Michael, Le Bars, Manuela, Aranda, Richard, Li, Tracy, Elegbe, Ayanbola, Fichtner, Andreas, Strand, Vibeke, Vencovsky, Jiri, Davies, Rebecca, Galloway, James, Hochberg, Marc, Kelly, Sheila, Khan, Nadar, Qi, Keqin, Pappu, Ramesh, Delaet, Ingrid, Luo, Allison, Torbeyns, Anne, Moreland, Larry, Cohen, Roger, Gujrathi, Sheila, Bykerk, Vivian P., Álvaro-Gracia, Jose, Andres Roman Ivorra, Jose, Nurmohamed, Michael T., Bernasconi, Corrado, Stancati, Andrea, Sibilia, Jean, Östör, Andrew, Strangfeld, Anja, Eveslage, Maria, Listing, Joachim, Herzer, Peter, Liebhaber, Anke, Krummel-Lorenz, Brigitte, Zink, Angela, Breedveld, Ferdinand C., Cohen, Stanley B., Matteson, Eric L., Burke, Laura, Chai, Akiko, Reiss, William, Sweetser, Marianne, Shaw, Tim, Ellis, Shawn D., Ehrenstein, Michael R., Notley, Clare A., Yazici, Yusuf, Ince, Akgun, Baraf, Herbert, Malamet, Raymond, Chung, Carol Y., Hughes, Chris, Faurholm, Bjarne, Dell'Accio, Francesco, Manzo, Antonio, Seed, Michael, Eltawil, Noha, Marrelli, Alessandra, Gould, David, Subang, Christina, Al-Kashi, Adam, De Bari, Cosimo, Winyard, Paul, Chernajovsky, Yuti, Nissim, Ahuva, Bingham, Clifton, Fleischmann, Roy M., Furst, Daniel E., Macey, Katherine M., Sweetser, Marianne T., Lehane, Patricia, Farmer, Pamela, Long, Simon G., Kremer, Joel M., Burgos-Vargas, Ruben, Dudler, Jean, Mela, Christopher M., Wegner, Natalia, Lugli, Helena, Quirke, Anne-Marie, Guo, Yonghua, Potempa, Jan, and Venables, Patrick

Abstract

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient die

Published
2017

8. High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci

Author

Kim, Kwangwoo, Bang, So-Young, Lee, Hye-Soon, Cho, Soo-Kyung, Choi, Chan-Bum, Sung, Yoon-Kyoung, Kim, Tae-Hwan, Jun, Jae-Bum, Yoo, Dae Hyun, Kang, Young Mo, Kim, Seong-Kyu, Suh, Chang-Hee, Shim, Seung-Cheol, Lee, Shin-Seok, Lee, Jisoo, Chung, Won Tae, Choe, Jung-Yoon, Shin, Hyoung Doo, Lee, Jong-Young, Han, Bok-Ghee, Nath, Swapan K., Eyre, Steve, Bowes, John, Pappas, Dimitrios A., Kremer, Joel M., Gonzalez-Gay, Miguel A., Rodriguez-Rodriguez, Luis, Ärlestig, Lisbeth, Okada, Yukinori, Diogo, Dorothee, Liao, Katherine P., Karlson, Elizabeth W., Raychaudhuri, Soumya, Rantapää-Dahlqvist, Solbritt, Martin, Javier, Klareskog, Lars, Padyukov, Leonid, Gregersen, Peter K., Worthington, Jane, Greenberg, Jeffrey D., Plenge, Robert M., Bae, Sang-Cheol, Kim, Kwangwoo, Bang, So-Young, Lee, Hye-Soon, Cho, Soo-Kyung, Choi, Chan-Bum, Sung, Yoon-Kyoung, Kim, Tae-Hwan, Jun, Jae-Bum, Yoo, Dae Hyun, Kang, Young Mo, Kim, Seong-Kyu, Suh, Chang-Hee, Shim, Seung-Cheol, Lee, Shin-Seok, Lee, Jisoo, Chung, Won Tae, Choe, Jung-Yoon, Shin, Hyoung Doo, Lee, Jong-Young, Han, Bok-Ghee, Nath, Swapan K., Eyre, Steve, Bowes, John, Pappas, Dimitrios A., Kremer, Joel M., Gonzalez-Gay, Miguel A., Rodriguez-Rodriguez, Luis, Ärlestig, Lisbeth, Okada, Yukinori, Diogo, Dorothee, Liao, Katherine P., Karlson, Elizabeth W., Raychaudhuri, Soumya, Rantapää-Dahlqvist, Solbritt, Martin, Javier, Klareskog, Lars, Padyukov, Leonid, Gregersen, Peter K., Worthington, Jane, Greenberg, Jeffrey D., Plenge, Robert M., and Bae, Sang-Cheol

Abstract

Objective A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45 790 European case-control samples. Results We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5x10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusions This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.

Published
2015
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9. TYK2 Protein-Coding Variants Protect against Rheumatoid Arthritis and Autoimmunity, with No Evidence of Major Pleiotropic Effects on Non-Autoimmune Complex Traits

Author

Diogo, Dorothée, Bastarache, Lisa, Liao, Katherine P., Graham, Robert R., Fulton, Robert S., Greenberg, Jeffrey D., Eyre, Steve, Bowes, John, Cui, Jing, Lee, Annette T., Pappas, Dimitrios A., Kremer, Joel M., Barton, Anne, Coenen, Marieke J. H., Franke, Barbara, Kiemeney, Lambertus A., Mariette, Xavier, Richard-Miceli, Corrine, Canhão, Helena, Fonseca, João E., Vries, Niek de, Tak, Paul P., Crusius, J. Bart A., Nurmohamed, Michael T., Kurreeman, Fina, Mikuls, Ted R., Okada, Yukinori, Stahl, Eli A., Larson, David E., Deluca, Tracie L., O'Laughlin, Michelle, Fronick, Catrina C., Fulton, Lucinda L., Kosoy, Roman, Ransom, Michael, Bhangale, Tushar, Ortmann, Ward, Cagan, Andrew, Gainer, Vivian, Karlson, Elizabeth W., Kohane, Isaac, Murphy, Shawn N., Martín, J., Zhernakova, Alexandra, Klareskog, Lars, Padyukov, Leonid, Worthington, J., Mardis, Elaine R., Seldin, Michael F., Gregersen, Peter K., Behrens, Timothy W., Raychaudhuri, Soumya, Denny, Joshua C., Plenge, Robert M., Diogo, Dorothée, Bastarache, Lisa, Liao, Katherine P., Graham, Robert R., Fulton, Robert S., Greenberg, Jeffrey D., Eyre, Steve, Bowes, John, Cui, Jing, Lee, Annette T., Pappas, Dimitrios A., Kremer, Joel M., Barton, Anne, Coenen, Marieke J. H., Franke, Barbara, Kiemeney, Lambertus A., Mariette, Xavier, Richard-Miceli, Corrine, Canhão, Helena, Fonseca, João E., Vries, Niek de, Tak, Paul P., Crusius, J. Bart A., Nurmohamed, Michael T., Kurreeman, Fina, Mikuls, Ted R., Okada, Yukinori, Stahl, Eli A., Larson, David E., Deluca, Tracie L., O'Laughlin, Michelle, Fronick, Catrina C., Fulton, Lucinda L., Kosoy, Roman, Ransom, Michael, Bhangale, Tushar, Ortmann, Ward, Cagan, Andrew, Gainer, Vivian, Karlson, Elizabeth W., Kohane, Isaac, Murphy, Shawn N., Martín, J., Zhernakova, Alexandra, Klareskog, Lars, Padyukov, Leonid, Worthington, J., Mardis, Elaine R., Seldin, Michael F., Gregersen, Peter K., Behrens, Timothy W., Raychaudhuri, Soumya, Denny, Joshua C., and Plenge, Robert M.

Abstract

Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3x10-21), A928V (rs35018800, OR = 0.53, P = 1.2x10-9), and I684S (rs12720356, OR = 0.86, P = 4.6x10-7). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6x10-18), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; Pomnibus = 0.005). Finally, in a phenome-wide association study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR) in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases.

Published
2015

10. Genetics of rheumatoid arthritis contributes to biology and drug discovery

Author

Okada, Yukinori, Wu, Di, Trynka, Gosia, Raj, Towfique, Terao, Chikashi, Ikari, Katsunori, Kochi, Yuta, Ohmura, Koichiro, Suzuki, Akari, Yoshida, Shinji, Graham, Robert R, Manoharan, Arun, Ortmann, Ward, Bhangale, Tushar, Denny, Joshua C, Carroll, Robert J, Eyler, Anne E, Greenberg, Jeffrey D, Kremer, Joel M, Pappas, Dimitrios A, Jiang, Lei, Yin, Jian, Ye, Lingying, Su, Ding-Feng, Yang, Jian, Xie, Gang, Keystone, Ed, Westra, Harm-Jan, Esko, Tonu, Metspalu, Andres, Zhou, Xuezhong, Gupta, Namrata, Mirel, Daniel, Stahl, Eli A, Diogo, Dorothee, Cui, Jing, Liao, Katherine, Guo, Michael H, Myouzen, Keiko, Kawaguchi, Takahisa, Coenen, Marieke JH, van Riel, Piet LCM, van de laar, Mart AFJ, Guchelaar, Henk-Jan, Huizinga, Tom WJ, Dieude, Philippe, Mariette, Xavier, Bridges, S Louis, Jr., Zhernakova, Alexandra, Toes, Rene EM, Tak, Paul P, Miceli-Richard, Corinne, Bang, So-Young, Lee, Hye-Soon, Martin, Javier, Gonzalez-Gay, Miguel A, Rodriguez-Rodriguez, Luis, Rantapää-Dahlqvist, Solbritt, Ärlestig, Lisbeth, Choi, Hyon K, Kamatani, Yoichiro, Galan, Pilar, Lathrop, Mark, Eyre, Steve, Bowes, John, Barton, Anne, de Vries, Niek, Moreland, Larry W, Criswell, Lindsey A, Karlson, Elizabeth W, Taniguchi, Atsuo, Yamada, Ryo, Kubo, Michiaki, Liu, Jun S, Bae, Sang-Cheol, Worthington, Jane, Padyukov, Leonid, Klareskog, Lars, Gregersen, Peter K, Raychaudhuri, Soumya, Stranger, Barbara E, De Jager, Philip L, Franke, Lude, Visscher, Peter M, Brown, Matthew A, Yamanaka, Hisashi, Mimori, Tsuneyo, Takahashi, Atsushi, Xu, Huji, Behrens, Timothy W, Siminovitch, Katherine A, Momohara, Shigeki, Matsuda, Fumihiko, Yamamoto, Kazuhiko, Plenge, Robert M, Okada, Yukinori, Wu, Di, Trynka, Gosia, Raj, Towfique, Terao, Chikashi, Ikari, Katsunori, Kochi, Yuta, Ohmura, Koichiro, Suzuki, Akari, Yoshida, Shinji, Graham, Robert R, Manoharan, Arun, Ortmann, Ward, Bhangale, Tushar, Denny, Joshua C, Carroll, Robert J, Eyler, Anne E, Greenberg, Jeffrey D, Kremer, Joel M, Pappas, Dimitrios A, Jiang, Lei, Yin, Jian, Ye, Lingying, Su, Ding-Feng, Yang, Jian, Xie, Gang, Keystone, Ed, Westra, Harm-Jan, Esko, Tonu, Metspalu, Andres, Zhou, Xuezhong, Gupta, Namrata, Mirel, Daniel, Stahl, Eli A, Diogo, Dorothee, Cui, Jing, Liao, Katherine, Guo, Michael H, Myouzen, Keiko, Kawaguchi, Takahisa, Coenen, Marieke JH, van Riel, Piet LCM, van de laar, Mart AFJ, Guchelaar, Henk-Jan, Huizinga, Tom WJ, Dieude, Philippe, Mariette, Xavier, Bridges, S Louis, Jr., Zhernakova, Alexandra, Toes, Rene EM, Tak, Paul P, Miceli-Richard, Corinne, Bang, So-Young, Lee, Hye-Soon, Martin, Javier, Gonzalez-Gay, Miguel A, Rodriguez-Rodriguez, Luis, Rantapää-Dahlqvist, Solbritt, Ärlestig, Lisbeth, Choi, Hyon K, Kamatani, Yoichiro, Galan, Pilar, Lathrop, Mark, Eyre, Steve, Bowes, John, Barton, Anne, de Vries, Niek, Moreland, Larry W, Criswell, Lindsey A, Karlson, Elizabeth W, Taniguchi, Atsuo, Yamada, Ryo, Kubo, Michiaki, Liu, Jun S, Bae, Sang-Cheol, Worthington, Jane, Padyukov, Leonid, Klareskog, Lars, Gregersen, Peter K, Raychaudhuri, Soumya, Stranger, Barbara E, De Jager, Philip L, Franke, Lude, Visscher, Peter M, Brown, Matthew A, Yamanaka, Hisashi, Mimori, Tsuneyo, Takahashi, Atsushi, Xu, Huji, Behrens, Timothy W, Siminovitch, Katherine A, Momohara, Shigeki, Matsuda, Fumihiko, Yamamoto, Kazuhiko, and Plenge, Robert M

Abstract

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

Published
2014
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11. Rapid Onset of Clinical Benefit Is Associated with a Reduction in Validated Biomarkers of Disease in Patients with Rheumatoid Arthritis Treated with Mavrilimumab, a Human Monoclonal Antibody Targeting GM-CSFRa

Author

McInnes, Iain B., Burmester, Gerd, Kremer, Joel M., Miranda, Pedro, Korkosz, Mariusz, Vencovsky, Jiri, Rubbert-Roth, Andrea, Mysler, Eduardo, Close, David, Sleeman, Matthew A., Godwood, Alex, Sandbach, Sara, Ryan, Patricia C., Sinibaldi, Dominic, White, Wendy, Defranoux, Nadine A., Weinblatt, Michael, McInnes, Iain B., Burmester, Gerd, Kremer, Joel M., Miranda, Pedro, Korkosz, Mariusz, Vencovsky, Jiri, Rubbert-Roth, Andrea, Mysler, Eduardo, Close, David, Sleeman, Matthew A., Godwood, Alex, Sandbach, Sara, Ryan, Patricia C., Sinibaldi, Dominic, White, Wendy, Defranoux, Nadine A., and Weinblatt, Michael

Published
2014

12. Efficacy and Safety/Tolerability of Mavrilimumab, a Human GM-CSFRa Monoclonal Antibody in Patients with Rheumatoid Arthritis.

Author

Burmester, Gerd, McInnes, Iain B., Kremer, Joel M., Miranda, Pedro, Korkosz, Mariusz, Vencovsky, Jiri, Rubbert-Roth, Andrea, Mysler, Eduardo, Sandbach, Sara, Sleeman, Matthew A., Godwood, Alex, Close, David, Weinblatt, Michael, Burmester, Gerd, McInnes, Iain B., Kremer, Joel M., Miranda, Pedro, Korkosz, Mariusz, Vencovsky, Jiri, Rubbert-Roth, Andrea, Mysler, Eduardo, Sandbach, Sara, Sleeman, Matthew A., Godwood, Alex, Close, David, and Weinblatt, Michael

Published
2014

13. Rapid Onset of Clinical Benefit Is Associated with a Reduction in Validated Biomarkers of Disease in Patients with Rheumatoid Arthritis Treated with Mavrilimumab, a Human Monoclonal Antibody Targeting GM-CSFRa

Author

McInnes, Iain B., Burmester, Gerd, Kremer, Joel M., Miranda, Pedro, Korkosz, Mariusz, Vencovsky, Jiri, Rubbert-Roth, Andrea, Mysler, Eduardo, Close, David, Sleeman, Matthew A., Godwood, Alex, Sandbach, Sara, Ryan, Patricia C., Sinibaldi, Dominic, White, Wendy, Defranoux, Nadine A., Weinblatt, Michael, McInnes, Iain B., Burmester, Gerd, Kremer, Joel M., Miranda, Pedro, Korkosz, Mariusz, Vencovsky, Jiri, Rubbert-Roth, Andrea, Mysler, Eduardo, Close, David, Sleeman, Matthew A., Godwood, Alex, Sandbach, Sara, Ryan, Patricia C., Sinibaldi, Dominic, White, Wendy, Defranoux, Nadine A., and Weinblatt, Michael

Published
2014

14. Efficacy and Safety/Tolerability of Mavrilimumab, a Human GM-CSFRa Monoclonal Antibody in Patients with Rheumatoid Arthritis.

Author

Burmester, Gerd, McInnes, Iain B., Kremer, Joel M., Miranda, Pedro, Korkosz, Mariusz, Vencovsky, Jiri, Rubbert-Roth, Andrea, Mysler, Eduardo, Sandbach, Sara, Sleeman, Matthew A., Godwood, Alex, Close, David, Weinblatt, Michael, Burmester, Gerd, McInnes, Iain B., Kremer, Joel M., Miranda, Pedro, Korkosz, Mariusz, Vencovsky, Jiri, Rubbert-Roth, Andrea, Mysler, Eduardo, Sandbach, Sara, Sleeman, Matthew A., Godwood, Alex, Close, David, and Weinblatt, Michael

Published
2014

15. This title is unavailable for guests, please login to see more information.

Author

Mehta, Puja, Holder, Susan, Fisher, Benjamin, Vincent, Tonia, Nadesalingam, Kavitha, Maciver, Helen, Shingler, Wendy, Bakshi, Jyoti, Hassan, Sadon, D'Cruz, David, Chan, Antoni, Litwic, Anna E., McCrae, Fiona, Seth, Rakhi, Nandagudi, Anupama, Jury, Elizabeth, Isenberg, David, Karjigi, Uma, Paul, Anupam, Rees, Frances, O'Dowd, Emma, Kinnear, William, Johnson, Simon, Lanyon, Peter, Stevens, Richard, Narayan, Nehal, Marguerie, Christopher, Robinson, Helena, Ffolkes, Lorrette, Worsnop, Fiona, Ostlere, Lucy, Kiely, Patrick, Dharmapalaiah, Chethana, Hassan, Nada, Bharadwaj, Anurag, Skibinska, Malgorzata, Gendi, Nagui, Davies, Emma J., Akil, Mohammed, Kilding, Rachael, Ramachandran Nair, Jagdish, Walsh, Maeve, Farrar, Wendy, Thompson, Robert N., Borukhson, Liubov, McFadyen, Charles, Singh, Deepwant, Rajagopal, Vivek, Chan, Angela Marie L., Wearn Koh, Li, Christie, Jennifer D., Croot, Lorraine, Gayed, Mary, Disney, Benjamin, Singhal, Saket, Grindulis, Karl, Reynolds, Timothy D., Conway, Katie, Williams, Debbie, Quin, John, Dean, Gillian, Churchill, Duncan, Walker-Bone, Karen E., Goff, Iain, Reynolds, Gary, Grove, Matthew, Patel, Priya, Lazarus, Mark N., Roncaroli, Frederico, Gabriel, Carolyn, Kinderlerer, Anne R., Nikiphorou, Elena, Hall, Frances C., Bruce, Ellen, Gray, Leanne, Krutikov, Maria, Wig, Surabhi, Bruce, Ian, D'Agostino, Maria A., Wakefield, Richard, Berner Hammer, Hilde, Vittecoq, Olivier, Galeazzi, Mauro, Balint, Peter, Filippucci, Emilio, Moller, Ingrid, Iagnocco, Annamaria, Naredo, Esperanza, Ostergaard, Mikkel, Gaillez, Corine, Kerselaers, Wendy, Van Holder, Karina, Le Bars, Manuela, Stone, Millicent A., Williams, Francis, Wolber, Lisa, Karppinen, Jaro, Maatta, Juhani, Thompson, Ben, Atchia, Ismael, Lorenzi, Alice, Raftery, Graham, Platt, Phil, Platt, Philip N., Pratt, Arthur, Turmezei, Thomas D., Treece, Graham M., Gee, Andrew H., Poole, Kenneth E., Chandratre, Priyanka N., Roddy, Edward, Clarson, Lorna, Richardson, Jane, Hider, Samantha, Mallen, Christian, Lieberman, Abigail, Prouse, Peter J., Mahendran, Prini, Samarawickrama, Amanda, Ottery, Faith D., Yood, Robert, Wolfson, Marsha, Ang, Andrea, Riches, Philip, Thomson, Janet, Nuki, George, Humphreys, Jennifer, Verstappen, Suzanne M., Chipping, Jacqueline, Hyrich, Kimme, Marshall, Tarnya, Symmons, Deborah P., Roy, Matthew, Kirwan, John R., Marshall, Robert W., Matcham, Faith, Scott, Ian C., Rayner, Lauren, Hotopf, Matthew, Kingsley, Gabrielle H., Scott, David L., Steer, Sophia, Ma, Margaret H., Dahanayake, Chanaka, Kingsley, Gabrielle, Cope, Andrew, Wernham, Aaron, Ward, Lorna, Carruthers, David, Deeming, Alison, Buckley, Christopher, Raza, Karim, De Pablo, Paola, Carpenter, Lewis, Jayakumar, Keeranur, Solymossy, Csilla, Dixey, Josh, Young, Adam, Singh, Animesh, Penn, Henry, Ellerby, Nicholas, Mattey, Derek L., Packham, Jonathan, Dawes, Peter, Hider, Samantha L., Ng, Nora, Humby, Frances, Bombardieri, Michele, Kelly, Stephen, Di Cicco, Maria, Dadoun, Sabrina, Hands, Rebecca, Rocher, Vidalba, Kidd, Bruce, Pyne, Dev, Pitzalis, Costantino, Poore, Sophie, Hutchinson, David, Low, Audrey, Lunt, Mark, Mercer, Louise, Galloway, James, Davies, Rebecca, Watson, Kath, Dixon, Will, Symmons, Deborah, Watson, Kath D., Dixon, William G., Hyrich, Kimme L., Malik, Saadia P., Kelly, Clive, Hamilton, Jennifer, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Harris, Helen E., Tweedie, Fiona, Skaparis, Yiannis, White, Marie, Scott, Nicola, Samson, Kay, Mercieca, Cecilia, Clarke, Shane, Warner, Alexander J., Verstappen, Suzanne, Chan, Esther, Woodhead, Felix A., Nisar, Mohamed, Arthanari, S., Dawson, Julie, Sathi, Nav, Ahmad, Yasmeen, Koduri, Gouri, Cumming, Jo, Stannett, Peter, Hull, Richard, Metsios, George, Stavropoulos Kalinoglou, Antonios, Veldhuijzen van Zanten, Jet J., Nightingale, Peter, Koutedakis, Yiannis, Kitas, George D., Williams, Peter, Walsh, David, Perry, Elizabeth, de-Soyza, Anthony, Moullaali, Thomas, Eggleton, Paul, Stavropoulos-Kalinoglou, Antonios, Sandoo, Aamer, de Pablo, Paola, Maggs, Fiona, Faizal, Abdul, Pugh, Mark, Jobanputra, Paresh, Kehoe, Oksana, Cartwright, Alison, Askari, Ayman, El Haj, Alicia, Middleton, Jim, Aynsley, Sarah, Hardy, Jacob, Veale, Douglas, Fearon, Ursula, Wilson, Gerry, Muthana, Munitta, Fossati, G., Healy, L., Nesbitt, A., Becerra, Elena, Leandro, Maria J., De La Torre, Inmaculada, Cambridge, Geraldine, Nelson, P. N., Roden, D., Shaw, M., Davari Ejtehadi, Hora, Nevill, A., Freimanis, G., Hooley, P., Bowman, S., Alavi, A., Axford, J., Veitch, A. M., Tugnet, N., Rylance, P. B., Hawtree, Sarah, Mark Wilkinson, J., Wilson, Anthony G., Woon Kam, Ngar, Filter, Andrew, Croft, Adam P., Naylor, Amy, Zimmermann, Birgit, Hardie, Debbie, Desanti, Guillaume, Jaurez, Maria, Muller-Ladner, Ulf, Filer, Andrew, Neumann, Elena, Movahedi, Mohammad, Ray, David W., Burmester, Gerd R., Matucci-Cerinic, Marco, Navarro-Blasco, Francisco, Kary, Sonja, Unnebrink, Kristina, Kupper, Hartmut, Mukherjee, Sandeep, Cornell, Patricia, Richards, Selwyn, Rahmeh, Fouz, Thompson, Paul W., Westlake, Sarah L., Javaid, Muhammad K., Batra, Rajbir, Chana, Jasroop, Round, Gemma, Judge, Andrew, Taylor, Peter, Patel, Sanjeev, Cooper, Cyrus, Ravindran, Vinod, Bingham, Clifton O., Weinblatt, Michael E., Mendelsohn, Alan, Kim, Lilianne, Mack, Michael, Lu, Jiandong, Baker, Daniel, Westhovens, Rene, Hewitt, Jamie, Han, Chenglong, Keystone, Edward C., Fleischmann, Roy, Smolen, Josef, Emery, Paul, Genovese, Mark, Doyle, Mittie, Hsia, Elizabeth C., Hart, Jennifer C., Harland, Dave, Gibbons, Carl, Pang, Hok, Huertas, Catherine, Diamantopoulos, Alex, Dejonckheere, Fred, Clowse, M., Wolf, D., Stach, C., Kosutic, G., Williams, S., Terpstra, I., Mahadevan, U., Ferraccioli, G., Samborski, W., Berenbaum, F., Davies, O., Koetse, W., Bennett, B., Burkhardt, H., Luijtens, K., van der Heijde, Desiree, Mariette, X., van Vollenhoven, Ronald F., Bykerk, V., de Longueville, M., Arendt, C., Cush, J., Khan, Afsha, Maclaren, Zoe, Dubash, Sayam, Chalam, Venkat C., Sheeran, Tom, Price, Tom, Baskar, Sangeetha, Mulherin, Diarmuid, Molloy, Cauline, Keay, Fiona, Heritage, Caroline, Douglas, Barbara, Schiff, Michael H., Khanna, Dinesh, Furst, Daniel E., Maldonado, Michael A., Li, Wanying, Sasso, Eric H., Emerling, Daniel, Cavet, Guy, Ford, Kerri, Mackenzie-Green, Bronwen, Collins, David, Price, Elizabeth, Williamson, Lyn, Golla, Janardhana, Vagadia, Vipul, Morrison, Elaine, Tierney, Ann, Wilson, Hilary, Hunter, John, Reddy, Venkat, Moore, Samantha, Ehrenstein, Michael, Benson, Claire, Wray, Maria, Cairns, Andrew, Wright, Gary, Pendleton, Adrian, McHenry, Michelle, Taggart, Allister, Bell, Aubrey, Bosworth, Ailsa, Cox, Maureen, Johnston, Graeme, Shah, Preeti, O'Brien, Anne, Jones, Peter, Sargeant, Ify, Bukhari, Marwan, Nusslein, Hubert, Alten, Rieke, Lorenz, Hannes M., Boumpas, Dimitrios, Nurmohamed, Michael T., Bensen, William, Peter, Hans-Hartmut, Rainer, Franz, Pavelka, Karel, Chartier, Melanie, Poncet, Coralie, Rauch, Christiane, Lempp, Heidi, Hofmann, Darija, Adu, Aderonke, Congreve, Carron, Dobson, Joanne, Rose, Diana, Simpson, Carol, Wykes, Til, Ibrahim, Fowzia, Schiff, Michael, Nash, Peter, Durez, Patrick, Kaine, Jeffrey, Delaet, Ingrid, Kelly, Sheila, Maldonado, Michael, Patel, Salil, Jones, Graeme, Sebba, Anthony, Lepley, Denise, Devenport, Jenny, Bernasconi, Corrado, Smart, Devi, Mpofu, Chiedzo, Gomez-Reino, Juan J., Verma, Inderjeet, Kaur, Jaspreet, Syngle, Ashit, Krishan, Pawan, Vohra, Kanchan, Kaur, Ladbans, Garg, Nidhi, Chhabara, Monica, Gibson, Kellie, Woodburn, James, Telfer, Scott, Buckley, Felicity, Finckh, Axel, Huizinga, Tom W., Jansen, Jeroen P., Rubbert-Roth, Andrea, Scali, Juan J., Kremer, Joel M., Pitts, Laura, Vernon, Emma, Sharif, Mohammed I., Das, Sudipto, Helliwell, Philip, Sokoll, Katharina, Vital, Edward M., Mehta, Puja, Holder, Susan, Fisher, Benjamin, Vincent, Tonia, Nadesalingam, Kavitha, Maciver, Helen, Shingler, Wendy, Bakshi, Jyoti, Hassan, Sadon, D'Cruz, David, Chan, Antoni, Litwic, Anna E., McCrae, Fiona, Seth, Rakhi, Nandagudi, Anupama, Jury, Elizabeth, Isenberg, David, Karjigi, Uma, Paul, Anupam, Rees, Frances, O'Dowd, Emma, Kinnear, William, Johnson, Simon, Lanyon, Peter, Stevens, Richard, Narayan, Nehal, Marguerie, Christopher, Robinson, Helena, Ffolkes, Lorrette, Worsnop, Fiona, Ostlere, Lucy, Kiely, Patrick, Dharmapalaiah, Chethana, Hassan, Nada, Bharadwaj, Anurag, Skibinska, Malgorzata, Gendi, Nagui, Davies, Emma J., Akil, Mohammed, Kilding, Rachael, Ramachandran Nair, Jagdish, Walsh, Maeve, Farrar, Wendy, Thompson, Robert N., Borukhson, Liubov, McFadyen, Charles, Singh, Deepwant, Rajagopal, Vivek, Chan, Angela Marie L., Wearn Koh, Li, Christie, Jennifer D., Croot, Lorraine, Gayed, Mary, Disney, Benjamin, Singhal, Saket, Grindulis, Karl, Reynolds, Timothy D., Conway, Katie, Williams, Debbie, Quin, John, Dean, Gillian, Churchill, Duncan, Walker-Bone, Karen E., Goff, Iain, Reynolds, Gary, Grove, Matthew, Patel, Priya, Lazarus, Mark N., Roncaroli, Frederico, Gabriel, Carolyn, Kinderlerer, Anne R., Nikiphorou, Elena, Hall, Frances C., Bruce, Ellen, Gray, Leanne, Krutikov, Maria, Wig, Surabhi, Bruce, Ian, D'Agostino, Maria A., Wakefield, Richard, Berner Hammer, Hilde, Vittecoq, Olivier, Galeazzi, Mauro, Balint, Peter, Filippucci, Emilio, Moller, Ingrid, Iagnocco, Annamaria, Naredo, Esperanza, Ostergaard, Mikkel, Gaillez, Corine, Kerselaers, Wendy, Van Holder, Karina, Le Bars, Manuela, Stone, Millicent A., Williams, Francis, Wolber, Lisa, Karppinen, Jaro, Maatta, Juhani, Thompson, Ben, Atchia, Ismael, Lorenzi, Alice, Raftery, Graham, Platt, Phil, Platt, Philip N., Pratt, Arthur, Turmezei, Thomas D., Treece, Graham M., Gee, Andrew H., Poole, Kenneth E., Chandratre, Priyanka N., Roddy, Edward, Clarson, Lorna, Richardson, Jane, Hider, Samantha, Mallen, Christian, Lieberman, Abigail, Prouse, Peter J., Mahendran, Prini, Samarawickrama, Amanda, Ottery, Faith D., Yood, Robert, Wolfson, Marsha, Ang, Andrea, Riches, Philip, Thomson, Janet, Nuki, George, Humphreys, Jennifer, Verstappen, Suzanne M., Chipping, Jacqueline, Hyrich, Kimme, Marshall, Tarnya, Symmons, Deborah P., Roy, Matthew, Kirwan, John R., Marshall, Robert W., Matcham, Faith, Scott, Ian C., Rayner, Lauren, Hotopf, Matthew, Kingsley, Gabrielle H., Scott, David L., Steer, Sophia, Ma, Margaret H., Dahanayake, Chanaka, Kingsley, Gabrielle, Cope, Andrew, Wernham, Aaron, Ward, Lorna, Carruthers, David, Deeming, Alison, Buckley, Christopher, Raza, Karim, De Pablo, Paola, Carpenter, Lewis, Jayakumar, Keeranur, Solymossy, Csilla, Dixey, Josh, Young, Adam, Singh, Animesh, Penn, Henry, Ellerby, Nicholas, Mattey, Derek L., Packham, Jonathan, Dawes, Peter, Hider, Samantha L., Ng, Nora, Humby, Frances, Bombardieri, Michele, Kelly, Stephen, Di Cicco, Maria, Dadoun, Sabrina, Hands, Rebecca, Rocher, Vidalba, Kidd, Bruce, Pyne, Dev, Pitzalis, Costantino, Poore, Sophie, Hutchinson, David, Low, Audrey, Lunt, Mark, Mercer, Louise, Galloway, James, Davies, Rebecca, Watson, Kath, Dixon, Will, Symmons, Deborah, Watson, Kath D., Dixon, William G., Hyrich, Kimme L., Malik, Saadia P., Kelly, Clive, Hamilton, Jennifer, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Harris, Helen E., Tweedie, Fiona, Skaparis, Yiannis, White, Marie, Scott, Nicola, Samson, Kay, Mercieca, Cecilia, Clarke, Shane, Warner, Alexander J., Verstappen, Suzanne, Chan, Esther, Woodhead, Felix A., Nisar, Mohamed, Arthanari, S., Dawson, Julie, Sathi, Nav, Ahmad, Yasmeen, Koduri, Gouri, Cumming, Jo, Stannett, Peter, Hull, Richard, Metsios, George, Stavropoulos Kalinoglou, Antonios, Veldhuijzen van Zanten, Jet J., Nightingale, Peter, Koutedakis, Yiannis, Kitas, George D., Williams, Peter, Walsh, David, Perry, Elizabeth, de-Soyza, Anthony, Moullaali, Thomas, Eggleton, Paul, Stavropoulos-Kalinoglou, Antonios, Sandoo, Aamer, de Pablo, Paola, Maggs, Fiona, Faizal, Abdul, Pugh, Mark, Jobanputra, Paresh, Kehoe, Oksana, Cartwright, Alison, Askari, Ayman, El Haj, Alicia, Middleton, Jim, Aynsley, Sarah, Hardy, Jacob, Veale, Douglas, Fearon, Ursula, Wilson, Gerry, Muthana, Munitta, Fossati, G., Healy, L., Nesbitt, A., Becerra, Elena, Leandro, Maria J., De La Torre, Inmaculada, Cambridge, Geraldine, Nelson, P. N., Roden, D., Shaw, M., Davari Ejtehadi, Hora, Nevill, A., Freimanis, G., Hooley, P., Bowman, S., Alavi, A., Axford, J., Veitch, A. M., Tugnet, N., Rylance, P. B., Hawtree, Sarah, Mark Wilkinson, J., Wilson, Anthony G., Woon Kam, Ngar, Filter, Andrew, Croft, Adam P., Naylor, Amy, Zimmermann, Birgit, Hardie, Debbie, Desanti, Guillaume, Jaurez, Maria, Muller-Ladner, Ulf, Filer, Andrew, Neumann, Elena, Movahedi, Mohammad, Ray, David W., Burmester, Gerd R., Matucci-Cerinic, Marco, Navarro-Blasco, Francisco, Kary, Sonja, Unnebrink, Kristina, Kupper, Hartmut, Mukherjee, Sandeep, Cornell, Patricia, Richards, Selwyn, Rahmeh, Fouz, Thompson, Paul W., Westlake, Sarah L., Javaid, Muhammad K., Batra, Rajbir, Chana, Jasroop, Round, Gemma, Judge, Andrew, Taylor, Peter, Patel, Sanjeev, Cooper, Cyrus, Ravindran, Vinod, Bingham, Clifton O., Weinblatt, Michael E., Mendelsohn, Alan, Kim, Lilianne, Mack, Michael, Lu, Jiandong, Baker, Daniel, Westhovens, Rene, Hewitt, Jamie, Han, Chenglong, Keystone, Edward C., Fleischmann, Roy, Smolen, Josef, Emery, Paul, Genovese, Mark, Doyle, Mittie, Hsia, Elizabeth C., Hart, Jennifer C., Harland, Dave, Gibbons, Carl, Pang, Hok, Huertas, Catherine, Diamantopoulos, Alex, Dejonckheere, Fred, Clowse, M., Wolf, D., Stach, C., Kosutic, G., Williams, S., Terpstra, I., Mahadevan, U., Ferraccioli, G., Samborski, W., Berenbaum, F., Davies, O., Koetse, W., Bennett, B., Burkhardt, H., Luijtens, K., van der Heijde, Desiree, Mariette, X., van Vollenhoven, Ronald F., Bykerk, V., de Longueville, M., Arendt, C., Cush, J., Khan, Afsha, Maclaren, Zoe, Dubash, Sayam, Chalam, Venkat C., Sheeran, Tom, Price, Tom, Baskar, Sangeetha, Mulherin, Diarmuid, Molloy, Cauline, Keay, Fiona, Heritage, Caroline, Douglas, Barbara, Schiff, Michael H., Khanna, Dinesh, Furst, Daniel E., Maldonado, Michael A., Li, Wanying, Sasso, Eric H., Emerling, Daniel, Cavet, Guy, Ford, Kerri, Mackenzie-Green, Bronwen, Collins, David, Price, Elizabeth, Williamson, Lyn, Golla, Janardhana, Vagadia, Vipul, Morrison, Elaine, Tierney, Ann, Wilson, Hilary, Hunter, John, Reddy, Venkat, Moore, Samantha, Ehrenstein, Michael, Benson, Claire, Wray, Maria, Cairns, Andrew, Wright, Gary, Pendleton, Adrian, McHenry, Michelle, Taggart, Allister, Bell, Aubrey, Bosworth, Ailsa, Cox, Maureen, Johnston, Graeme, Shah, Preeti, O'Brien, Anne, Jones, Peter, Sargeant, Ify, Bukhari, Marwan, Nusslein, Hubert, Alten, Rieke, Lorenz, Hannes M., Boumpas, Dimitrios, Nurmohamed, Michael T., Bensen, William, Peter, Hans-Hartmut, Rainer, Franz, Pavelka, Karel, Chartier, Melanie, Poncet, Coralie, Rauch, Christiane, Lempp, Heidi, Hofmann, Darija, Adu, Aderonke, Congreve, Carron, Dobson, Joanne, Rose, Diana, Simpson, Carol, Wykes, Til, Ibrahim, Fowzia, Schiff, Michael, Nash, Peter, Durez, Patrick, Kaine, Jeffrey, Delaet, Ingrid, Kelly, Sheila, Maldonado, Michael, Patel, Salil, Jones, Graeme, Sebba, Anthony, Lepley, Denise, Devenport, Jenny, Bernasconi, Corrado, Smart, Devi, Mpofu, Chiedzo, Gomez-Reino, Juan J., Verma, Inderjeet, Kaur, Jaspreet, Syngle, Ashit, Krishan, Pawan, Vohra, Kanchan, Kaur, Ladbans, Garg, Nidhi, Chhabara, Monica, Gibson, Kellie, Woodburn, James, Telfer, Scott, Buckley, Felicity, Finckh, Axel, Huizinga, Tom W., Jansen, Jeroen P., Rubbert-Roth, Andrea, Scali, Juan J., Kremer, Joel M., Pitts, Laura, Vernon, Emma, Sharif, Mohammed I., Das, Sudipto, Helliwell, Philip, Sokoll, Katharina, and Vital, Edward M.

16. Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Author

Nishikawa, Masataka, Owaki, Hajime, Fuji, Takeshi, Soliman, Moetaza M., Ashcroft, Darren M., Watson, Kath D., Lunt, Mark, Symmons, Deborah, Hyrich, Kimme L., Atkinson, Francesca, Malik, Saadia, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Hamilton, Jennifer, Kelly, Clive, Burmester, Gerd, Kary, Sonja, Unnebrink, Kristina, Guérette, Benoit, Oezer, Uemit, Kupper, Hartmut, Dennison, Elaine, Jameson, Karen, Hyrich, Kimme, Watson, Kath, Landewe, Robert, Keystone, Edward, Smolen, Josef, Goldring, Mary, Patra, Kaushik, Cifaldi, Mary, van der Heijde, Désirée, Lloyd, Lois A., Owen, Catherine, Breslin, Anne, Ahmad, Yasmeen, Emery, Paul, Matteson, E. L., Genovese, M., Sague, S., Hsia, E. C., Doyle, M. K., Fan, H., Elashoff, M., Kirkham, Bruce, Wasco, M. C., Bathon, J., Fleischmann, R., Genovese, M. C., Liu, H., Goldman, J., Leirisalo-Repo, M., Zanetakis, E., El-Kadi, H., Kellner, H., Bolce, R., Wang, J., Dehoratius, R., Decktor, D., Kremer, J., Taylor, Peter, Mendelsohn, A., Baker, D., Kim, L., Ritchlin, C., Mariette, Xavier, Matucci Cerenic, Marco, Pavelka, Karel, van Vollenhoven, Ronald, Heatley, Rebecca, Walsh, Claire, Lawson, Richard, Reynolds, Alan, Iaremenko, Oleg, Mikitenko, Ganna, Kavanaugh, Arthur, Luijtens, Kristel, Curtis, Jeffrey, Schiff, Michael, Kvien, Tore, Khanna, Dinesh, Furst, Dan, Behrens, Frank, Koehm, Michaela, Scharbatke, Eva C., Kleinert, Stefan, Weyer, Gerd, Tony, Hans-Peter, Burkhardt, Harald, Blunn, Karina J., Williams, Richard B., Young, Adam, McDowell, Jackie, Weinblatt, Michael, Haraoui, Boulos, Mozaffarian, Neelufar, Khraishi, Majed, Alten, Rieke, Gomez-Reino, Juan, Rizzo, Warren, Schechtman, Joy, Kahan, Andre, Vernon, Emma, Taylor, Monet, Hogan, Vanessa, Holweg, Cecile, Kummerfeld, Sarah, Teng, Onno, Townsend, Michael, van Laar, Jacob M., Gullick, Nicola J., De Silva, Chulanie, Kirkham, Bruce W., Roy, Sanjoy, Emery, P., van der Heijde, D., Keystone, E., Conaghan, P. G., Xu, W., Baratelle, A., Beutler, A., Rahman, M. U., Nikiphorou, Elena, Kiely, Patrick, Walsh, David A., Williams, Richard, Shah, Devron, Knight, Gregory D., Hutchinson, David G., Dass, Shouvik, Atzeni, Fabiola, Vital, Edward M., Bingham, Sarah J., Buch, Maya, Beirne, Paul, Fleischmann, Roy, Dougados, Maxime, Williams, Sarah, Reynard, Mark, Blackler, Laura, Zain, Amir, Oakley, Stephen, Rees, Jonathon, Jones, Tim, Mistlin, Alan, Panayi, Gabriel, Westhovens, Rene, Durez, Patrick, Genant, Harry, Robles, Manuel, Becker, Jean-Claude, Covucci, Allison, Bathon, Joan, Genovese, Mark C., Luggen, Michael, Le Bars, Manuela, Aranda, Richard, Li, Tracy, Elegbe, Ayanbola, Fichtner, Andreas, Strand, Vibeke, Vencovsky, Jiri, Davies, Rebecca, Galloway, James, Hochberg, Marc, Kelly, Sheila, Khan, Nadar, Qi, Keqin, Pappu, Ramesh, Delaet, Ingrid, Luo, Allison, Torbeyns, Anne, Moreland, Larry, Cohen, Roger, Gujrathi, Sheila, Bykerk, Vivian P., Álvaro-Gracia, Jose, Andres Roman Ivorra, Jose, Nurmohamed, Michael T., Bernasconi, Corrado, Stancati, Andrea, Sibilia, Jean, Östör, Andrew, Strangfeld, Anja, Eveslage, Maria, Listing, Joachim, Herzer, Peter, Liebhaber, Anke, Krummel-Lorenz, Brigitte, Zink, Angela, Breedveld, Ferdinand C., Cohen, Stanley B., Matteson, Eric L., Burke, Laura, Chai, Akiko, Reiss, William, Sweetser, Marianne, Shaw, Tim, Ellis, Shawn D., Ehrenstein, Michael R., Notley, Clare A., Yazici, Yusuf, Ince, Akgun, Baraf, Herbert, Malamet, Raymond, Chung, Carol Y., Hughes, Chris, Faurholm, Bjarne, Dell'Accio, Francesco, Manzo, Antonio, Seed, Michael, Eltawil, Noha, Marrelli, Alessandra, Gould, David, Subang, Christina, Al-Kashi, Adam, De Bari, Cosimo, Winyard, Paul, Chernajovsky, Yuti, Nissim, Ahuva, Bingham, Clifton, Fleischmann, Roy M., Furst, Daniel E., Macey, Katherine M., Sweetser, Marianne T., Lehane, Patricia, Farmer, Pamela, Long, Simon G., Kremer, Joel M., Burgos-Vargas, Ruben, Dudler, Jean, Mela, Christopher M., Wegner, Natalia, Lugli, Helena, Quirke, Anne-Marie, Guo, Yonghua, Potempa, Jan, Venables, Patrick, Nishikawa, Masataka, Owaki, Hajime, Fuji, Takeshi, Soliman, Moetaza M., Ashcroft, Darren M., Watson, Kath D., Lunt, Mark, Symmons, Deborah, Hyrich, Kimme L., Atkinson, Francesca, Malik, Saadia, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Hamilton, Jennifer, Kelly, Clive, Burmester, Gerd, Kary, Sonja, Unnebrink, Kristina, Guérette, Benoit, Oezer, Uemit, Kupper, Hartmut, Dennison, Elaine, Jameson, Karen, Hyrich, Kimme, Watson, Kath, Landewe, Robert, Keystone, Edward, Smolen, Josef, Goldring, Mary, Patra, Kaushik, Cifaldi, Mary, van der Heijde, Désirée, Lloyd, Lois A., Owen, Catherine, Breslin, Anne, Ahmad, Yasmeen, Emery, Paul, Matteson, E. L., Genovese, M., Sague, S., Hsia, E. C., Doyle, M. K., Fan, H., Elashoff, M., Kirkham, Bruce, Wasco, M. C., Bathon, J., Fleischmann, R., Genovese, M. C., Liu, H., Goldman, J., Leirisalo-Repo, M., Zanetakis, E., El-Kadi, H., Kellner, H., Bolce, R., Wang, J., Dehoratius, R., Decktor, D., Kremer, J., Taylor, Peter, Mendelsohn, A., Baker, D., Kim, L., Ritchlin, C., Mariette, Xavier, Matucci Cerenic, Marco, Pavelka, Karel, van Vollenhoven, Ronald, Heatley, Rebecca, Walsh, Claire, Lawson, Richard, Reynolds, Alan, Iaremenko, Oleg, Mikitenko, Ganna, Kavanaugh, Arthur, Luijtens, Kristel, Curtis, Jeffrey, Schiff, Michael, Kvien, Tore, Khanna, Dinesh, Furst, Dan, Behrens, Frank, Koehm, Michaela, Scharbatke, Eva C., Kleinert, Stefan, Weyer, Gerd, Tony, Hans-Peter, Burkhardt, Harald, Blunn, Karina J., Williams, Richard B., Young, Adam, McDowell, Jackie, Weinblatt, Michael, Haraoui, Boulos, Mozaffarian, Neelufar, Khraishi, Majed, Alten, Rieke, Gomez-Reino, Juan, Rizzo, Warren, Schechtman, Joy, Kahan, Andre, Vernon, Emma, Taylor, Monet, Hogan, Vanessa, Holweg, Cecile, Kummerfeld, Sarah, Teng, Onno, Townsend, Michael, van Laar, Jacob M., Gullick, Nicola J., De Silva, Chulanie, Kirkham, Bruce W., Roy, Sanjoy, Emery, P., van der Heijde, D., Keystone, E., Conaghan, P. G., Xu, W., Baratelle, A., Beutler, A., Rahman, M. U., Nikiphorou, Elena, Kiely, Patrick, Walsh, David A., Williams, Richard, Shah, Devron, Knight, Gregory D., Hutchinson, David G., Dass, Shouvik, Atzeni, Fabiola, Vital, Edward M., Bingham, Sarah J., Buch, Maya, Beirne, Paul, Fleischmann, Roy, Dougados, Maxime, Williams, Sarah, Reynard, Mark, Blackler, Laura, Zain, Amir, Oakley, Stephen, Rees, Jonathon, Jones, Tim, Mistlin, Alan, Panayi, Gabriel, Westhovens, Rene, Durez, Patrick, Genant, Harry, Robles, Manuel, Becker, Jean-Claude, Covucci, Allison, Bathon, Joan, Genovese, Mark C., Luggen, Michael, Le Bars, Manuela, Aranda, Richard, Li, Tracy, Elegbe, Ayanbola, Fichtner, Andreas, Strand, Vibeke, Vencovsky, Jiri, Davies, Rebecca, Galloway, James, Hochberg, Marc, Kelly, Sheila, Khan, Nadar, Qi, Keqin, Pappu, Ramesh, Delaet, Ingrid, Luo, Allison, Torbeyns, Anne, Moreland, Larry, Cohen, Roger, Gujrathi, Sheila, Bykerk, Vivian P., Álvaro-Gracia, Jose, Andres Roman Ivorra, Jose, Nurmohamed, Michael T., Bernasconi, Corrado, Stancati, Andrea, Sibilia, Jean, Östör, Andrew, Strangfeld, Anja, Eveslage, Maria, Listing, Joachim, Herzer, Peter, Liebhaber, Anke, Krummel-Lorenz, Brigitte, Zink, Angela, Breedveld, Ferdinand C., Cohen, Stanley B., Matteson, Eric L., Burke, Laura, Chai, Akiko, Reiss, William, Sweetser, Marianne, Shaw, Tim, Ellis, Shawn D., Ehrenstein, Michael R., Notley, Clare A., Yazici, Yusuf, Ince, Akgun, Baraf, Herbert, Malamet, Raymond, Chung, Carol Y., Hughes, Chris, Faurholm, Bjarne, Dell'Accio, Francesco, Manzo, Antonio, Seed, Michael, Eltawil, Noha, Marrelli, Alessandra, Gould, David, Subang, Christina, Al-Kashi, Adam, De Bari, Cosimo, Winyard, Paul, Chernajovsky, Yuti, Nissim, Ahuva, Bingham, Clifton, Fleischmann, Roy M., Furst, Daniel E., Macey, Katherine M., Sweetser, Marianne T., Lehane, Patricia, Farmer, Pamela, Long, Simon G., Kremer, Joel M., Burgos-Vargas, Ruben, Dudler, Jean, Mela, Christopher M., Wegner, Natalia, Lugli, Helena, Quirke, Anne-Marie, Guo, Yonghua, Potempa, Jan, and Venables, Patrick

Abstract

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient die

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