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Ramanujam, Ryan
Publications (9 of 9) Show all publications
Jensen, P. E., Ramanujam, R. & Sorensen, P. S. (2019). Detection and kinetics of persistent neutralizing anti-interferon-beta antibodies in patients with multiple sclerosis. Results from the ABIRISK prospective cohort study. Journal of Neuroimmunology, 326, 19-27
Open this publication in new window or tab >>Detection and kinetics of persistent neutralizing anti-interferon-beta antibodies in patients with multiple sclerosis. Results from the ABIRISK prospective cohort study
2019 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 326, p. 19-27Article in journal (Refereed) Published
Abstract [en]

Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-beta) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-beta-specific rabbit polyclonal and human monoclonal antibodies were tested, the bioassay was the more sensitive to detect IFN-beta ADA in patients' sera. For clinical samples, selection of method of ELISA should be evaluated prior to the use of a multi-tiered approach. A titer threshold value is reported that may be used as a predictor for persistently positive neutralizing ADA.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Multiple sclerosis, Interferon-beta, Luciferase-based bioassay, Bridging ELISA, Anti-drug antibodies, Neutralizing antibodies
National Category
Neurosciences
Identifiers
urn:nbn:se:kth:diva-242973 (URN)10.1016/j.jneuroim.2018.11.002 (DOI)000455693200004 ()30447419 (PubMedID)2-s2.0-85056449193 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme
Note

QC 20190207

Available from: 2019-02-07 Created: 2019-02-07 Last updated: 2019-02-07Bibliographically approved
Manouchehrinia, A., Hedstrom, A. K., Alfredsson, L., Olsson, T., Hillert, J. & Ramanujam, R. (2018). Association of Pre-Disease Body Mass Index With Multiple Sclerosis Prognosis. Frontiers in Neurology, 9, Article ID 232.
Open this publication in new window or tab >>Association of Pre-Disease Body Mass Index With Multiple Sclerosis Prognosis
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2018 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 232Article in journal (Refereed) Published
Abstract [en]

Both high body mass index (BMI) and smoking tobacco are known risk factors for developing multiple sclerosis (MS). However, it is unclear whether BMI, like smoking, is a risk factor for the secondary progressive (SP) course. We, therefore, sought to determine if high/low BMI at age 20 is associated to risk of SP development, in the context of smoking status. Using data from MS patients with BMI and smoking information available, we examined relapsing onset patients with MS onset after 20 years of age. Cox regressions were conducted on smokers and non-smokers, with BMI as the main exposure. In total, 5,598 relapsing onset MS patients were included. The models demonstrated that BMI > 30 was associated to increased risk of SPMS in smokers (hazard ratio 1.50, p = 0.036). This association of obesity at age 20 with increased risk of SP was not observed in non-smokers (hazard rate 0.97, p = 0.900). Since the risk is confined to smokers, the interaction observed may give insight to disease driving mechanisms.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2018
Keywords
body mass index, progression, disability, secondary progressive MS, multiple sclerosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:kth:diva-228424 (URN)10.3389/fneur.2018.00232 (DOI)000431882000001 ()2-s2.0-85047018462 (Scopus ID)
Note

QC 20180529

Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-05-29Bibliographically approved
Manouchehrinia, A., Chachólski, W., Hillert, J. & Ramanujam, R. (2018). Topological data analysis to identify subgroups of multiple sclerosis patients with faster disease progression. Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 342-343
Open this publication in new window or tab >>Topological data analysis to identify subgroups of multiple sclerosis patients with faster disease progression
2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 342-343Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurosciences
Identifiers
urn:nbn:se:kth:diva-239108 (URN)000446861401025 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Note

QC 20181121

Available from: 2018-11-21 Created: 2018-11-21 Last updated: 2018-11-21Bibliographically approved
Link, J., Ramanujam, R., Auer, M., Ryner, M., Hassler, S., Bachelet, D., . . . Fogdell-Hahn, A. (2017). Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe: A descriptive study of test results. PLoS ONE, 12(2), Article ID e0170395.
Open this publication in new window or tab >>Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe: A descriptive study of test results
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 2, article id e0170395Article in journal (Refereed) Published
Abstract [en]

Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFN beta) and natalizumab have been pooled and characterized through collaboration within a European consortium. The aim of this study was to report on the clinical practice of ADA testing in Europe, considering the number of ADA tests performed and type of ADA assays used, and to determine the frequency of ADA testing against the different drug preparations in different countries. A common database platform (tranSMART) for querying, analyzing and storing retrospective data of MS cohorts was set up to harmonize the data and compare results of ADA tests between different countries. Retrospective data from six countries (Sweden, Austria, Spain, Switzerland, Germany and Denmark) on 20,695 patients and on 42,555 samples were loaded into tranSMART including data points of age, gender, treatment, samples, and ADA results. The previously observed immunogenic difference among the four IFN beta preparations was confirmed in this large dataset. Decreased usage of the more immunogenic preparations IFN beta-1a subcutaneous (s.c.) and IFN beta-1b s.c. in favor of the least immunogenic preparation IFN beta-1a intramuscular (i.m.) was observed. The median time from treatment start to first ADA test correlated with time to first positive test. Shorter times were observed for IFN beta-1b-Extavia s. c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFN beta-1a i. m. (1.41 and 2.27 years), IFN beta-1b-Betaferon s. c. (2.51 and 1.96 years) and IFN beta-1a s. c. (2.11 and 2.09 years) which were available years before routine testing began. A higher rate of anti-IFN beta ADA was observed in test samples taken from older patients. Testing for ADA varies between different European countries and is highly dependent on the policy within each country. For drugs where routine monitoring of ADA is not in place, there is a risk that some patients remain on treatment for several years despite ADA positivity. For drugs where a strategy of ADA testing is introduced with the release of the drug, there is a reduced risk of having ADA positive patients and thus of less efficient treatment. This indicates that potential savings in health cost might be achieved by routine analysis of ADA.

Place, publisher, year, edition, pages
Public Library of Science, 2017
National Category
Mathematics
Identifiers
urn:nbn:se:kth:diva-203829 (URN)10.1371/journal.pone.0170395 (DOI)000393705500005 ()28170401 (PubMedID)2-s2.0-85012009747 (Scopus ID)
Note

QC 20170321

Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2017-11-29Bibliographically approved
Kavaliunas, A., Manouchehrinia, A., Stawiarz, L., Ramanujam, R., Agholme, J., Hedstrom, A. K., . . . Hillert, J. (2017). Importance of early treatment initiation in the clinical course of multiple sclerosis. Multiple Sclerosis, 23(9), 1233-1240
Open this publication in new window or tab >>Importance of early treatment initiation in the clinical course of multiple sclerosis
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2017 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 9, p. 1233-1240Article in journal (Refereed) Published
Abstract [en]

Objectives: The aim of this study was to identify factors influencing the long-term clinical progression of multiple sclerosis (MS). A special objective was to investigate whether early treatment decisions influence outcome. Methods: We included 639 patients diagnosed with MS from 2001 to 2007. The median follow-up time was 99 months (8.25 years). Cox regression models were applied to identify factors correlating with the outcome variable defined as time from treatment start to irreversible score 4 of the Expanded Disability Status Scale (EDSS). Results: Patients initiated on treatment later had a greater risk of reaching EDSS 4 (hazard ratio of 1.074 (95% confidence interval (CI), 1.048-1.101)), increased by 7.4% for every year of delay in treatment start after MS onset. Patients who started treatment after 3 years from MS onset reached the outcome sooner with hazard ratio of 2.64 (95% CI, 1.71-4.08) compared with the patients who started treatment within 1 year from MS onset. Baseline EDSS and age at onset were found to be predictive factors of disability progression. Conclusion: Early treatment initiation was associated with a better clinical outcome. In addition, we confirmed the well-established prognostic factors of late age at onset and early disability.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2017
Keywords
Multiple sclerosis, drug therapy, treatment outcome, disease progression, disability evaluation, cohort studies, survival analysis
National Category
Neurology
Identifiers
urn:nbn:se:kth:diva-212338 (URN)10.1177/1352458516675039 (DOI)000406386600011 ()2-s2.0-85026672961 (Scopus ID)
Note

QC 20170823

Available from: 2017-08-23 Created: 2017-08-23 Last updated: 2017-08-23Bibliographically approved
Scolamiero, M., Chachólski, W., Lundman, A., Ramanujam, R. & Öberg, S. (2017). Multidimensional Persistence and Noise. Foundations of Computational Mathematics, 17(6), 1367-1406
Open this publication in new window or tab >>Multidimensional Persistence and Noise
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2017 (English)In: Foundations of Computational Mathematics, ISSN 1615-3375, E-ISSN 1615-3383, Vol. 17, no 6, p. 1367-1406Article in journal (Refereed) Published
Abstract [en]

In this paper, we study multidimensional persistence modules (Carlsson and Zomorodian in Discrete Comput Geom 42(1):71–93, 2009; Lesnick in Found Comput Math 15(3):613–650, 2015) via what we call tame functors and noise systems. A noise system leads to a pseudometric topology on the category of tame functors. We show how this pseudometric can be used to identify persistent features of compact multidimensional persistence modules. To count such features, we introduce the feature counting invariant and prove that assigning this invariant to compact tame functors is a 1-Lipschitz operation. For one-dimensional persistence, we explain how, by choosing an appropriate noise system, the feature counting invariant identifies the same persistent features as the classical barcode construction.

Place, publisher, year, edition, pages
Springer-Verlag New York, 2017
Keywords
Multidimensional persistence, Noise systems, Persistence modules, Stable invariants, Computational methods, Mathematical techniques, Functors, Persistent feature, Pseudo-metrices, Algebra
National Category
Algebra and Logic
Identifiers
urn:nbn:se:kth:diva-197199 (URN)10.1007/s10208-016-9323-y (DOI)000415739500001 ()2-s2.0-84976493395 (Scopus ID)
Note

QC 20161212

Available from: 2016-12-12 Created: 2016-11-30 Last updated: 2017-12-08Bibliographically approved
Kavaliunas, A., Manouchehrinia, A., Stawiarz, L., Ramanujam, R., Agholme, J., Hedstrom, A. K., . . . Hillert, J. (2016). Importance of early treatment initiation in the clinical course of multiple sclerosis. Paper presented at 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND. Multiple Sclerosis, 22, 642-642
Open this publication in new window or tab >>Importance of early treatment initiation in the clinical course of multiple sclerosis
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2016 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 642-642Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Sage Publications, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:kth:diva-204144 (URN)000383267202421 ()
Conference
32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND
Note

QC 20170327

Available from: 2017-03-27 Created: 2017-03-27 Last updated: 2017-11-29Bibliographically approved
Bachelet, D., Hassler, S., Mbogning, C., Link, J., Ryner, M., Ramanujam, R., . . . Broet, P. (2016). Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis. PLoS ONE, 11(11), Article ID e0162752.
Open this publication in new window or tab >>Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, article id e0162752Article in journal (Refereed) Published
Abstract [en]

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFN beta)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFN beta-1a subcutaneous and IFN beta-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFN beta-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFN beta therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFN beta in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFN beta. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:kth:diva-197775 (URN)10.1371/journal.pone.0162752 (DOI)000386715500005 ()27806057 (PubMedID)2-s2.0-84994274854 (Scopus ID)
Note

QC 20161228

Available from: 2016-12-28 Created: 2016-12-08 Last updated: 2017-11-29Bibliographically approved
Ramanujam, R., Hillert, J. & Manouchehrinia, A. (2016). Predicting conversion to secondary progressive multiple sclerosis using a clinical decision tree. Paper presented at 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND. Multiple Sclerosis, 22, 454-454
Open this publication in new window or tab >>Predicting conversion to secondary progressive multiple sclerosis using a clinical decision tree
2016 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, p. 454-454Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Sage Publications, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:kth:diva-204143 (URN)000383267202098 ()
Conference
32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), SEP 14-17, 2016, London, ENGLAND
Note

QC 20170330

Available from: 2017-03-30 Created: 2017-03-30 Last updated: 2017-11-29Bibliographically approved
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