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201. Early clinical markers of aggressive multiple sclerosis

Author

Malpas, Charles B, primary, Manouchehrinia, Ali, additional, Sharmin, Sifat, additional, Roos, Izanne, additional, Horakova, Dana, additional, Havrdova, Eva Kubala, additional, Trojano, Maria, additional, Izquierdo, Guillermo, additional, Eichau, Sara, additional, Bergamaschi, Roberto, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Lugaresi, Alessandra, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Grammond, Pierre, additional, Grand’Maison, Francois, additional, Ozakbas, Serkan, additional, Van Pesch, Vincent, additional, Granella, Franco, additional, Hupperts, Raymond, additional, Pucci, Eugenio, additional, Boz, Cavit, additional, Iuliano, Gerardo, additional, Sidhom, Youssef, additional, Gouider, Riadh, additional, Spitaleri, Daniele, additional, Butzkueven, Helmut, additional, Soysal, Aysun, additional, Petersen, Thor, additional, Verheul, Freek, additional, Karabudak, Rana, additional, Turkoglu, Recai, additional, Ramo-Tello, Cristina, additional, Terzi, Murat, additional, Cristiano, Edgardo, additional, Slee, Mark, additional, McCombe, Pamela, additional, Macdonell, Richard, additional, Fragoso, Yara, additional, Olascoaga, Javier, additional, Altintas, Ayse, additional, Olsson, Tomas, additional, Hillert, Jan, additional, and Kalincik, Tomas, additional

Published
2019
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202. 134 Cladribine: a multicentre long-term efficacy biomarker australian study (CLOBAS)

Author

Lechner-Scott, Jeannette, primary, Maltby, Vicky, additional, Lyndon, Amanda, additional, Monif, Mastura, additional, Kilpatrick, Trevor, additional, Butzkueven, Helmut, additional, Taylor, Bruce, additional, McCombe, Pamela, additional, Hodgkinson, Suzanne, additional, Fabis-Pedrini, Marzena, additional, Kermode, Allan, additional, Barnett, Michael, additional, and Kalincik, Tomas, additional

Published
2019
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205. 002 Therapeutic lag in relapsing multiple sclerosis

Author

Roos, Izanne, primary, Frascoli, Federico, additional, Lechner-Scott, Jeannette, additional, McCombe, Pamela, additional, Macdonell, Richard, additional, Butzkueven, Helmut, additional, Malpas, Charles, additional, and Kalincik, Tomas, additional

Published
2019
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208. Gut microbiota in ALS: possible role in pathogenesis?

Author

McCombe, Pamela A., primary, Henderson, Robert D., additional, Lee, Aven, additional, Lee, John D., additional, Woodruff, Trent M., additional, Restuadi, Restuadi, additional, McRae, Allan, additional, Wray, Naomi R., additional, Ngo, Shyuan, additional, and Steyn, Frederik J., additional

Published
2019
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210. Missense mutations in the MLKL ‘brace’ region lead to lethal neonatal inflammation in mice and are present in high frequency in humans

Author

Hildebrand, Joanne M., primary, Kauppi, Maria, additional, Majewski, Ian J., additional, Liu, Zikou, additional, Cox, Allison, additional, Miyake, Sanae, additional, Petrie, Emma J., additional, Silk, Michael A., additional, Li, Zhixiu, additional, Tanzer, Maria C., additional, Young, Samuel N., additional, Hall, Cathrine, additional, Garnish, Sarah E., additional, Corbin, Jason, additional, Stutz, Michael D., additional, Gangatirkar, Pradnya, additional, Josefsson, Emma C., additional, Rigbye, Kristin, additional, Anderton, Holly, additional, Rickard, James A., additional, Tripaydonis, Anne, additional, Sheridan, Julie, additional, Scerri, Thomas S., additional, Czabotar, Peter A., additional, Zhang, Jian-Guo, additional, Allison, Cody C., additional, Pellegrini, Marc, additional, Tannahill, Gillian M., additional, Hatchell, Esme C., additional, Willson, Tracy A., additional, Stockwell, Dina, additional, de Graaf, Carolyn A., additional, Collinge, Janelle, additional, Hilton, Adrienne, additional, Silke, Natasha, additional, Spall, Sukhdeep K., additional, Chau, Diep, additional, Athanasopoulos, Vicki, additional, Metcalf, Donald, additional, Laxer, Ronald M., additional, Bassuk, Alexander G., additional, Darbro, Benjamin W., additional, Fiatarone Singh, Maria A., additional, Vlahovich, Nicole, additional, Hughes, David, additional, Kozlovskaia, Maria, additional, Ascher, David B., additional, Warnatz, Klaus, additional, Venhoff, Nils, additional, Thiel, Jens, additional, Blum, Stefan, additional, Reveille, John, additional, Hildebrand, Michael S., additional, Vinuesa, Carola G., additional, McCombe, Pamela, additional, Brown, Matthew A., additional, Kile, Ben T., additional, McLean, Catriona, additional, Bahlo, Melanie, additional, Masters, Seth L., additional, Nakano, Hiroyasu, additional, Ferguson, Polly J., additional, Murphy, James M., additional, Alexander, Warren S., additional, and Silke, John, additional

Published
2019
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211. Improved Clinical and MRI Disease Activity Outcomes, Including Slowing of Brain Volume Loss, in Alemtuzumab-Treated RRMS Patients: 8-Year Follow-up of CARE-MS I (TOPAZ Study) (P3.2-037)

Author

Pelletier, Daniel, primary, Arnold, Douglas L., additional, Boyko, Alexey N., additional, Comi, Giancarlo, additional, Hartung, Hans-Peter, additional, Havrdova, Eva Kubala, additional, Inshasi, Jihad Said, additional, McCombe, Pamela, additional, Nakamura, Kunio, additional, Oreja-Guevara, Celia, additional, Pozzilli, Carlo, additional, Selmaj, Krzysztof W., additional, Scott, Thomas F., additional, Chung, Luke, additional, Daizadeh, Nadia, additional, Afsar, Salman, additional, and Van Wijmeersch, Bart, additional

Published
2019
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212. Clinical determinants and therapeutic modifiers of relapse and disability outcomes in neuromyelitis optica spectrum disorder (P1.2-072)

Author

Kunchok, Amy, primary, Malpas, Charles, additional, Nytrova, Petra, additional, Havrdova, Eva, additional, Alroughani, Raed, additional, Terzi, Murat, additional, Yamout, Bassem, additional, Hor, Jyh Yung, additional, Karabudak, Rana, additional, Boz, Cavit, additional, Ozakbas, Serkan, additional, Urtaza, Francisco Javier Olascoaga, additional, Simo, Magdolna, additional, Granella, Franco, additional, Patti, Francesco, additional, McCombe, Pamela, additional, Csepany, Tunde, additional, Singhal, Bhim, additional, Bergamaschi, Roberto, additional, Fragoso, Yara, additional, Al-Harbi, Talal, additional, Turkoglu, Recai, additional, Lechner-Scott, Jeannette, additional, Laureys, Guy, additional, Oreja-Guevara, Celia, additional, Pucci, Eugenio, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Altintas, Ayse, additional, Soysal, Aysun, additional, Vucic, Steve, additional, Grand-Maison, Francois, additional, Madueno, Sara Eichau, additional, Ayuso, Guillermo Izquierdo, additional, Lugaresi, Alessandra, additional, Onofrj, Marco, additional, Trojano, Maria, additional, Marriott, Mark, additional, Butzkueven, Helmut, additional, Kister, Ilya, additional, and Kalincik, Tomas, additional

Published
2019
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213. Investigating the Effect of Teriflunomide on Brain Volume Loss in the Phase 3 TOPIC Study (P3.2-046)

Author

Sprenger, Till, primary, Lebrun-Frenay, Christine, additional, Vermersch, Patrick, additional, Park, Min Su, additional, Chinchilla, Dennis, additional, McCombe, Pamela, additional, Lincoln, John, additional, Kappos, Ludwig, additional, Bergsland, Niels, additional, Dwyer, Michael, additional, Cavalier, Steven, additional, Roesch, Nora, additional, Somera-Molina, Kathleen, additional, Poole, Elizabeth, additional, and Zivadinov, Robert, additional

Published
2019
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215. Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis

Author

Kalincik, Tomas, primary, Kubala Havrdova, Eva, additional, Horakova, Dana, additional, Izquierdo, Guillermo, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Grammond, Pierre, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Ozakbas, Serkan, additional, Kappos, Ludwig, additional, Kuhle, Jens, additional, Terzi, Murat, additional, Lechner-Scott, Jeannette, additional, Boz, Cavit, additional, Grand'Maison, Francois, additional, Prevost, Julie, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Granella, Franco, additional, Trojano, Maria, additional, Bergamaschi, Roberto, additional, Pucci, Eugenio, additional, Turkoglu, Recai, additional, McCombe, Pamela A, additional, Pesch, Vincent Van, additional, Van Wijmeersch, Bart, additional, Solaro, Claudio, additional, Ramo-Tello, Cristina, additional, Slee, Mark, additional, Alroughani, Raed, additional, Yamout, Bassem, additional, Shaygannejad, Vahid, additional, Spitaleri, Daniele, additional, Sánchez-Menoyo, José Luis, additional, Ampapa, Radek, additional, Hodgkinson, Suzanne, additional, Karabudak, Rana, additional, Butler, Ernest, additional, Vucic, Steve, additional, Jokubaitis, Vilija, additional, Spelman, Tim, additional, and Butzkueven, Helmut, additional

Published
2019
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219. The effect of ageing on human lymphocyte subsets: comparison of males and females

Author

Henderson Robert D, O'Sullivan John D, Hull Renee, Greer Judith M, Yan Jun, Read Stephen J, and McCombe Pamela A

Subjects
Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract Background There is reported to be a decline in immune function and an alteration in the frequency of circulating lymphocytes with advancing age. There are also differences in ageing and lifespan between males and females. We performed this study to see if there were differences between males and females in the frequency of the different lymphocyte subsets with age. Results Using flow cytometry we have examined different populations of peripheral blood leukocytes purified from healthy subjects with age ranging from the third to the tenth decade. We used linear regression analysis to determine if there is a linear relationship between age and cell frequencies. For the whole group, we find that with age there is a significant decline in the percentage of naïve T cells and CD8+ T cells, and an increase in the percentage of effector memory cells, CD4+foxp3+ T cells and NK cells. For all cells where there was an effect of ageing, the slope of the curve was greater for men than for women and this was statistically significant for CD8+αβ+ T cells and CD3+CD45RA-CCR7- effector memory cells. There was also a difference for naïve cells but this was not significant. Conclusion The cause of the change in percentage of lymphocyte subsets with age, and the different effects on males and females is not fully understood but warrants further study.

Published
2010
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221. Real-world effectiveness of cladribine for Australian patients with multiple sclerosis: An MSBase registry substudy.

Author

Lizak, Nathaniel, Hodgkinson, Suzanne, Butler, Ernest, Lechner-Scott, Jeannette, Slee, Mark, McCombe, Pamela Ann, Shaw, Cameron, Skibina, Olga, Vucic, Steve, Shuey, Neil, Barnett, Michael H, Parratt, John, Butzkueven, Helmut, Jack, Dominic, Fabris, Jessica, and Kalincik, Tomas

Subjects
MULTIPLE sclerosis, MEDICAL registry personnel, OLDER patients, DISEASE relapse, AGE of onset, CLINICAL trials
Abstract

Background/objective: Observational clinical data from cladribine-treated patients with relapsing forms of multiple sclerosis (MS) were recorded in the Australian MS registry powered by the MSBase registry platform (5-year follow-up) and analysed to complement information from the pivotal cladribine clinical trials in MS. Methods: A cohort of 90 cladribine-treated patients with follow-up data reported by treating physicians and recorded in the Australian MSBase registry (database lock February 2016) were examined. Clinical data included Expanded Disability Status Scale (EDSS) scores, relapses and other disease-modifying drugs (DMDs) administered before and after cladribine treatment. Results: Mean age on starting cladribine was 47 years; mean age at MS onset was 34 years, and median baseline EDSS score was 5.25. Disability trajectories in patients with sufficient follow-up suggested an overall increasing trend prior to cladribine treatment which was reduced during the 2-year post-treatment. Approximately 80% of patients were EDSS progression-free, 65% remained relapse-free after 2 years and median time to next DMD was 1.7 years. Conclusion: These observational data suggest a disease-modifying effect in this cohort of relapsing MS patients characterised by older and more disabled patients. Since these data represent a single-arm cohort, clinical trials and larger comparative post-marketing studies are needed to validate and extend these findings. [ABSTRACT FROM AUTHOR]

Published
2021
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222. Clinical and electrophysiological examination of pinch strength in patients with amyotrophic lateral sclerosis.

Author

Lee, John D., Heshmat, Saman, Heggie, Susan, Thorpe, Kathryn A., McCombe, Pamela A., and Henderson, Robert D.

Abstract

Background: The split‐hand concept has highlighted the preferential wasting of the thenar side of the hand in amyotrophic lateral sclerosis (ALS). Our objective is to re‐explore pinch grip strength to assess whether it has the potential to be a practical biomarker of ALS. Methods: We measured different pinch grip strengths (thumb, index, and fifth) using a pinch gauge from both hands of 54 ALS patients and correlated this with the Medical Research Council (MRC) score, the upper‐limb component of the revised ALS Functional Rating Scale – Revised (ALSFRS‐R) score, and compound muscle action potentials (CMAPs) that comprise the split‐hand index. Results: Pinch grip strength using any of the three fingers showed a positive correlation with its corresponding CMAP, MRC grading, and upper‐limb ALSFRS‐R score. The thumb pinch showed the strongest correlation with the split‐hand index and MRC grading. Conclusions: Pinch grip strength test using a simple gauge deserves further study as a potentially practical biomarker of ALS. [ABSTRACT FROM AUTHOR]

Published
2021
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223. Exploring targets and therapies for amyotrophic lateral sclerosis: current insights into dietary interventions

Author

Ngo,Shyuan, Mi,Jia D, Henderson,Robert, McCombe,Pamela A, and Steyn,Frederik

Subjects
Degenerative Neurological and Neuromuscular Disease
Abstract

Shyuan T Ngo,1–5 Jia D Mi,1 Robert D Henderson,3,4 Pamela A McCombe,3,4 Frederik J Steyn3–5 1School of Biomedical Sciences, 2Queensland Brain Institute, 3Centre for Clinical Research, The University of Queensland, 4Department of Neurology, Royal Brisbane & Women’s Hospital, 5Wesley Medical Research, The Wesley Hospital, Auchenflower, Brisbane, QLD, Australia Abstract: A growing number of preclinical and human studies demonstrate a disease-modifying effect of nutritional state in amyotrophic lateral sclerosis (ALS). The management of optimal nutrition in ALS is complicated, as physiological, physical, and psychological effects of the disease need to be considered and addressed accordingly. In this regard, multidisciplinary care teams play an integral role in providing dietary guidance to ALS patients and their carers. However, with an increasing research focus on the use of dietary intervention strategies to manage disease symptoms and improve prognosis in ALS, many ALS patients are now seeking or are actively engaged in using complementary and alternative therapies that are dietary in nature. In this article, we review the aspects of appetite control, energy balance, and the physiological effects of ALS relative to their impact on overall nutrition. We then provide current insights into dietary interventions for ALS, considering the mechanisms of action of some of the ­common dietary interventions used in ALS, discussing their validity in the context of clinical trials. Keywords: ALS, treatment, alternative off-label therapies, antioxidants, clinical trials, nutrition

Published
2017

224. Natalizumab, Fingolimod, and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

Author

Yeh, Wei Zhen, Widyastuti, Putu Ayu, Van der Walt, Anneke, Stankovich, Jim, Havrdova, Eva, Horakova, Dana, Vodehnalova, Karolina, Ozakbas, Serkan, Eichau, Sara, Duquette, Pierre, Kalincik, Tomas, Patti, Francesco, Boz, Cavit, Terzi, Murat, Yamout, Bassem I., Lechner-Scott, Jeannette, Sola, Patrizia, Skibina, Olga G., Barnett, Michael, Onofrj, Marco, Sá, Maria José, McCombe, Pamela Ann, Grammond, Pierre, Ampapa, Radek, Grand'Maison, Francois, Bergamaschi, Roberto, Spitaleri, Daniele L.A., Van Pesch, Vincent, Cartechini, Elisabetta, Hodgkinson, Suzanne, Soysal, Aysun, Saiz, Albert, Gresle, Melissa, Uher, Tomas, Maimone, Davide, Turkoglu, Recai, Hupperts, Raymond M.M., Amato, Maria Pia, Granella, Franco, Oreja-Guevara, Celia, Altintas, Ayse, Macdonell, Richard A., Castillo-Trivino, Tamara, Butzkueven, Helmut, Alroughani, Raed, and Jokubaitis, Vilija G.

Published
2021
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225. Patient with ALS with a novel TBK1 mutation, widespread brain involvement, behaviour changes and metabolic dysfunction

Author

McCombe, Pamela A, primary, Ngo, Shyuan T, additional, Guo, Christine Cong, additional, Fazlollahi, Amir, additional, Bollmann, Saskia, additional, Wang, Liting, additional, Hu, Xintao, additional, Barth, Markus, additional, Salvado, Olivier, additional, Davis, Mark, additional, Ceslis, Amelia, additional, Robinson, Gail, additional, Henderson, Robert D, additional, and Steyn, Frederik J, additional

Published
2018
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227. Hypermetabolism in ALS is associated with greater functional decline and shorter survival

Author

Steyn, Frederik J, primary, Ioannides, Zara A, additional, van Eijk, Ruben P A, additional, Heggie, Susan, additional, Thorpe, Kathryn A, additional, Ceslis, Amelia, additional, Heshmat, Saman, additional, Henders, Anjali K, additional, Wray, Naomi R, additional, van den Berg, Leonard H, additional, Henderson, Robert D, additional, McCombe, Pamela A, additional, and Ngo, Shyuan T, additional

Published
2018
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228. Durable Efficacy and Safety With Alemtuzumab in CARE-MS I Patients Switching From SC IFNB-1a: 5-Year Follow-up (TOPAZ Study) (P6.366)

Author

Steingo, Brian, primary, Oreja-Guevara, Celia, additional, Alroughani, Raed, additional, Brassat, David, additional, Boyko, Alexey N., additional, McCombe, Pamela, additional, Van Wijmeersch, Bart, additional, Margolin, David H., additional, Melanson, Maria, additional, Daizadeh, Nadia, additional, Rodriguez, Claudio E., additional, and Vermersch, Patrick, additional

Published
2018
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229. Presentation of Neuromyelitis Optica (NMO) in patients from different racial groups: analysis of the global NMOBase Registry (P6.407)

Author

Kister, Ilya, primary, Bacon, Tamar, additional, Shaygannejad, Vahid, additional, Havrdova, Eva, additional, Alroughani, Raed, additional, Terzi, Murat, additional, Altintas, Ayse, additional, Hor, Jyh Yung, additional, Al-Harbi, Talal, additional, Boz, Cavit, additional, Bergamaschi, Roberto, additional, Ozakbas, Serkan, additional, Ferraro, Diana, additional, Fragoso, Yara, additional, Laureys, Guy, additional, Soysal, Aysun, additional, Majdinassab, Nastaran, additional, Onofrj, Marco, additional, Pucci, Eugenio, additional, Vucic, Ostoja (Steve), additional, Slee, Mark, additional, Lechner-Scott, Jeannette, additional, Rojas, Juan Ignacio, additional, Burgos, Marcos, additional, Triviño, Tamara Castillo, additional, Reid, Allyson, additional, Rimler, Zoe, additional, McCombe, Pamela, additional, Granella, Franco, additional, Polyzou-Konsta, Maria-Anna, additional, Dreyer, Michael, additional, Iuliano, Gerardo, additional, Kermode, Allan, additional, Shaw, Cameron, additional, Weinstock-Guttman, Bianca, additional, and Butzkueven, Helmut, additional

Published
2018
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230. Durable Clinical Efficacy of Alemtuzumab in Patients With Active RRMS in the Absence of Continuous Treatment: 7-Year Follow-up of CARE-MS I Patients (TOPAZ Study) (P6.376)

Author

Vermersch, Patrick, primary, Coles, Alasdair J., additional, Boyko, Alexey N., additional, De Seze, Jérôme, additional, Hartung, Hans-Peter, additional, Havrdova, Eva, additional, Inshasi, Jihad Said, additional, McCombe, Pamela, additional, Montalban, Xavier, additional, Pozzilli, Carlo, additional, Selmaj, Krzysztof W., additional, Margolin, David H., additional, Melanson, Maria, additional, Daizadeh, Nadia, additional, Rodriguez, Claudio E., additional, and Van Wijmeersch, Bart, additional

Published
2018
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232. Predictors of long-term disability accrual in relapse-onset multiple sclerosis

Author

Jokubaitis, Vilija G, Spelman, Tim, Kalincik, Tomas, Lorscheider, Johannes, Havrdova, Eva, Horakova, Dana, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Izquierdo, Guillermo, Grammond, Pierre, Van Pesch, Vincent, Pucci, Eugenio, Grand'Maison, François, Hupperts, Raymond, Granella, Franco, Sola, Patrizia, Bergamaschi, Roberto, Iuliano, Gerardo, Spitaleri, Daniele, Boz, Cavit, Hodgkinson, Suzanne, Olascoaga, Javier, Verheul, Freek, McCombe, Pamela, Petersen, Thor, Rozsa, Csilla, Lechner-Scott, Jeannette, Saladino, Maria Laura, Farina, Deborah, Iaffaldano, Pietro, Paolicelli, Damiano, Butzkueven, Helmut, Lugaresi, Alessandra, Trojano, Maria, and MSBase Study Group

Subjects
Adult, Male, Multiple Sclerosis, Glatiramer Acetate, Interferon-beta, Protective Factors, Prognosis, Disability Evaluation, Young Adult, Pregnancy, Recurrence, Risk Factors, Humans, Female, Registries, Follow-Up Studies
Abstract

To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis. Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed. We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0-2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10(-22) ). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = -0.86, p = 1.3 × 10(-9) ). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = -0.36, p = 0.009). We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89-100.

Published
2016

233. Predictors of long-term disability accrual in relapse-onset multiple sclerosis

Author

Jokubaitis, Vilija G., Spelman, Tim, Kalincik, Tomas, Lorscheider, Johannes, Havrdova, Eva, Horakova, Dana, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Izquierdo, Guillermo, Grammond, Pierre, Van Pesch, Vincent, Pucci, Eugenio, Grand'Maison, Francois, Hupperts, Raymond, Granella, Franco, Sola, Patrizia, Bergamaschi, Roberto, Iuliano, Gerardo, Spitaleri, Daniele, Boz, Cavit, Hodgkinson, Suzanne, Olascoaga, Javier, Verheul, Freek, McCombe, Pamela, Petersen, Thor, Rozsa, Csilla, Lechner-Scott, Jeannette, Laura Saladino, Maria, Farina, Deborah, Iaffaldano, Pietro, Paolicelli, Damiano, Butzkueven, Helmut, Lugaresi, Alessandra, Trojano, Maria, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), and Klinische Neurowetenschappen

Subjects
Adult, Male, Multiple Sclerosis, Glatiramer Acetate, Interferon-beta, Protective Factors, Prognosis, Disability Evaluation, Young Adult, Pregnancy, Recurrence, Risk Factors, Journal Article, Humans, Female, Registries, Follow-Up Studies
Abstract

OBJECTIVE: To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis.METHODS: Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed.RESULTS: We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0-2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10(-22) ). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = -0.86, p = 1.3 × 10(-9) ). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = -0.36, p = 0.009).INTERPRETATION: We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89-100.

Published
2015

234. THUR 196 Pregnancy outcomes in alemtuzumab-treated rrms patients

Author

Chung Luke, Compston D Alastair S, McCombe Pamela, Chambers Christina, Rog David, Oh Jiwon, Hellwig Kerstin, and Daizadeh Nadia

Subjects
musculoskeletal diseases, medicine.medical_specialty, Pregnancy, education.field_of_study, business.industry, Obstetrics, Incidence (epidemiology), Population, medicine.disease, Psychiatry and Mental health, Female patient, Medicine, Alemtuzumab, Surgery, Observational study, Neurology (clinical), Dosing, business, Pregnancy outcomes, education, human activities, medicine.drug
Abstract

Murine studies show no alemtuzumab-related teratogenicity, but no controlled human clinical studies of alemtuzumab in pregnancy exist. In phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, patients received 2 annual alemtuzumab courses. Two extension studies provided longer-term evaluation (NCT00930553; TOPAZ [NCT02255656]). Pregnant/lactating patients were ineligible for further treatment but were followed up for safety. As of 1 April 2017, 248 pregnancies occurred in 156/972 alemtuzumab-treated female patients (mean [SD] age at conception, 32.5 [4.4] years; mean [SD] time from last alemtuzumab dose to conception, 33.5 [22.6] months; 16 within 4 months of dosing), with 218 completed, 14 ongoing, and 16 with unknown outcomes. Of completed pregnancies with known outcomes, 147 (67%) were live births with no congenital abnormalities or birth defects. There were 48 (22%) spontaneous abortions, 22 (10%) elective abortions, and 1 (0.5%) stillbirth. To date, there has been no signal for teratogenicity. Incidence of spontaneous abortions was comparable with treatment-naive MS patients (5%–21%) and the general population (17%–22%). Real-world data are currently collected by the International Lemtrada Pregnancy Exposure Registry, a prospective, non-interventional, observational safety study enrolling patients in ≥19 countries who become pregnant within 4 months of alemtuzumab exposure.Study Support: Sanofi.

Published
2018

235. Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis

Author

Benyamin, Beben, primary, He, Ji, additional, Zhao, Qiongyi, additional, Gratten, Jacob, additional, Garton, Fleur, additional, Leo, Paul J., additional, Liu, Zhijun, additional, Mangelsdorf, Marie, additional, Al-Chalabi, Ammar, additional, Anderson, Lisa, additional, Butler, Timothy J., additional, Chen, Lu, additional, Chen, Xiang-Ding, additional, Cremin, Katie, additional, Deng, Hong-Weng, additional, Devine, Matthew, additional, Edson, Janette, additional, Fifita, Jennifer A., additional, Furlong, Sarah, additional, Han, Ying-Ying, additional, Harris, Jessica, additional, Henders, Anjali K., additional, Jeffree, Rosalind L., additional, Jin, Zi-Bing, additional, Li, Zhongshan, additional, Li, Ting, additional, Li, Mengmeng, additional, Lin, Yong, additional, Liu, Xiaolu, additional, Marshall, Mhairi, additional, McCann, Emily P., additional, Mowry, Bryan J., additional, Ngo, Shyuan T., additional, Pamphlett, Roger, additional, Ran, Shu, additional, Reutens, David C., additional, Rowe, Dominic B., additional, Sachdev, Perminder, additional, Shah, Sonia, additional, Song, Sharon, additional, Tan, Li-Jun, additional, Tang, Lu, additional, van den Berg, Leonard H., additional, van Rheenen, Wouter, additional, Veldink, Jan H., additional, Wallace, Robyn H., additional, Wheeler, Lawrie, additional, Williams, Kelly L., additional, Wu, Jinyu, additional, Wu, Xin, additional, Yang, Jian, additional, Yue, Weihua, additional, Zhang, Zong-Hong, additional, Zhang, Dai, additional, Noakes, Peter G., additional, Blair, Ian P., additional, Henderson, Robert D., additional, McCombe, Pamela A., additional, Visscher, Peter M., additional, Xu, Huji, additional, Bartlett, Perry F., additional, Brown, Matthew A., additional, Wray, Naomi R., additional, and Fan, Dongsheng, additional

Published
2017
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236. Whole exome sequencing and DNA methylation analysis in a clinical amyotrophic lateral sclerosis cohort

Author

Garton, Fleur C., primary, Benyamin, Beben, additional, Zhao, Qiongyi, additional, Liu, Zhijun, additional, Gratten, Jacob, additional, Henders, Anjali K., additional, Zhang, Zong-Hong, additional, Edson, Janette, additional, Furlong, Sarah, additional, Morgan, Sarah, additional, Heggie, Susan, additional, Thorpe, Kathryn, additional, Pfluger, Casey, additional, Mather, Karen A., additional, Sachdev, Perminder S., additional, McRae, Allan F., additional, Robinson, Matthew R., additional, Shah, Sonia, additional, Visscher, Peter M., additional, Mangelsdorf, Marie, additional, Henderson, Robert D., additional, Wray, Naomi R., additional, and McCombe, Pamela A., additional

Published
2017
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237. Incidence and prevalence of NMOSD in Australia and New Zealand

Author

Bukhari, Wajih, primary, Prain, Kerri M, additional, Waters, Patrick, additional, Woodhall, Mark, additional, O‘Gorman, Cullen M, additional, Clarke, Laura, additional, Silvestrini, Roger A, additional, Bundell, Christine S, additional, Abernethy, David, additional, Bhuta, Sandeep, additional, Blum, Stefan, additional, Boggild, Mike, additional, Boundy, Karyn, additional, Brew, Bruce J, additional, Brown, Matthew, additional, Brownlee, Wallace J, additional, Butzkueven, Helmut, additional, Carroll, William M, additional, Chen, Celia, additional, Coulthard, Alan, additional, Dale, Russell C, additional, Das, Chandi, additional, Dear, Keith, additional, Fabis-Pedrini, Marzena J, additional, Fulcher, David, additional, Gillis, David, additional, Hawke, Simon, additional, Heard, Robert, additional, Henderson, Andrew P D, additional, Heshmat, Saman, additional, Hodgkinson, Suzanne, additional, Jimenez-Sanchez, Sofia, additional, Killpatrick, Trevor, additional, King, John, additional, Kneebone, Christopher, additional, Kornberg, Andrew J, additional, Lechner-Scott, Jeannette, additional, Lin, Ming-Wei, additional, Lynch, Christpher, additional, Macdonell, Richard, additional, Mason, Deborah F, additional, McCombe, Pamela A, additional, Pender, Michael P, additional, Pereira, Jennifer A, additional, Pollard, John D, additional, Reddel, Stephen W, additional, Shaw, Cameron, additional, Spies, Judith, additional, Stankovich, James, additional, Sutton, Ian, additional, Vucic, Steve, additional, Walsh, Michael, additional, Wong, Richard C, additional, Yiu, Eppie M, additional, Barnett, Michael H, additional, Kermode, Allan G, additional, Marriott, Mark P, additional, Parratt, John D E, additional, Slee, Mark, additional, Taylor, Bruce V, additional, Willoughby, Ernest, additional, Wilson, Robert J, additional, Vincent, Angela, additional, and Broadley, Simon A, additional

Published
2017
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239. timing of high-efficacy disease modifying therapies for relapsing-remitting multiple sclerosis

Author

Merkel, Bernd, primary, Jokubaitis, Vilija, additional, Spelman, Tim, additional, Lechner-Scott, Jeannette, additional, McCombe, Pamela, additional, Slee, Mark, additional, Vucic, Steve, additional, Skibina, Olga, additional, Barnett, Michael, additional, Hodgkinson, Suzanne, additional, Butzkueven, Helmut, additional, and Kalincik, Tomas, additional

Published
2017
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246. Durable Improvement in Clinical Outcomes in Patients With Relapsing-Remitting Multiple Sclerosis Who Discontinued SC IFNB-1a and Initiated Alemtuzumab: CARE-MS I Extension Study 4-Year Follow-up (P5.360)

Author

Oreja-Guevara, Celia, primary, Alroughani, Raed, additional, Brassat, David, additional, Boyko, Alexey N, additional, McCombe, Pamela, additional, Steingo, Brian, additional, Van Wijmeersch, Bart, additional, Margolin, David H, additional, Thangavelu, Karthinathan, additional, Rodriguez, Claudio E, additional, and Vermersch, Patrick, additional

Published
2017
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248. Improvements in Clinical Outcomes With Alemtuzumab in Treatment-Naive Patients With Active Relapsing-Remitting Multiple Sclerosis Are Durable Over 6 Years in the Absence of Continuous Treatment (CARE-MS I) (S24.005)

Author

Singer, Barry, primary, Coles, Alasdair J, additional, Boyko, Alexey N, additional, Cohen, Jeffrey A, additional, De Seze, Jérôme, additional, Fox, Edward J, additional, Havrdova, Eva, additional, Hartung, Hans-Peter, additional, Inshasi, Jihad Said, additional, McCombe, Pamela, additional, Selmaj, Krzysztof W, additional, Vermersch, Patrick, additional, Van Wijmeersch, Bart, additional, Margolin, David H, additional, Thangavelu, Karthinathan, additional, Rodriguez, Claudio, additional, and Montalban, Xavier, additional

Published
2017
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249. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study

Author

Kalincik, Tomas, primary, Brown, J William L, additional, Robertson, Neil, additional, Willis, Mark, additional, Scolding, Neil, additional, Rice, Claire M, additional, Wilkins, Alastair, additional, Pearson, Owen, additional, Ziemssen, Tjalf, additional, Hutchinson, Michael, additional, McGuigan, Christopher, additional, Jokubaitis, Vilija, additional, Spelman, Tim, additional, Horakova, Dana, additional, Havrdova, Eva, additional, Trojano, Maria, additional, Izquierdo, Guillermo, additional, Lugaresi, Alessandra, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Grammond, Pierre, additional, Alroughani, Raed, additional, Pucci, Eugenio, additional, Sola, Patrizia, additional, Hupperts, Raymond, additional, Lechner-Scott, Jeannette, additional, Terzi, Murat, additional, Van Pesch, Vincent, additional, Rozsa, Csilla, additional, Grand'Maison, François, additional, Boz, Cavit, additional, Granella, Franco, additional, Slee, Mark, additional, Spitaleri, Daniele, additional, Olascoaga, Javier, additional, Bergamaschi, Roberto, additional, Verheul, Freek, additional, Vucic, Steve, additional, McCombe, Pamela, additional, Hodgkinson, Suzanne, additional, Sanchez-Menoyo, Jose Luis, additional, Ampapa, Radek, additional, Simo, Magdolna, additional, Csepany, Tunde, additional, Ramo, Cristina, additional, Cristiano, Edgardo, additional, Barnett, Michael, additional, Butzkueven, Helmut, additional, and Coles, Alasdair, additional

Published
2017
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250. Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis

Author

Tao, Chunrong, primary, Simpson, Steve, additional, van der Mei, Ingrid, additional, Blizzard, Leigh, additional, Havrdova, Eva, additional, Horakova, Dana, additional, Shaygannejad, Vahid, additional, Lugaresi, Alessandra, additional, Izquierdo, Guillermo, additional, Trojano, Maria, additional, Duquette, Pierre, additional, Girard, Marc, additional, Grand'Maison, Franois, additional, Grammond, Pierre, additional, Alroughani, Raed, additional, Terzi, Murat, additional, Oreja-Guevara, Celia, additional, Sajedi, Seyed Aidin, additional, Iuliano, Gerardo, additional, Sola, Patrizia, additional, Lechner-Scott, Jeannette, additional, Pesch, Vincent Van, additional, Pucci, Eugenio, additional, Bergamaschi, Roberto, additional, Barnett, Michael, additional, Ramo, Cristina, additional, Singhal, Bhim, additional, LA Spitaleri, Daniele, additional, Slee, Mark, additional, Verheul, Freek, additional, Fernández Bolaños, Ricardo, additional, Amato, Maria Pia, additional, Cristiano, Edgardo, additional, Granella, Franco, additional, Hodgkinson, Suzanne, additional, Fiol, Marcela, additional, Gray, Orla, additional, McCombe, Pamela, additional, Saladino, Maria Laura, additional, Sánchez Menoyo, José Luis, additional, Shuey, Neil, additional, Vucic, Steve, additional, Shaw, Cameron, additional, Deri, Norma, additional, Arruda, Walter Oleschko, additional, Butzkueven, Helmut, additional, Spelman, Tim, additional, and Taylor, Bruce V, additional

Published
2016
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