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1. Factors influencing use of biologic therapy and adoption of treat-to-target recommendations in current European rheumatology practice

Author

Taylor,Peter C, Alten,Rieke, Gomez Reino,Juan J, Caporali,Roberto, Bertin,Philippe, Sullivan,Emma, Wood,Robert, Piercy,James, Vasilescu,Radu, Spurden,Dean, Alvir,Jose, Tarallo,Miriam, Taylor,Peter C, Alten,Rieke, Gomez Reino,Juan J, Caporali,Roberto, Bertin,Philippe, Sullivan,Emma, Wood,Robert, Piercy,James, Vasilescu,Radu, Spurden,Dean, Alvir,Jose, and Tarallo,Miriam

Abstract

Peter C Taylor,1 Rieke Alten,2 Juan J Gomez Reino,3 Roberto Caporali,4 Philippe Bertin,5 Emma Sullivan,6 Robert Wood,6 James Piercy,6 Radu Vasilescu,7 Dean Spurden,8 Jose Alvir,9 Miriam Tarallo10 1Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; 2Department of Internal Medicine II, Rheumatology, Clinical Immunology, and Osteology, Schlosspark Klinik, University Medicine Berlin, Berlin, Germany; 3Experimental and Observational Rheumatology and Rheumatology Unit, Fundacion Ramon Dominguez and Rheumatology, Hospital Clinico Universitario, Santiago de Compostela, Spain; 4Division of Rheumatology, IRCCS Foundation Policlinico S. Matteo, University of Pavia, Pavia, Italy; 5Service de Rhumatologie, CHU Dupuytren, Limoges, France; 6Real-World Evidence and Epidemiology, Adelphi Real World, Bollington, UK; 7Medical Affairs, International Developed Markets, Pfizer, Brussels, Belgium; 8Health Economics and Outcomes Research, Pfizer Ltd, Tadworth, UK; 9Statistical Research and Data Science Center, Global Product Development, Pfizer Inc, New York, NY, USA; 10Patient and Health Impact, Pfizer Italia Srl, Rome, Italy Objective: The aim of this study was to identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices.Methods: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) vs non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis <2 or ≥2 years) and compared according to the approach used (no target = no T2T approach; pragmatic = target different from remission; and aspirational = target set as remission).Results: Data from 2,536 patients were analyze

Published
2018

2. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force.

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Smolen, Josef S, Breedveld, Ferdinand C, Burmester, Gerd R, Bykerk, Vivian, Dougados, Maxime, Emery, Paul, Kvien, Tore K, Navarro-Compán, M Victoria, Oliver, Susan, Schoels, Monika, Scholte-Voshaar, Marieke, Stamm, Tanja, Stoffer, Michaela, Takeuchi, Tsutomu, Aletaha, Daniel, Andreu, Jose Louis, Aringer, Martin, Bergman, Martin, Betteridge, Neil, Bijlsma, Hans, Burkhardt, Harald, Cardiel, Mario, Combe, Bernard, Durez, Patrick, Fonseca, Joao Eurico, Gibofsky, Alan, Gomez-Reino, Juan J, Graninger, Winfried, Hannonen, Pekka, Haraoui, Boulos, Kouloumas, Marios, Landewe, Robert, Martin-Mola, Emilio, Nash, Peter, Ostergaard, Mikkel, Östör, Andrew, Richards, Pam, Sokka-Isler, Tuulikki, Thorne, Carter, Tzioufas, Athanasios G, van Vollenhoven, Ronald, de Wit, Martinus, van der Heijde, Desirée, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Smolen, Josef S, Breedveld, Ferdinand C, Burmester, Gerd R, Bykerk, Vivian, Dougados, Maxime, Emery, Paul, Kvien, Tore K, Navarro-Compán, M Victoria, Oliver, Susan, Schoels, Monika, Scholte-Voshaar, Marieke, Stamm, Tanja, Stoffer, Michaela, Takeuchi, Tsutomu, Aletaha, Daniel, Andreu, Jose Louis, Aringer, Martin, Bergman, Martin, Betteridge, Neil, Bijlsma, Hans, Burkhardt, Harald, Cardiel, Mario, Combe, Bernard, Durez, Patrick, Fonseca, Joao Eurico, Gibofsky, Alan, Gomez-Reino, Juan J, Graninger, Winfried, Hannonen, Pekka, Haraoui, Boulos, Kouloumas, Marios, Landewe, Robert, Martin-Mola, Emilio, Nash, Peter, Ostergaard, Mikkel, Östör, Andrew, Richards, Pam, Sokka-Isler, Tuulikki, Thorne, Carter, Tzioufas, Athanasios G, van Vollenhoven, Ronald, de Wit, Martinus, and van der Heijde, Desirée

Abstract

BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. OBJECTIVE: To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. METHODS: A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. RESULTS: The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the di

Published
2016

3. Treating rheumatoid arthritis to target:2014 update of the recommendations of an international task force

Author

Smolen, Josef S, Breedveld, Ferdinand C, Burmester, Gerd R, Bykerk, Vivian, Dougados, Maxime, Emery, Paul, Kvien, Tore K, Navarro-Compán, M Victoria, Oliver, Susan, Schoels, Monika, Scholte-Voshaar, Marieke, Stamm, Tanja, Stoffer, Michaela, Takeuchi, Tsutomu, Aletaha, Daniel, Andreu, Jose Louis, Aringer, Martin, Bergman, Martin, Betteridge, Neil, Bijlsma, Hans, Burkhardt, Harald, Cardiel, Mario, Combe, Bernard, Durez, Patrick, Fonseca, Joao Eurico, Gibofsky, Alan, Gomez-Reino, Juan J, Graninger, Winfried, Hannonen, Pekka, Haraoui, Boulos, Kouloumas, Marios, Landewe, Robert, Martin-Mola, Emilio, Nash, Peter, Ostergaard, Mikkel, Östör, Andrew, Richards, Pam, Sokka-Isler, Tuulikki, Thorne, Carter, Tzioufas, Athanasios G, van Vollenhoven, Ronald, de Wit, Martinus, van der Heijde, Desirée, Smolen, Josef S, Breedveld, Ferdinand C, Burmester, Gerd R, Bykerk, Vivian, Dougados, Maxime, Emery, Paul, Kvien, Tore K, Navarro-Compán, M Victoria, Oliver, Susan, Schoels, Monika, Scholte-Voshaar, Marieke, Stamm, Tanja, Stoffer, Michaela, Takeuchi, Tsutomu, Aletaha, Daniel, Andreu, Jose Louis, Aringer, Martin, Bergman, Martin, Betteridge, Neil, Bijlsma, Hans, Burkhardt, Harald, Cardiel, Mario, Combe, Bernard, Durez, Patrick, Fonseca, Joao Eurico, Gibofsky, Alan, Gomez-Reino, Juan J, Graninger, Winfried, Hannonen, Pekka, Haraoui, Boulos, Kouloumas, Marios, Landewe, Robert, Martin-Mola, Emilio, Nash, Peter, Ostergaard, Mikkel, Östör, Andrew, Richards, Pam, Sokka-Isler, Tuulikki, Thorne, Carter, Tzioufas, Athanasios G, van Vollenhoven, Ronald, de Wit, Martinus, and van der Heijde, Desirée

Abstract

BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights.OBJECTIVE: To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion.METHODS: A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived.RESULTS: The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for part

Published
2016

4. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force

Author

Smolen, Josef S., Breedveld, Ferdinand C., Burmester, Gerd-Rüdiger, Bykerk, Vivian, Dougados, Maxime, Emery, Paul, Kvien, Tore K., Navarro-Compán, M. Victoria, Oliver, Susan, Schoels, Monika, Scholte-Voshaar, Marieke, Stamm, Tanja, Stoffer, Michaela, Takeuchi, Tsutomu, Aletaha, Daniel, Andreu, Jose Louis, Aringer, Martin, Bergman, Martin, Bijlsma, Hans, Burkhardt, Harald, Cardiel-Ríos, Mario Humberto, Combe, Bernard, Durez, Patrick, Fonseca, Joao Eurico, Gibofsky, Alan, Gomez-Reino, Juan J., Graninger, Winfried, Hannonen, Pekka, Haraoui, Boulos, Kouloumas, Marios, Landewe, Robert, Martin-Mola, Emilio, Nash, Peter, Ostergaard, Mikkel, Östör, Andrew, Richards, Pam, Sokka-Isler, Tuulikki, Thorne, Carter, Tzioufas, Athanasios G., Vollenhoven, Ronald van, Wit, Martinus de, Heijde, Désirée M. van der, Smolen, Josef S., Breedveld, Ferdinand C., Burmester, Gerd-Rüdiger, Bykerk, Vivian, Dougados, Maxime, Emery, Paul, Kvien, Tore K., Navarro-Compán, M. Victoria, Oliver, Susan, Schoels, Monika, Scholte-Voshaar, Marieke, Stamm, Tanja, Stoffer, Michaela, Takeuchi, Tsutomu, Aletaha, Daniel, Andreu, Jose Louis, Aringer, Martin, Bergman, Martin, Bijlsma, Hans, Burkhardt, Harald, Cardiel-Ríos, Mario Humberto, Combe, Bernard, Durez, Patrick, Fonseca, Joao Eurico, Gibofsky, Alan, Gomez-Reino, Juan J., Graninger, Winfried, Hannonen, Pekka, Haraoui, Boulos, Kouloumas, Marios, Landewe, Robert, Martin-Mola, Emilio, Nash, Peter, Ostergaard, Mikkel, Östör, Andrew, Richards, Pam, Sokka-Isler, Tuulikki, Thorne, Carter, Tzioufas, Athanasios G., Vollenhoven, Ronald van, Wit, Martinus de, and Heijde, Désirée M. van der

Abstract

Background Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. Objective To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. Methods A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. Results The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the diseas

Published
2015

5. Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alonso-Perez, Elisa, Suarez-Gestal, Marian, Calaza, Manuel, Blanco, Francisco J, Suarez, Ana, Santos, Maria Jose, Papasteriades, Chryssa, Carreira, Patricia, Pullmann, Rudolf, Ordi-Ros, Josep, Marchini, Maurizio, Skopouli, Fotini N, Bijl, Marc, Barrizone, Nadia, Sebastiani, Gian Domenico, Migliaresi, Sergio, Witte, Torsten, Lauwerys, Bernard, Kovacs, Attila, Ruzickova, Sarka, Gomez-Reino, Juan J, Gonzalez, Antonio, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alonso-Perez, Elisa, Suarez-Gestal, Marian, Calaza, Manuel, Blanco, Francisco J, Suarez, Ana, Santos, Maria Jose, Papasteriades, Chryssa, Carreira, Patricia, Pullmann, Rudolf, Ordi-Ros, Josep, Marchini, Maurizio, Skopouli, Fotini N, Bijl, Marc, Barrizone, Nadia, Sebastiani, Gian Domenico, Migliaresi, Sergio, Witte, Torsten, Lauwerys, Bernard, Kovacs, Attila, Ruzickova, Sarka, Gomez-Reino, Juan J, and Gonzalez, Antonio

Abstract

NTRODUCTION: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE. METHODS: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRS(s)). RESULTS: Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS(s). GRS(s) were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10(-16)) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10(-7)), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results. CONCLUSION: Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women.

Published
2014

6. Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study.

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alonso-Perez, Elisa, Suarez-Gestal, Marian, Calaza, Manuel, Ordi-Ros, Josep, Balada, Eva, Bijl, Marc, Papasteriades, Chryssa, Carreira, Patricia, Skopouli, Fotini N, Witte, Torsten, Endreffy, Emöke, Marchini, Maurizio, Migliaresi, Sergio, Sebastiani, Gian Domenico, Santos, Maria Jose, Suarez, Ana, Blanco, Francisco J, Barizzone, Nadia, Pullmann, Rudolf, Ruzickova, Sarka, Lauwerys, Bernard, Gomez-Reino, Juan J, Gonzalez, Antonio, European Consortium of SLE DNA Collections, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alonso-Perez, Elisa, Suarez-Gestal, Marian, Calaza, Manuel, Ordi-Ros, Josep, Balada, Eva, Bijl, Marc, Papasteriades, Chryssa, Carreira, Patricia, Skopouli, Fotini N, Witte, Torsten, Endreffy, Emöke, Marchini, Maurizio, Migliaresi, Sergio, Sebastiani, Gian Domenico, Santos, Maria Jose, Suarez, Ana, Blanco, Francisco J, Barizzone, Nadia, Pullmann, Rudolf, Ruzickova, Sarka, Lauwerys, Bernard, Gomez-Reino, Juan J, Gonzalez, Antonio, and European Consortium of SLE DNA Collections

Abstract

INTRODUCTION: Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question. METHODS: European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR) classification criteria (except ANAs) and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication. RESULTS: THERE WERE THREE NEW ASSOCIATIONS: the SNPs in XKR6 and in FAM167A-BLK were associated with lupus nephritis (OR=0.76 and 1.30, P(corr) =0.007 and 0.03, respectively) and the SNP of MECP2, which is in chromosome X, with earlier age of disease onset in men. The previously reported association of STAT4 with early age of disease onset was replicated. Some other results were suggestive of the presence of additional associations. Together, the association signals provided support to some previous findings and to the characterization of lupus nephritis, autoantibodies and age of disease onset as the clinical features more associated with SLE loci. CONCLUSION: Some of the SLE loci shape the disease phenotype in addition to increase susceptibility to SLE. This influence is more prominent for some clinical features than for others. However, results are only partially consistent between studies and subphenotype specific GWAS are needed to unravel their genetic component.

Published
2012

7. Bias in effect size of systemic lupus erythematosus susceptibility loci across Europe: a case-control study

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alonso-Perez, Elisa, Suarez-Gestal, Marian, Calaza, Manuel, Sebastiani, Gian Domenico, Pullmann, Rudolf, Papasteriades, Chryssa, Kovacs, Attila, Skopouli, Fotini N, Bijl, Marc, Suarez, Ana, the European Consortium of SLE DNA Collections, Marchini, Maurizio, Migliaresi, Sergio, Carreira, Patricia, Ordi-Ros, Joseph, Witte, Torsten, Ruzickova, Sarka, Santos, Maria Jose, Barizzone, Nadia, Blanco, Francisco J, Lauwerys, Bernard, Gomez-Reino, Juan J, Gonzalez, Antonio, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alonso-Perez, Elisa, Suarez-Gestal, Marian, Calaza, Manuel, Sebastiani, Gian Domenico, Pullmann, Rudolf, Papasteriades, Chryssa, Kovacs, Attila, Skopouli, Fotini N, Bijl, Marc, Suarez, Ana, the European Consortium of SLE DNA Collections, Marchini, Maurizio, Migliaresi, Sergio, Carreira, Patricia, Ordi-Ros, Joseph, Witte, Torsten, Ruzickova, Sarka, Santos, Maria Jose, Barizzone, Nadia, Blanco, Francisco J, Lauwerys, Bernard, Gomez-Reino, Juan J, and Gonzalez, Antonio

Abstract

Introduction: We aimed to investigate whether the effect size of the systemic lupus erythematosus (SLE) risk alleles varies across European subpopulations.Methods: European SLE patients (n = 1,742) and ethnically matched healthy controls (n = 2,101) were recruited at 17 centres from 10 different countries. Only individuals with self-reported ancestry from the country of origin were included. In addition, participants were genotyped for top ancestry informative markers and for 25 SLE associated SNPs. The results were used to compare effect sizes between the Central Eureopan and Southern European subgroups.Results: Twenty of the 25 SNPs showed independent association with SLE, These SNPs showed a significant bias to larger effect sizes in the Southern subgroup, with 15/20 showing this trend (P = 0.019) and a larger mean odds ratio of the 20 SNPs (1.46 vs. 1.34, P = 0.02) as well as a larger difference in the number of risk alleles (2.06 vs. 1.63, P = 0.027) between SLE patients and controls than for Central Europeans. This bias was reflected in a very significant difference in the cumulative genetic risk score (4.31 vs. 3.48, P = 1.8 × 10 -32). Effect size bias was accompanied by a lower number of SLE risk alleles in the Southern subjects, both patients and controls, the difference being more marked between the controls (P = 1.1 × 10 -8) than between the Southern and Central European patients (P = 0.016). Seven of these SNPs showed significant allele frequency clines.Conclusion: Our findings showed a bias to larger effect sizes of SLE loci in the Southern Europeans relative to the Central Europeans together with clines of SLE risk allele frequencies. These results indicate the need to study risk allele clines and the implications of the polygenic model of inheritance in SLE. © 2012 Alonso-Perez et al.; licensee BioMed Central Ltd.

Published
2012

8. Seropositivity and response to RTX: Data from the CERERRA collaboration.

Author

Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, Van Riel, Piet L.C.M., Gomez-Reino, Juan J., Kvien, Tore K., van Vollenhoven, Ronald F., Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, Van Riel, Piet L.C.M., Gomez-Reino, Juan J., Kvien, Tore K., and van Vollenhoven, Ronald F.

Published
2011

9. Efficacy of different doses of rituximab for the treatment of rheumatoid arthritis: Data from the CERERRA collaboration.

Author

Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, van Riel, Piet L.C., Gomez-Reino, Juan J., Kvien, Tore K., van Vollenhoven, Ronald F., Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, van Riel, Piet L.C., Gomez-Reino, Juan J., Kvien, Tore K., and van Vollenhoven, Ronald F.

Published
2011

10. Early versus delayed retreatment with rituximab (RTX) in relation to long term clinical response - Data from the CERERRA collaboration.

Author

Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, van Vollenhoven, Ronald F., Kvien, Tore K., Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, van Vollenhoven, Ronald F., and Kvien, Tore K.

Published
2011

11. Characterization of long-term responders to first treatment course of rituximab (RTX) - Results from the CERERRA collaboration.

Author

Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, Kvien, Tore K., van Vollenhoven, Ronald F., Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, Kvien, Tore K., and van Vollenhoven, Ronald F.

Published
2011

12. Seropositivity and response to RTX: Data from the CERERRA collaboration.

Author

Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, Van Riel, Piet L.C.M., Gomez-Reino, Juan J., Kvien, Tore K., van Vollenhoven, Ronald F., Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, Van Riel, Piet L.C.M., Gomez-Reino, Juan J., Kvien, Tore K., and van Vollenhoven, Ronald F.

Published
2011

13. Efficacy of different doses of rituximab for the treatment of rheumatoid arthritis: Data from the CERERRA collaboration.

Author

Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, van Riel, Piet L.C., Gomez-Reino, Juan J., Kvien, Tore K., van Vollenhoven, Ronald F., Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, van Riel, Piet L.C., Gomez-Reino, Juan J., Kvien, Tore K., and van Vollenhoven, Ronald F.

Published
2011

14. Early versus delayed retreatment with rituximab (RTX) in relation to long term clinical response - Data from the CERERRA collaboration.

Author

Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, van Vollenhoven, Ronald F., Kvien, Tore K., Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, van Vollenhoven, Ronald F., and Kvien, Tore K.

Published
2011

15. Characterization of long-term responders to first treatment course of rituximab (RTX) - Results from the CERERRA collaboration.

Author

Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, Kvien, Tore K., van Vollenhoven, Ronald F., Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, Kvien, Tore K., and van Vollenhoven, Ronald F.

Published
2011

16. Seropositivity and response to RTX: Data from the CERERRA collaboration.

Author

Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, Van Riel, Piet L.C.M., Gomez-Reino, Juan J., Kvien, Tore K., van Vollenhoven, Ronald F., Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, Van Riel, Piet L.C.M., Gomez-Reino, Juan J., Kvien, Tore K., and van Vollenhoven, Ronald F.

Published
2011

17. Early versus delayed retreatment with rituximab (RTX) in relation to long term clinical response - Data from the CERERRA collaboration.

Author

Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, van Vollenhoven, Ronald F., Kvien, Tore K., Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, van Vollenhoven, Ronald F., and Kvien, Tore K.

Published
2011

18. Efficacy of different doses of rituximab for the treatment of rheumatoid arthritis: Data from the CERERRA collaboration.

Author

Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, van Riel, Piet L.C., Gomez-Reino, Juan J., Kvien, Tore K., van Vollenhoven, Ronald F., Chatzidionysiou, Katerina, Lie, Elisabeth, Nasonov, Evgeny L., Lukina, Galina, Hetland, Merete Lund, Tarp, Ulrik, Ancuta, Ioan, Pavelka, Karel, Nordström, Dan C., Gabay, Cem, Canhao, Helena, Tomsic, Matija, van Riel, Piet L.C., Gomez-Reino, Juan J., Kvien, Tore K., and van Vollenhoven, Ronald F.

Published
2011

19. Characterization of long-term responders to first treatment course of rituximab (RTX) - Results from the CERERRA collaboration.

Author

Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, Kvien, Tore K., van Vollenhoven, Ronald F., Lie, Elisabeth, Chatzidionysiou, Katerina, Nasonov, Evgeny L., Lukina, Galina, Pavelka, Karel, Nordström, Dan C., Tomsic, Matija, Gabay, Cem, Ancuta, Ioan, van Riel, Piet L.C., Gomez-Reino, Juan J., Fonseca, João E., Hetland, Merete Lund, Tarp, Ulrik, Kvien, Tore K., and van Vollenhoven, Ronald F.

Published
2011

20. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis.

Author

UCL - (SLuc) Service de rhumatologie, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, Hueber, Wolfgang, Patel, Dhavalkumar D, Dryja, Thaddeus, Wright, Andrew M, Koroleva, Irina, Bruin, Gerard, Antoni, Christian, Draelos, Zoe, Gold, Michael H, Durez, Patrick, Tak, Paul P, Gomez-Reino, Juan J, Foster, C Stephen, Kim, Rosa Y, Samson, C Michael, Falk, Naomi S, Chu, David S, Callanan, David, Nguyen, Quan Dong, Rose, Kristine, Haider, Asifa, Di Padova, Franco, UCL - (SLuc) Service de rhumatologie, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, Hueber, Wolfgang, Patel, Dhavalkumar D, Dryja, Thaddeus, Wright, Andrew M, Koroleva, Irina, Bruin, Gerard, Antoni, Christian, Draelos, Zoe, Gold, Michael H, Durez, Patrick, Tak, Paul P, Gomez-Reino, Juan J, Foster, C Stephen, Kim, Rosa Y, Samson, C Michael, Falk, Naomi S, Chu, David S, Callanan, David, Nguyen, Quan Dong, Rose, Kristine, Haider, Asifa, and Di Padova, Franco

Abstract

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.

Published
2010

21. Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

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.

Abstract

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MR

22. Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Author

Fleischmann, Roy, van Vollenhoven, Ronald F., Smolen, Josef, Emery, Paul, Florentinus, Stefan, Rathmann, Suchitrita, Kupper, Hartmut, Kavanaugh, Arthur, Taylor, Peter, Genovese, Mark, Keystone, Edward C., Drescher, Edit, Berclaz, Pierre-Yves, Lee, Chin, Fidelus-Gort, Rosalind, Schlichting, Douglas, Beattie, Scott, Luchi, Monica, Macias, William, Dikranian, Ara H., Alten, Rieke, Klearman, Micki, Musselman, David, Agarwal, Sunil, Green, Jennifer, Gabay, Cem, Weinblatt, Michael E., Schiff, Michael H., Valente, Robert, van der Heijde, Desiree, Citera, Gustavo, Zhao, Cathy, Maldonado, Michael A., Rakieh, Chadi, Nam, Jacqueline L., Hunt, Laura, Villeneuve, Edith, Bissell, Lesley-Anne, Das, Sudipto, Conaghan, Philip, McGonagle, Dennis, Wakefield, Richard J., Wright, Helen L., Thomas, Huw B., Moots, Robert, Edwards, Steven W., Hamann, Philip, Heward, James, McHugh, Neil, Lindsay, Mark A., Haroon, Muhammad, Giles, Jon T., Winchester, Robert, FitzGerald, Oliver, Karaderi, Tugce, Cohen, Carla J., Keidel, Sarah, Appleton, Louise H., Macfarlane, Gary J., Siebert, Stefan, Evans, David, Paul Wordsworth, B., Plant, Darren, Bowes, John, Orozco, Gisela, Morgan, Ann W., Wilson, Anthony G., Isaacs, John, Barton, Anne, Williams, Frances M., Livshits, Gregory, Spector, Tim, MacGregor, Alexander, Scollen, Serena, Cao, Dandan, Memari, Yasin, Hyde, Craig L., Zhang, Baohong, Sidders, Benjamin, Ziemek, Daniel, Shi, Yujian, Harris, Juliette, Harrow, Ian, Dougherty, Brian, Malarstig, Anders, McEwen, Robert, Stephens, Joel L., Patel, Ketan, Shin, So-Youn, Surdulescu, Gabriela, He, Wen, Jin, Xin, McMahon, Stephen B., Soranzo, Nicole, John, Sally, Wang, Jun, Spector, Tim D., Baker, Jonathan, Litherland, Gary J., Rowan, Andrew D., Kite, Kerry A., Bayley, Rachel, Yang, Peiming, Smith, Jacqueline P., Williams, Julie, Harper, Lorraine, Kitas, George D., Buckley, Christopher, Young, Stephen P., Fitzpatrick, Martin A., McGettrick, Helen M., Filer, Andrew, Raza, Karim, Nash, Gerard, Muthana, Munitta, Davies, Holly, Khetan, Sachin, Adeleke, Gbadebo, Hawtree, Sarah, Tazzyman, Simon, Morrow, Fiona, Ciani, Barbara, Wilson, Gerry, Quirke, Anne-Marie, Lugli, Elena, Wegner, Natalia, Charles, Peter, Hamilton, Bart, Chowdhury, Muslima, Ytterberg, Jimmy, Potempa, Jan, Fisher, Benjamin, Thiele, Geoffrey, Mikuls, Ted, Venables, Patrick, Adebajo, Adewale O., Mease, Philip, Gomez-Reino, Juan J., Wollenhaupt, Jurgen, Hu, ChiaChi, Stevens, Randall, Sieper, Joachim, Dougados, Maxime, Van den Bosch, Filip, Goupille, Philippe, Rathmann, Suchitrita S., Pangan, Aileen L., Maksymowych, Walter P., Brown, Matthew A., Elewaut, Dirk, Anderson, Jaclyn, Ramasamy, Pathma, O'Rourke, Michael, Murphy, Conor, Fitzgerald, Oliver, Jani, Meghna, Moore, Sarah, Mirjafari, Hoda, Macphie, Elizabeth, Chinoy, Hector, Rao, Chan, McLoughlin, Yokemei, Preeti, Shah, Fleischmann, Roy, van Vollenhoven, Ronald F., Smolen, Josef, Emery, Paul, Florentinus, Stefan, Rathmann, Suchitrita, Kupper, Hartmut, Kavanaugh, Arthur, Taylor, Peter, Genovese, Mark, Keystone, Edward C., Drescher, Edit, Berclaz, Pierre-Yves, Lee, Chin, Fidelus-Gort, Rosalind, Schlichting, Douglas, Beattie, Scott, Luchi, Monica, Macias, William, Dikranian, Ara H., Alten, Rieke, Klearman, Micki, Musselman, David, Agarwal, Sunil, Green, Jennifer, Gabay, Cem, Weinblatt, Michael E., Schiff, Michael H., Valente, Robert, van der Heijde, Desiree, Citera, Gustavo, Zhao, Cathy, Maldonado, Michael A., Rakieh, Chadi, Nam, Jacqueline L., Hunt, Laura, Villeneuve, Edith, Bissell, Lesley-Anne, Das, Sudipto, Conaghan, Philip, McGonagle, Dennis, Wakefield, Richard J., Wright, Helen L., Thomas, Huw B., Moots, Robert, Edwards, Steven W., Hamann, Philip, Heward, James, McHugh, Neil, Lindsay, Mark A., Haroon, Muhammad, Giles, Jon T., Winchester, Robert, FitzGerald, Oliver, Karaderi, Tugce, Cohen, Carla J., Keidel, Sarah, Appleton, Louise H., Macfarlane, Gary J., Siebert, Stefan, Evans, David, Paul Wordsworth, B., Plant, Darren, Bowes, John, Orozco, Gisela, Morgan, Ann W., Wilson, Anthony G., Isaacs, John, Barton, Anne, Williams, Frances M., Livshits, Gregory, Spector, Tim, MacGregor, Alexander, Scollen, Serena, Cao, Dandan, Memari, Yasin, Hyde, Craig L., Zhang, Baohong, Sidders, Benjamin, Ziemek, Daniel, Shi, Yujian, Harris, Juliette, Harrow, Ian, Dougherty, Brian, Malarstig, Anders, McEwen, Robert, Stephens, Joel L., Patel, Ketan, Shin, So-Youn, Surdulescu, Gabriela, He, Wen, Jin, Xin, McMahon, Stephen B., Soranzo, Nicole, John, Sally, Wang, Jun, Spector, Tim D., Baker, Jonathan, Litherland, Gary J., Rowan, Andrew D., Kite, Kerry A., Bayley, Rachel, Yang, Peiming, Smith, Jacqueline P., Williams, Julie, Harper, Lorraine, Kitas, George D., Buckley, Christopher, Young, Stephen P., Fitzpatrick, Martin A., McGettrick, Helen M., Filer, Andrew, Raza, Karim, Nash, Gerard, Muthana, Munitta, Davies, Holly, Khetan, Sachin, Adeleke, Gbadebo, Hawtree, Sarah, Tazzyman, Simon, Morrow, Fiona, Ciani, Barbara, Wilson, Gerry, Quirke, Anne-Marie, Lugli, Elena, Wegner, Natalia, Charles, Peter, Hamilton, Bart, Chowdhury, Muslima, Ytterberg, Jimmy, Potempa, Jan, Fisher, Benjamin, Thiele, Geoffrey, Mikuls, Ted, Venables, Patrick, Adebajo, Adewale O., Mease, Philip, Gomez-Reino, Juan J., Wollenhaupt, Jurgen, Hu, ChiaChi, Stevens, Randall, Sieper, Joachim, Dougados, Maxime, Van den Bosch, Filip, Goupille, Philippe, Rathmann, Suchitrita S., Pangan, Aileen L., Maksymowych, Walter P., Brown, Matthew A., Elewaut, Dirk, Anderson, Jaclyn, Ramasamy, Pathma, O'Rourke, Michael, Murphy, Conor, Fitzgerald, Oliver, Jani, Meghna, Moore, Sarah, Mirjafari, Hoda, Macphie, Elizabeth, Chinoy, Hector, Rao, Chan, McLoughlin, Yokemei, and Preeti, Shah

Abstract

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the

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