The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort
Abstract
OBJECTIVE: To define the rate, timing, and clinical risk factors for the development of autoimmune disease (AID) after alemtuzumab treatment for multiple sclerosis (MS). METHODS: We analyzed prospective clinical and serologic data from 248 patients with MS treated with alemtuzumab, with median follow-up of 34.3 months (range 6.7-107.3). RESULTS: Novel AID developed in 22.2%. Thyroid AID was most frequent (15.7%). A range of hematologic, renal, and dermatologic AID were also observed as was asymptomatic development of novel autoantibodies. AID was seen from 2 weeks after initial treatment and was most frequent 12-18 months after first treatment. No new cases of AID were identified 60 months or more after initial treatment and risk of AID was independent of total alemtuzumab dose or interval of dosage. While established risk factors for AID including sex and age had no impact on AID frequency, both family history (odds ratio = 7.31, 95% confidence interval 3.02-17.68) of AID and a personal smoking history (odds ratio = 3.05, 95% confidence interval 1.50-6.19) were predictive of AID expression. CONCLUSIONS: Cumulative risk for AID in MS following alemtuzumab is 22.2%, most frequent between 12 and 18 months following first dose and evident for up to 5 years. Individual risk is modified by smoking and family history, which should be incorporated within the counseling process prior to treatment. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the risk of AID after alemtuzumab treatment for MS is time-limited and modified by external factors.
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“while others did not [12, 77].”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [77]
In the citing paper
“In the studies that have, most patients responded to antithyroid drugs (ATDs) [1214, 50, 77], at least initially.”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [77]
In the citing paper
“In contrast, requirements for RAI or surgery were lower than expected in conventional GD in some reports; 14% [14], 27% [77].”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [77]
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Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism
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BackgroundAlemtuzumab for the treatment of multiple sclerosis
Evan, J. R., Bozkurt, S. B., Thomas, N. C., & Bagnato, F. R. (2018) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1425388 · Cited by 34
Rajasundaram, S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00402 · Cited by 37
“Furthermore, CXCL1 mAb therapies could offer a more precise therapeutic alternative to alemtuzumab, which, while unprecedentedly efficacious, also causes severe immunosuppression that can lead to acquired autoimmune deficiency (79).”
BackgroundThe Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis
Rolla, S., Maglione, A., Mercanti, S. F. D., & Clerico, M. (2020) · Cells · doi:10.3390/cells9061396 · Cited by 36
“The individual risk is threefold higher in smokers and sevenfold greater in patients wo have a family history, there are non-conclusive certainties regarding the role of sex as risk factor [72].”
BackgroundTreatment of Hemophagocytic Lymphohistiocytosis With Alemtuzumab in Systemic Lupus Erythematosus
Keith, M. P., Pitchford, C. W., & Bernstein, W. B. (2012) · JCR Journal of Clinical Rheumatology · doi:10.1097/rhu.0b013e31824e8d9b · Cited by 34
“Furthermore, despite its successful use in multiple sclerosis compared with interferon A1a,(26) the development of autoimmune disease following alemtuzumab in these patients warrants further examination.(27) To our knowledge, this is the first report of SLE-induced HLH successfully treated with alemtuzumab.”
MethodImmune regulation by CD52-expressing CD4 T cells
Toh, B., Kyaw, T. S., Tipping, P. G., & Bobik, A. (2013) · Cellular and Molecular Immunology · doi:10.1038/cmi.2013.35 · Cited by 34
Autoimmune Thyroid Disease in the Use of Alemtuzumab for Multiple Sclerosis: A Review
Aranha, A. A., Amer, S., Reda, E. S., Broadley, S., & Davoren, P. M. (2013) · Endocrine Practice · doi:10.4158/ep13020.ra · Cited by 35
A remarkable effect of alemtuzumab in a patient suffering from narcolepsy with cataplexy
Donjacour, C. E. H. M., & Lammers, G. J. (2011) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2011.00985.x · Cited by 34
“By binding to the CD52, it causes lysis of lymphocytes, and subsequently a differential recovery of lymphocyte subsets with prolonged suppression of CD4 T-cells (Cossburn et al., 2011).”
BackgroundInfluentialPfeuffer, S., Ruck, T., Pul, R., Rolfes, L., Korsukewitz, C., Pawlitzki, M., Wildemann, B., Klotz, L., Kleinschnitz, C., Scalfari, A., et al. (2021) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-325304 · Cited by 32
Advancing drug delivery systems for the treatment of multiple sclerosis
Tabansky, I., Messina, M. D., Bangeranye, C., Goldstein, J., Blitz-Shabbir, K. M., Machado, S., Jeganathan, V., Wright, P., Najjar, S., Cao, Y., et al. (2015) · Immunologic Research · doi:10.1007/s12026-015-8719-0 · Cited by 32
Hands on Alemtuzumab-experience from clinical practice: whom and how to treat
Hassoun, L., Eisele, J., Thomas, K., & Ziemssen, T. (2016) · Multiple Sclerosis and Demyelinating Disorders · doi:10.1186/s40893-016-0011-1 · Cited by 31
Long, Y., Zheng, Y., Chen, M., Zhang, B., Gao, C., Shan, F., Yang, N., & Fan, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100672 · Cited by 30
“Previous studies indicated that treatment of MS with interferon and alemtuzumab were associated with the development of other autoimmune disorders [24,25,26,27].”
ResultNovel Immunomodulatory Approaches for the Management of Multiple Sclerosis
Kantarci, O. H., Pirko, I., & Rodriguez, M. (2013) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2013.196 · Cited by 26
Anti-T-cell antibodies for the treatment of acute rejection after renal transplantation
van den Hoogen, M. W. F., Hoitsma, A. J., & Hilbrands, L. B. (2012) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2012.689278 · Cited by 27
“Treatment of multiple sclerosis patients with alemtuzumab is associated with an increased incidence of secondary autoimmune disease, especially of the thyroid gland [47].”
BackgroundOcular Findings in Alemtuzumab (Campath-1H)-induced Thyroid Eye Disease
Trinh, T., Haridas, A. S., & Sullivan, T. J. (2015) · Ophthalmic Plastic and Reconstructive Surgery · doi:10.1097/iop.0000000000000310 · Cited by 26
Immunotherapy of Multiple Sclerosis
Karussis, D. M. (2013) · BioDrugs · doi:10.1007/s40259-013-0011-z · Cited by 26
Subcutaneous Recombinant Interferon-β-1a (Rebif®)
Sanford, M., & Lyseng-Williamson, K. A. (2011) · Drugs · doi:10.2165/11207540-000000000-00000 · Cited by 25
Roos, J. C. P., Moran, C., Chatterjee, K., Jones, J., Coles, A. J., & Murthy, R. (2018) · Eye · doi:10.1038/s41433-018-0282-1 · Cited by 26
Acute respiratory distress syndrome following alemtuzumab therapy for relapsing multiple sclerosis
Keh, R. Y. S., Jackson, F., Sharaf, N., Mihalova, T., Talbot, P. R., Rog, D. J., & Pace, A. (2017) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2017.03.001 · Cited by 24
Sheth, V., Potter, V. T., Gandhi, S., Kulasekararaj, A. G., de Lavallade, H., Muus, P., Pagliuca, A., Rice, C., Mehra, V., Grimaldi, F., et al. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019000480 · Cited by 25
Biological Drugs in Guillain-Barré Syndrome: An Update
Motamed-Gorji, N., Matin, N., Tabatabaie, O., Pavone, P., Romano, C., Falsaperla, R., & Vitaliti, G. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666161213114904 · Cited by 23
“disorders following treatment of MS with Alemtuzumab to be 22% [71].”
BackgroundAlemtuzumab Induced Thyroid Disease in Multiple Sclerosis: A Review and Approach to Management
Mahzari, M., Arnaout, A., & Freedman, M. S. (2015) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2015.48 · Cited by 26
“reported that only 28% of patients with AITD GD required radioactive iodine (RAI) due to failure of medical treatment.(21) In the CAMMS223 trial, 36.”
InfluentialImmune Reconstitution Inflammatory Syndrome Associated with Biologic Therapy
Gupta, M., Jafri, K., Sharim, R. R., Silverman, S., Sindher, S., Shahane, A., & Kwan, M. (2014) · Current Allergy and Asthma Reports · doi:10.1007/s11882-014-0499-4 · Cited by 21
Obermann, M., Ruck, T., Pfeuffer, S., Baum, J., Wiendl, H., & Meuth, S. G. (2016) · Multiple Sclerosis Journal · doi:10.1177/1352458516638558 · Cited by 20
Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients
Rauma, I., Mustonen, T., Seppä, J. M., Ukkonen, M., Männikkö, M., Verkkoniemi‐Ahola, A., Kartau, M., Saarinen, J. T., Luostarinen, L., Simula, S., et al. (2021) · Journal of Neurology · doi:10.1007/s00415-021-10664-w · Cited by 19
Subei, A. M., & Ontaneda, D. (2015) · CNS Drugs · doi:10.1007/s40263-015-0277-4 · Cited by 19
Lambert–Eaton myasthenic syndrome associated with alemtuzumab administration
Hoffman, B. M., Zeid, N. E. A., Alam, U., & Caress, J. B. (2018) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2018.10.015 · Cited by 18
Williams, K. M., Dietzen, D., Hassoun, A. A., Fennoy, I., & Bhatia, M. (2014) · Pediatric Blood & Cancer · doi:10.1002/pbc.25102 · Cited by 18
“The greatest risk of autoimmune disease appears to be in the 12–36 months period following the initial alemtuzumab infusion [16] with some reporting an increased incidence up to 5 years after treatment [17].”
BackgroundSovetkina, A., Nadir, R., Scalfari, A., Tona, F., Murphy, K. G., Rigoni, E., Dorsey, R., Malik, O., Nandoskar, A., Singh‐Curry, V., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa453 · Cited by 21
Alemtuzumab for the treatment of multiple sclerosis
Willis, M., & Robertson, N. (2015) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s80112 · Cited by 17
“59 In the Cambridge open label long-term follow-up study, total AID occurred in 48% of treated patients with thyroid autoimmunity observed in 41% of patients.”
InfluentialDubey, D., Kieseier, B. C., Hartung, H. P., Hemmer, B., Miller-Little, W. A., & Stüve, O. (2014) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2015.992881 · Cited by 16
“The increased incidence of autoimmune disorders following alemtuzumab could be attributed to depletion of regulatory T cells, leading to a B-cell reconstitution that is skewed toward proinflammatory cell subsets [41].”
Background
Metadata
- Authors
- Cossburn, M., Pace, A. A., Jones, J., Ali, R., Ingram, G., Baker, K., Hirst, C., Zajicek, J., Scolding, N., Boggild, M., Pickersgill, T., Ben-Shlomo, Y., Coles, A., & Robertson, N. P.
- Affiliations
- University of Cambridge (GB)
- From the Department of Psychological Medicine and Neurology (M.C., G.I., K.B., C.H., T.P., N.P.R.), Cardiff University, University Hospital of Wales, Heath Park, Cardiff, UK; Department of Neurology (A.A.P., J.Z.), Penninsula Medical School, Tamar Science Park, Derriford, Plymouth; Neurology Unit (J.J., A.C.), Department of Clinical Neurosciences, Cambridge University, Addenbrooke's Hospital, Cambridge; Department of Neurology (R.A., M.B.), The Walton Centre NHS Foundation Trust, Fazakerley,...
- Venue
- Neurology
- Published
- 2011-08-09
- Volume
- 77
- Issue
- 6
- Pages
- 573-579
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2110867277
- Cited by
- 216
- References
- 23
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 11 · 2022: 11 · 2021: 7 · 2020: 10 · 2019: 18 · 2018: 17 · 2017: 16 · 2016: 25 · 2015: 14 · 2014: 19 · 2013: 22 · 2012: 23
- FWCI
- 15.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- National Institute for Health and Care Research (CL-2008-14-004)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- alemtuzumab, multiple sclerosis, autoimmune disease, thyroid autoimmunity, smoking, family history (medicine), risk factors, treatment safety
- MeSH terms
- Alemtuzumab, Adolescent, Adult, Aged, Anti-Inflammatory Agents, Antibodies, Monoclonal, Antibodies, Neoplasm, Antineoplastic Agents, Autoantibodies, Autoimmune Diseases, Counseling, Female, Follow-Up Studies, Humans, Male, Methylprednisolone, Middle Aged, Multiple Sclerosis, Prospective Studies, Risk Factors, Smoking, Thyroid Diseases, Cohort Studies, Treatment Outcome, Young Adult, Antibodies, Monoclonal, Humanized
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