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202. THU0071 THE COMBINATION OF RHEUMATOID FACTORS WITH ANTIBODY SYSTEMS TARGETING CITRULLINATED, CARBAMYLATED AND PEPTIDYL ARGININE DEIMINASE AUTOANTIGENS DISTINGUISHES RHEUMATOID ARTHRITIS

Author

Dervieux, Thierry, primary, Conklin, John, additional, O’malley, Tyler, additional, Brady, Kelley, additional, Alexander, Roberta, additional, Shi, Jing, additional, Ibarra, Claudia, additional, Mahler, Michael, additional, Kremer, Joel, additional, Weinblatt, Michael E., additional, and Weinstein, Arthur, additional

Published
2019
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203. THU0065 VALIDATION OF THE ADJUSTED MULTI-BIOMARKER DISEASE ACTIVITY SCORE FOR PREDICTING RISK OF RADIOGRAPHIC PROGRESSION FOR PATIENTS WITH RHEUMATOID ARTHRITIS

Author

Curtis, Jeffrey R., primary, Weinblatt, Michael E., additional, Shadick, Nancy, additional, Brahe, Cecilie Heegaard, additional, Ǿstergaard, Mikkel, additional, Hetland, Merete L., additional, Saevarsdottir, Saedis, additional, Horton, Megan, additional, Mabey, Brent, additional, Flake, Darl, additional, Sasso, Eric H., additional, and Huizinga, Thomas, additional

Published
2019
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205. OP0122 EXPLORING HETEROGENEITY IN RHEUMATOID ARTHRITIS: PATIENT PROFILING THROUGH PRINCIPAL COMPONENT AND CLUSTER ANALYSIS OF THE BRASS REGISTRY

Author

Curtis, Jeffrey R., primary, Weinblatt, Michael E., additional, Saag, Kenneth, additional, Bykerk, Vivian, additional, Charles-Schoeman, Christina, additional, Fiore, Stefano, additional, John, Gregory St., additional, Kimura, Toshio, additional, Zheng, Shen, additional, Bingham, Clifton, additional, Wright, Grace, additional, Bergman, Martin, additional, Nola, Kamala, additional, Furst, Daniel E., additional, and Shadick, Nancy, additional

Published
2019
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206. Cardiovascular Safety During Treatment With Baricitinib in Rheumatoid Arthritis

Author

Taylor, Peter C., primary, Weinblatt, Michael E., additional, Burmester, Gerd R., additional, Rooney, Terence P., additional, Witt, Sarah, additional, Walls, Chad D., additional, Issa, Maher, additional, Salinas, Claudia A., additional, Saifan, Chadi, additional, Zhang, Xin, additional, Cardoso, Anabela, additional, González‐Gay, Miguel A., additional, and Takeuchi, Tsutomu, additional

Published
2019
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209. Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for CD40 and CD39

Author

Spiliopoulou, Athina, primary, Colombo, Marco, additional, Plant, Darren, additional, Nair, Nisha, additional, Cui, Jing, additional, Coenen, Marieke JH, additional, Ikari, Katsunori, additional, Yamanaka, Hisashi, additional, Saevarsdottir, Saedis, additional, Padyukov, Leonid, additional, Bridges Jr., S Louis, additional, Kimberly, Robert P, additional, Okada, Yukinori, additional, van Riel, Piet L CM, additional, Wolbink, Gertjan, additional, van der Horst-Bruinsma, Irene E, additional, de Vries, Niek, additional, Tak, Paul P, additional, Ohmura, Koichiro, additional, Canhão, Helena, additional, Guchelaar, Henk-Jan, additional, Huizinga, Tom WJ, additional, Criswell, Lindsey A, additional, Raychaudhuri, Soumya, additional, Weinblatt, Michael E, additional, Wilson, Anthony G, additional, Mariette, Xavier, additional, Isaacs, John D, additional, Morgan, Ann W, additional, Pitzalis, Costantino, additional, Barton, Anne, additional, and McKeigue, Paul, additional

Published
2019
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210. Prevalence and predictors for sustained remission in rheumatoid arthritis

Author

Sung, Yoon-Kyoung, primary, Yoshida, Kazuki, additional, Prince, Femke H. M., additional, Frits, Michelle L., additional, Cho, Soo-Kyung, additional, Choe, Jung-Yoon, additional, Lee, Hye-Soon, additional, Lee, Jisoo, additional, Lee, Shin-Seok, additional, Yoo, Dae-Hyun, additional, Helfgott, Simon M., additional, Shadick, Nancy A., additional, Weinblatt, Michael E., additional, Solomon, Daniel H., additional, and Bae, Sang-Cheol, additional

Published
2019
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212. Incidence and Predictors of Dyspnea on Exertion in a Prospective Cohort of Patients With Rheumatoid Arthritis

Author

Sparks, Jeffrey A., primary, Doyle, Tracy J., additional, He, Xintong, additional, Pan, Beatrice, additional, Iannaccone, Christine, additional, Frits, Michelle L., additional, Dellaripa, Paul F., additional, Rosas, Ivan O., additional, Lu, Bing, additional, Weinblatt, Michael E., additional, Shadick, Nancy A., additional, and Karlson, Elizabeth W., additional

Published
2019
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213. Adjustment of the multi-biomarker disease activity score to account for age, sex and adiposity in patients with rheumatoid arthritis

Author

Curtis, Jeffrey R, primary, Flake, Darl D, additional, Weinblatt, Michael E, additional, Shadick, Nancy A, additional, Østergaard, Mikkel, additional, Hetland, Merete Lund, additional, Brahe, Cecilie Heegaard, additional, Hwang, Yong Gil, additional, Furst, Daniel E, additional, Strand, Vibeke, additional, Etzel, Carol J, additional, Pappas, Dimitrios A, additional, Wang, Xingbin, additional, Hwang, Ching Chang, additional, Sasso, Eric H, additional, Gutin, Alexander, additional, Hitraya, Elena, additional, and Lanchbury, Jerry S, additional

Published
2018
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217. Lifestyle and Clinical Risk Factors for Incident Rheumatoid Arthritis-associated Interstitial Lung Disease.

Author

Kronzer, Vanessa L., Weixing Huang, Dellaripa, Paul F., Sicong Huang, Feathers, Vivi, Bing Lu, Iannaccone, Christine K., Gill, Ritu R., Hiroto Hatabu, Mizuki Nishino, Crowson, Cynthia S., Davis III, John M., Weinblatt, Michael E., Shadick, Nancy A., Doyle, Tracy J., Sparks, Jeffrey A., Huang, Weixing, Huang, Sicong, Lu, Bing, and Hatabu, Hiroto

Published
2021
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227. Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis

Author

Kjelgaard-Petersen, Cecilie Freja, Platt, Adam, Braddock, Martin, Jenkins, Martin A., Musa, Kishwar, Graham, Emma, Gantzel, Thorbjorn, Slynn, Gillian, Weinblatt, Michael E., Karsdal, Morten A., Thudium, Christian S., Bay-Jensen, Anne-C, Kjelgaard-Petersen, Cecilie Freja, Platt, Adam, Braddock, Martin, Jenkins, Martin A., Musa, Kishwar, Graham, Emma, Gantzel, Thorbjorn, Slynn, Gillian, Weinblatt, Michael E., Karsdal, Morten A., Thudium, Christian S., and Bay-Jensen, Anne-C

Abstract

Objective. Rheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to disability, reduced quality of life, and increased mortality. Although several synthetic and biologic disease-modifying antirheumatic drugs are available, there is still a medical need for novel drugs that control disease progression. As only 10% of experimental drug candidates for treatment of RA that enter phase I trials are eventually registered by the Food and Drug Administration, there is an immediate need for translational tools to facilitate early decision-making in drug development. In this study, we aimed to determine if the inability of fostamatinib (a small molecule inhibitor of Syk) to demonstrate sufficient efficacy in phase III of a previous clinical study could have been predicted earlier in the development process.Methods. Biomarkers of bone, cartilage, and interstitial matrix turnover (C-telopeptide of type I collagen [CTX-I], matrix metalloproteinase-derived types I, II, and III collagen neoepitopes [C1M, C2M, and C3M]) were measured in 450 serum samples from the Oral Syk Inhibition in Rheumatoid Arthritis 1 study (OSKIRA-1, a phase III clinical study of the efficacy of fostamatinib in RA) at baseline and follow-up. Additionally, the same biomarkers were subsequently measured in conditioned media from osteoclast, cartilage, and synovial membrane cultured with the active metabolite of fostamatinib, R406, to assess the level of suppression induced by the drug.Results. In OSKIRA-1 serum samples and osteoclast and cartilage cultures, fostamatinib suppressed the levels of CTX-I and C2M. In OSKIRA-1 serum samples and synovial membrane cultures, fostamatinib did not mediate any clinical or preclinical effect on either C1M or C3M, which have previously been associated with disease response and efficacy.Conclusion. These data demonstrate that translational biomarkers are a potential tool for early assessment and decision-making in drug development for R

Published
2018

228. American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID‐19 Pandemic: Version 3.

Author

Mikuls, Ted R., Johnson, Sindhu R., Fraenkel, Liana, Arasaratnam, Reuben J., Baden, Lindsey R., Bermas, Bonnie L., Chatham, Winn, Cohen, Stanley, Costenbader, Karen, Gravallese, Ellen M., Kalil, Andre C., Weinblatt, Michael E., Winthrop, Kevin, Mudano, Amy S., Turner, Amy, and Saag, Kenneth G.

Subjects
RHEUMATISM treatment, CONSENSUS (Social sciences), DELPHI method, RHEUMATOLOGISTS, DISEASE management, COVID-19 pandemic, ADULTS
Abstract

Objective: To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID‐19) pandemic. Methods: A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly generated and disseminated. Questions and drafted statements were reviewed and assessed using a modified Delphi process. This included asynchronous anonymous voting by email and webinars with the entire panel. Task force members voted on agreement with draft statements using a 1–9‐point numerical scoring system, and consensus was determined to be low, moderate, or high based on the dispersion of votes. For approval, median votes were required to meet predefined levels of agreement (median values of 7–9, 4–6, and 1–3 defined as agreement, uncertainty, or disagreement, respectively) with either moderate or high levels of consensus. Results: Draft guidance statements approved by the task force have been combined to form final guidance. Conclusion: These guidance statements are provided to promote optimal care during the current pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a "living document," and future updates are anticipated. [ABSTRACT FROM AUTHOR]

Published
2021
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230. Fibromyalgia Predicts Two-Year Changes in Functional Status in Rheumatoid Arthritis Patients

Author

Kim, Hyein, Cui, Jing, Frits, Michelle, Iannaccone, Christine, Coblyn, Jonathan, Shadick, Nancy A., Weinblatt, Michael E., and Lee, Yvonne C.

Subjects
Male, Fibromyalgia, Time Factors, Health Status, Middle Aged, Prognosis, Severity of Illness Index, Article, Arthritis, Rheumatoid, Surveys and Questionnaires, Multivariate Analysis, Disease Progression, Linear Models, Humans, Female, Prospective Studies, Aged, Pain Measurement
Abstract

Previous cross-sectional studies have shown that rheumatoid arthritis (RA) patients with fibromyalgia (FM) have higher disease activity, greater medical costs, and worse quality of life compared to RA patients without FM. We determined the impact of FM on 2-year changes in the functional status of RA patients in a prospective study.Subjects included participants in the Brigham Rheumatoid Arthritis Sequential Study who were enrolled in a substudy of the effects of pain in RA. Subjects completed questionnaires, including the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) and Polysymptomatic Distress (PSD) scale, semiannually, and underwent physical examination and laboratory tests yearly.Of the 156 included RA subjects, 16.7% had FM, while 83.3% did not. In a multivariable linear regression model adjusted for age, sex, race, baseline MDHAQ score, disease duration, rheumatoid factor/cyclic citrullinated peptide antibody seropositivity, disease activity, and psychological distress, RA patients with FM had a 0.14 greater 2-year increase in MDHAQ score than RA patients without FM (P = 0.021). In secondary analyses examining the association between continuous PSD scale score and change in MDHAQ, higher PSD scale scores were significantly associated with greater 2-year increases in MDHAQ score (β coefficient 0.013, P = 0.011).Both the presence of FM and increasing number of FM symptoms predicted worsening of functional status among individuals with RA. Among individuals with RA and FM, the magnitude of the difference in changes in MDHAQ was 4- to 7-fold higher than typical changes in MDHAQ score among individuals with established RA.

Published
2017

231. Herpes Zoster in Patients with Moderate to Severe Rheumatoid Arthritis Treated with Baricitinib

Author

Winthrop, Kevin, Lindsey, SM, Weinblatt, Michael E., Takeuchi, Tsutomu, Hyslop, David, Issa, Maher, Chen, Lei, Dickson, Christina, Bradley, John, Fleischmann, R, and Steinmüller, Christina

Subjects
musculoskeletal diseases, stomatognathic diseases, ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Compared to the general population, rheumatoid arthritis (RA) patients (pts) have increased risk of herpes zoster (HZ), that is associated with various biologic DMARDs and JAK inhibitors. The aim of this analysis was to evaluate HZ in RA pts treated with baricitinib (bari), an oral JAK1/JAK2[for full text, please go to the a.m. URL], 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Published
2017
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232. 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, and Vital, Edward M.

Subjects
cardiovascular system
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 MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interest

Published
2017

233. The Patient Perspective

Author

de Wit, MPT, Hochberg, Marc C., Gravallese, Ellen M., Silman, Alan J., Smolen, Josef S., Weinblatt, Michael E., Weisman, Michael H., AII - Inflammatory diseases, and Ethics, Law & Medical humanities

Published
2017

234. Drug therapy in rheumatoid arthritis

Author

Kaplan, Herbert, Weinblatt, Michael E., and Wilder, Ronald L.

Subjects
Rheumatoid arthritis -- Drug therapy, Health, Drug therapy
Abstract

1 Today's pharmacologic strategies in rheumatoid arthritis are based on early intervention. This discussion of drug options-- and the recommended monitoring--will make your 'choices easier, EXPRESS STOP Early intervention: Rheumatologists [...]

Published
1992

235. Inhibition of leukotriene B4 synthesis in neutrophils from patients with rheumatoid arthritis by a single oral dose of methotrexate

Author

Sperling, Richard I., Coblyn, Jonathan S., Larkin, John K., Benincaso, Anthony I., Austen, K. Frank, and Weinblatt, Michael E.

Subjects
Methotrexate -- Physiological aspects, Rheumatoid arthritis -- Drug therapy, Health
Abstract

Methotrexate (MTX) is a drug originally used to treat cancer, but in low doses, it has been an effective treatment for rheumatoid arthritis (RA). RA is an autoimmune disease, which occurs when the body inappropriately makes antibodies against its own tissues. The basis for the effect of MTX on RA has been attributed to cytotoxic (cell-killing) effects on immune cells, since high doses of MTX suppress immune function. However, other studies indicate that low-dose MTX may act by decreasing inflammatory processes in the body. To better the establish the basis of MTX action in RA, the effects of MTX on neutrophils (inflammation-linked white blood cells) from six RA patients were evaluated. Neutrophil production of leukotriene B4 (LTB4), an inflammatory agent produced from the dietary fatty acid arachidonic acid, was significantly decreased in patients after MTX treatment. This was not due to increased breakdown of LTB4. Rather, one or more of the enzymes that change arachidonic acid into LTB4 is apparently inhibited by MTX. Further research is needed to determine if these processes are involved in the therapeutic effect of MTX in patients with RA. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

236. Low-dose methotrexate compared with auranofin in adult rheumatoid arthritis: a thirty-six-week, double-blind trial

Author

Weinblatt, Michael E., Kaplan, Herbert, Germain, Bernard F., Merriman, Richard C., Solomon, Sheldon D., Wall, Bruce, Anderson, Larry, Block, Sidney, Irby, Robert, Wolfe, Frederick, Gall, Eric, Torretti, Dennis, Biundo, Joseph, Small, Ralph, Coblyn, Jon, and Polisson, Richard

Subjects
Antirheumatic agents -- Evaluation, Methotrexate -- Evaluation, Rheumatoid arthritis -- Drug therapy, Health
Abstract

Several studies have shown that the drug methotrexate is effective in treating rheumatoid arthritis, an inflammatory joint disease, particularly in patients who are not responsive to conventional therapy. Methotrexate treatment is associated with sustained effectiveness, a decrease in the dose of corticosteroids needed to counteract inflammation, tolerable levels of toxicity, and improved measures of disease severity, such as the erythrocyte sedimentation rate. Studies have shown that methotrexate is more effective and causes more rapid improvement than another agent, azathioprine, used to treat rheumatoid arthritis. The effectiveness of methotrexate was compared with that of the drug auranofin in 281 patients with active rheumatoid arthritis over a 36-week period. Both drugs were effective in treating rheumatoid arthritis, although the effect of methotrexate was greater and occurred earlier than that of auranofin. Methotrexate caused significantly greater improvement in terms of alleviating pain and swelling of joints and reducing disease activity, as assessed by patients and physicians. Auranofin caused more adverse effects and a greater frequency of patients withdrawing from the study due to toxicity of the drug. The findings suggest that methotrexate is more effective and better tolerated than auranofin. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

237. Unmet need in rheumatology: reports from the Targeted Therapies meeting 2019.

Author

Winthrop, Kevin L., Weinblatt, Michael E., Bathon, Joan, Burmester, Gerd R., Mease, Philip J., Crofford, Leslie, Bykerk, Vivian, Dougados, Maxime, Rosenbaum, James Todd, Mariette, Xavier, Sieper, Joachim, Melchers, Fritz, Cronstein, Bruce N., Breedveld, Ferry C., Kalden, Joachim, Smolen, Josef S., and Furst, Daniel

Subjects
DRUG therapy for rheumatism, EXPERIMENTAL design, PSORIATIC arthritis, RESEARCH, CLINICAL trials, NEUROPHYSIOLOGY, ANKYLOSING spondylitis, RHEUMATOLOGY, CONFERENCES & conventions, DRUG therapy, RHEUMATOID arthritis, SYSTEMIC lupus erythematosus, NEEDS assessment, RHEUMATISM, MEDICAL research
Abstract

Objectives: To detail the greatest areas of unmet scientific and clinical needs in rheumatology.Methods: The 21st annual international Advances in Targeted Therapies meeting brought together more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. During the meeting, breakout sessions were convened, consisting of 5 disease-specific groups with 20-30 experts assigned to each group based on expertise. Specific groups included: rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus and other systemic autoimmune rheumatic diseases. In each group, experts were asked to identify unmet clinical and translational research needs in general and then to prioritise and detail the most important specific needs within each disease area.Results: Overarching themes across all disease states included the need to innovate clinical trial design with emphasis on studying patients with refractory disease, the development of trials that take into account disease endotypes and patients with overlapping inflammatory diseases, the need to better understand the prevalence and incidence of inflammatory diseases in developing regions of the world and ultimately to develop therapies that can cure inflammatory autoimmune diseases.Conclusions: Unmet needs for new therapies and trial designs, particularly for those with treatment refractory disease, remain a top priority in rheumatology. [ABSTRACT FROM AUTHOR]

Published
2020
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238. 56 - Metotrexato

Author

JOHNSEN, ALYSSA K. and WEINBLATT, MICHAEL E.

Published
2016

239. Phase II Study of ABT‐122, a Tumor Necrosis Factor– and Interleukin‐17A–Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate

Author

Mease, Philip J., primary, Genovese, Mark C., additional, Weinblatt, Michael E., additional, Peloso, Paul M., additional, Chen, Kun, additional, Othman, Ahmed A., additional, Li, Yihan, additional, Mansikka, Heikki T., additional, Khatri, Amit, additional, Wishart, Neil, additional, and Liu, John, additional

Published
2018
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240. Mixed-effects association of single cells identifies an expanded effector CD4 + T cell subset in rheumatoid arthritis

Author

Fonseka, Chamith Y., primary, Rao, Deepak A., additional, Teslovich, Nikola C., additional, Korsunsky, Ilya, additional, Hannes, Susan K., additional, Slowikowski, Kamil, additional, Gurish, Michael F., additional, Donlin, Laura T., additional, Lederer, James A., additional, Weinblatt, Michael E., additional, Massarotti, Elena M., additional, Coblyn, Jonathan S., additional, Helfgott, Simon M., additional, Todd, Derrick J., additional, Bykerk, Vivian P., additional, Karlson, Elizabeth W., additional, Ermann, Joerg, additional, Lee, Yvonne C., additional, Brenner, Michael B., additional, and Raychaudhuri, Soumya, additional

Published
2018
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241. ABT ‐122, a Bispecific Dual Variable Domain Immunoglobulin Targeting Tumor Necrosis Factor and Interleukin‐17A, in Patients With Rheumatoid Arthritis With an Inadequate Response to Methotrexate

Author

Genovese, Mark C., primary, Weinblatt, Michael E., additional, Aelion, Jacob A., additional, Mansikka, Heikki T., additional, Peloso, Paul M., additional, Chen, Kun, additional, Li, Yihan, additional, Othman, Ahmed A., additional, Khatri, Amit, additional, Khan, Nasser S., additional, and Padley, Robert J., additional

Published
2018
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244. Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis

Author

Kjelgaard-Petersen, Cecilie F., primary, Platt, Adam, additional, Braddock, Martin, additional, Jenkins, Martin A., additional, Musa, Kishwar, additional, Graham, Emma, additional, Gantzel, Thorbjørn, additional, Slynn, Gillian, additional, Weinblatt, Michael E., additional, Karsdal, Morten A., additional, Thudium, Christian S., additional, and Bay-Jensen, Anne-C., additional

Published
2018
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245. Dual inhibition of tumour necrosis factor and interleukin-17A with ABT-122: open-label long-term extension studies in rheumatoid arthritis or psoriatic arthritis

Author

Genovese, Mark C, primary, Weinblatt, Michael E, additional, Mease, Philip J, additional, Aelion, Jacob A, additional, Peloso, Paul M, additional, Chen, Kun, additional, Li, Yihan, additional, Liu, John, additional, Othman, Ahmed A, additional, Khatri, Amit, additional, Mansikka, Heikki T, additional, and Leszczyński, Piotr, additional

Published
2018
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246. Development of a Molecular Signature to Monitor Pharmacodynamic Responses Mediated by In Vivo Administration of Glucocorticoids

Author

Hu, Yanhua, primary, Carman, Julie A., additional, Holloway, Deborah, additional, Kansal, Selena, additional, Fan, Li, additional, Goldstine, Christine, additional, Lee, Deborah, additional, Somerville, John E., additional, Latek, Robert, additional, Townsend, Robert, additional, Johnsen, Alyssa, additional, Connolly, Sean, additional, Bandyopadhyay, Somnath, additional, Shadick, Nancy, additional, Weinblatt, Michael E., additional, Furie, Richard, additional, and Nadler, Steven G., additional

Published
2018
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250. Oral Abstracts 7: RA Clinical * O37. 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, and Preeti, Shah

Subjects
medicine.medical_specialty, Rheumatology, business.industry, Radiography, medicine, Pharmacology (medical), Inflammation, In patient, Radiology, medicine.symptom, Axial spondyloarthritis, business, Joint (geology)
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 (

Published
2013

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