DOCSLIB.ORG

Delayed Allergic Reaction to Natalizumab Associated with Early Formation of Neutralizing Antibodies

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Delayed Allergic Reaction to Natalizumab Associated with Early Formation of Neutralizing Antibodies OBSERVATION Delayed Allergic Reaction to Natalizumab Associated With Early Formation of Neutralizing Antibodies Markus Krumbholz, MD; Hannah Pellkofer, MD; Ralf Gold, MD; Lisa Ann Hoffmann, MD; Reinhard Hohlfeld, MD; Tania Ku¨mpfel, MD Background: Natalizumab is a new therapeutic option exanthema, and a swollen lower lip during several days for relapsing-remitting multiple sclerosis. As with other an- after his second infusion of natalizumab. tibody therapies, hypersensitivity reactions have been ob- served. In the Natalizumab Safety and Efficacy in Relapsing- Results: The patient developed a delayed, serum sick- RemittingMultipleSclerosis(AFFIRM)trial,infusion-related ness–like, type III systemic allergic reaction to natali- hypersensitivity reactions developed in 4% of patients, usu- zumab. Five weeks after initiation of this therapy, he tested ally within 2 hours after starting the infusion. positive for antinatalizumab antibodies and exhibited persistent antibody titers 8 and 12 weeks later. His symp- Objective: To report a significant, delayed, serum sick- toms completely resolved with a short course of oral ness–like, type III systemic allergic reaction to natali- glucocorticosteroids. zumab. Conclusion: Clinicians and patients should be alert not Design: Case report describing clinical follow-up and only to immediate but also to significantly delayed sub- the serial measurement of antinatalizumab antibodies. stantial allergic reactions to natalizumab. Patient: A 23-year-old man with relapsing-remitting mul- tiple sclerosis developed a fever, arthralgias, urticarial Arch Neurol. 2007;64(9):1331-1333 ATALIZUMAB IS A MONO- resulting in severe gait ataxia (Expanded clonal antibody targeting Disability Status Scale, 5.5). Previous treat- ␣ 4 integrin. It is highly ef- ments included steroid pulses for relapses fective in reducing the re- and 44 µg of interferon beta-1a 3 times lapse rate and disease pro- weekly. Interferon therapy was discontin- gressioninpatientswithrelapsing-remitting ued after 1 year because of insufficient ef- N 1 multiple sclerosis and was approved by the ficacy. The first dose of natalizumab was US Food and Drug Administration in June given 24 days later. The patient did not re- 2006 as monotherapy given intravenously port any adverse reactions within 2 hours every 4 weeks. Adverse effects include pro- after the first and second infusions. On both gressive multifocal leukoencephalopathy occasions there were no immediate adverse in about 0.1% and systemic allergic reac- effects and the patient returned home. Eight tions in about 4% of treated patients. Hy- hours after the second infusion, however, persensitivityreactionsusuallyoccurwithin he collapsed and developed a fever of up 1 hour after the infusion of natalizumab and to 39.4°C. Initially, he thought he had ac- frequently concur with the second infusion. quired a viral infection and therefore did Here we describe a patient who pre- not seek medical advice. His body tempera- sented to us 6 days after the second dose ture returned to normal, but 3 days later an of natalizumab with a substantial sys- itching rash appeared on his thighs and temic allergic reaction. Subsequently, he chest. Another 3 days later, his lower lip Author Affiliations: Institute tested permanently positive for antibod- swelled and the general practitioner referred for Clinical Neuroimmunology, ies against natalizumab. the patient back to our outpatient clinic. Ludwig Maximilian University, The patient reported arthralgias and a Munich, Germany feeling like he had a swollen tongue and (Drs Krumbholz, Pellkofer, REPORT OF A CASE Hoffmann, Hohlfeld, and throat. On examination, there was an ur- Ku¨ mpfel); and Department of ticarial erythema accentuated on his thighs Neurology, St Josef-Hospital, A 23-year-old white man was treated with and chest. His lower lip was swollen Ruhr University, Bochum, natalizumab for severe relapsing-remitting (Figure 1). His concurrent medications Germany (Dr Gold). multiple sclerosis with recurrent myelitis had been unchanged during the past (REPRINTED) ARCH NEUROL / VOL 64 (NO. 9), SEP 2007 WWW.ARCHNEUROL.COM 1331 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 A First mitoxantrone dose 3 2 Presentation with allergic symptoms 1 Antinatalizumab Antibodies, µg/mL 0 Second natalizumab dose 04812 16 Time After First Dose of Natalizumab, wk Figure 2. Time course of antibodies against natalizumab. Antibodies were B measured by sandwich enzyme-linked immunosorbent assay in serum samples obtained as indicated immediately before the second dose of natalizumab, at peak of symptoms when the patient presented in our outpatient clinic (6 days after the second dose of natalizumab), immediately before the first dose of mitoxantrone, and 21 days after mitoxantrone. Whiskers indicate SDs of triplicates. The dotted line indicates the cutoff for antibody-positive samples at 0.5 µg/mL. zumab antibodies in this patient was similar to other pa- tients who have tested positive for antibodies against na- talizumab. COMMENT This patient showed a delayed allergic reaction that de- veloped during several days after the second infusion of natalizumab. Tests were persistently positive for antina- talizumab antibodies as early as 5 weeks after the first dose. Most previously reported hypersensitivity reac- tions to natalizumab occurred within in the first 2 hours after infusion. By contrast, our patient developed symp- toms gradually during several days. Because we could not detect any other cause for this hypersensitivity reaction, a causal relationship with the second natalizumab infu- sion is very likely. So far, typical infusion-related allergic reactions after natalizumab treatment include anaphylactoid hyper- sensitivity reactions with urticaria,2 allergic dermatitis,2 flushing, headache, and hypotension. These symptoms occurred within 2 hours after infusion and would be classified as type I allergic reactions. However, in our Figure 1. Swollen lower lip (A) and erythema on the right thigh (B) case, the clinical course points to a serum sickness–type documented in a 23-year-old patient with multiple sclerosis 6 days after his reaction (type III), because symptoms progressed dur- second dose of natalizumab. ing several days. Three cases (2 patients in treatment groups, 1 patient in a placebo group, each at a single weeks. He had no history of allergic reactions. After ex- study center) of serum sickness were noted in the phase cluding infectious causes, we started treatment with 2 trial of natalizumab in multiple sclerosis,3 but no fur- 60 mg of prednisolone orally for 2 days; all symptoms ther information about the time course, symptoms, or disappeared in the subsequent days. We diagnosed a de- treatment of these patients was provided. Serum sick- layed allergic reaction, discontinued natalizumab, and ini- ness has also been described in association with other tiated mitoxantrone therapy after 8 weeks instead. monoclonal antibody therapies, including chimeric an- Evaluation of antinatalizumab antibodies by stan- tibodies, such as infliximab4 and rituximab,5 as well as dard sandwich enzyme-linked immunosorbent assay1 re- humanized antibodies, such as alemtuzumab.6 In one vealed that the patient had seroconverted after the sec- study with infliximab in patients with Crohn disease, ond dose of natalizumab. The number of antibodies rose serum sickness occurred in 2.8% of patients, indicating further during the following 8 weeks until the first dose that type III allergic reactions may be more frequent of mitoxantrone, when they started to decrease slightly with chimeric monoclonal antibodies than with hu- (Figure 2). The order of magnitude of the antinatali- manized monoclonal antibodies.7 (REPRINTED) ARCH NEUROL / VOL 64 (NO. 9), SEP 2007 WWW.ARCHNEUROL.COM 1332 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Data from the Natalizumab Safety and Efficacy in Re- Pellkofer, Gold, and Ku¨ mpfel. Analysis and interpreta- lapsing-Remitting Multiple Sclerosis (AFFIRM) trial point tion of data: Krumbholz and Ku¨ mpfel. Drafting of the manu- to an association of infusion-related reactions with the script: Krumbholz and Ku¨ mpfel. Critical revision of the presence of antinatalizumab antibodies, as 68% of na- manuscript for important intellectual content: Pellkofer, talizumab-treated patients who had hypersensitivity re- Gold, Hoffmann, and Hohlfeld. Administrative, techni- actions were persistently positive for antibodies,2 whereas cal, and material support: Krumbholz. Study supervision: the incidence of persistent antibodies was 6% in the en- Hohlfeld and Ku¨ mpfel. tire treatment cohort. Financial Disclosure: Drs Gold and Hohlfeld have re- Antinatalizumab antibodies in patients with mul- ceived grant support and consultancy fees from Scher- tiple sclerosis have already been detected in 2 former stud- ing, Teva, Serono, and Biogen-Idec. ies as early as 4 weeks after a single natalizumab infu- Funding/Support: The Institute for Clinical Neuroim- sion.8,9 However, there are no data reported about adverse munology is supported by the Hermann and Lilly Schill- events or infusion-related reactions in these patients. ing Foundation, the Deutsche Forschungsgemeinschaft Our observation supports the view that hypersensi- (German Research Foundation) (Sonderforschungsbe- tivity reactions are associated with antibody formation reich 571 [Collaborative Research
Load more

Recommended publications
  • Anti-TNF Treatment in Inflammatory Bowel Disease
    xx xx 48 ANNALSJanuary OF GASTROENTEROLOGY 20, 2007, KIFISIA, A THENS2007, 20(1):48-53x, G xxREECE x Lecture Anti-TNF Treatment in Inflammatory Bowel Disease Suna Yapali, Hulya over Hamzaoglu INTRODUCTION disease than ulcerative colitis.2 Moreover, enhanced secre- tion of TNF-alpha from lamina propria mononuclear cells Crohn’s disease and ulcerative colitis are chronic in- has been found in the intestinal mucosa of IBD patients.3 flammatory disorders of the gastrointestinal tract. Although In Crohn’s disease tissues, TNF-alpha positive cells have the primary etiological defect stil remains unknown, in the been found deeper in the lamina propria and in the submu- last decade impotant progress has been made concerning cosa, whereas TNF-alpha immunoreactivity in ulcerative the immunological basis of the disease. Genetic, environ- colitis is, mostly, located in subepithelial macrophages.4 mental and microbial factors result in repeated activation There may be insufficient increased release of soluble TNF of mucosal immune response. Tumor necrosis factor alpha receptor from lamina propria mononuclear cells of patients (TNF-alpha) is one of the central cytokines in the under- with IBD in response to enhanced secretion of TNF-alpha.5 lying pathogenesis of mucosal inflammation in inflamma- TNF-alpha in the stool have also been found from children tory bowel disease (IBD) and has been the primary target with active IBD,6 and elevated levels of TNF-alpha have of biologic therapies. been found increased in the serum of children with active 7 Role of TNF-alpha in pathogenesis of ulcerative colitis and Crohn’s colitis. inflammatory bowel disease Anti-TNF antibodies and fusion proteins: TNF-alpha is produced by activated macrophages and We certainly have many ways to block TNF-alpha.
    [Show full text]
  • The Change of Fingolimod Patient Profiles Over Time
    Journal of Personalized Medicine Article The Change of Fingolimod Patient Profiles over Time: A Descriptive Analysis of Two Non-Interventional Studies PANGAEA and PANGAEA 2.0 Tjalf Ziemssen 1,* and Ulf Schulze-Topphoff 2 1 Zentrum für Klinische Neurowissenschaften, Universitätsklinikum Carl Gustav Carus, D-01307 Dresden, Germany 2 Novartis Pharma GmbH, D-90429 Nuremberg, Germany; [email protected] * Correspondence: [email protected] Abstract: (1) Background: Fingolimod (Gilenya®) was the first oral treatment for patients with relapsing-remitting multiple sclerosis (RRMS). Since its approval, the treatment landscape has changed enormously. (2) Methods: Data of PANGAEA and PANGAEA 2.0, two German real-world studies, were descriptively analysed for possible evolution of patient profiles and treatment behavior. Both are prospective, multi-center, non-interventional, long-term studies on fingolimod use in RRMS in real life. Data of 4229 PANGAEA patients (recruited 2011–2013) and 2441 PANGAEA 2.0 patients (recruited 2015–2018) were available. Baseline data included demographics, RRMS characteristics and disease severity. (3) Results: The mean age of PANGAEA and PANGAEA 2.0 patients was similar (38.8 vs. 39.2 years). Patients in PANGAEA 2.0 had shorter disease duration (7.1 vs. 8.2 years) and fewer relapses in the year before baseline (1.2 vs. 1.6). Disease severity at baseline estimated by Citation: Ziemssen, T.; EDSS and SDMT was lower in PANGAEA 2.0 patients compared to PANGAEA (EDSS difference Schulze-Topphoff, U. The Change of 1.0 points; SDMT difference 3.3 points). (4) Conclusions: The results hint at an influence of changes in Fingolimod Patient Profiles over the treatment guidelines and the label on fingolimod patients profiles over time.
    [Show full text]
  • Biologics in the Treatment of Lupus Erythematosus: a Critical Literature Review
    Hindawi BioMed Research International Volume 2019, Article ID 8142368, 17 pages https://doi.org/10.1155/2019/8142368 Review Article Biologics in the Treatment of Lupus Erythematosus: A Critical Literature Review Dominik Samotij and Adam Reich Department of Dermatology, University of Rzeszow, ul. Fryderyka Szopena 2, 35-055 Rzeszow, Poland Correspondence should be addressed to Adam Reich; adi [email protected] Received 7 May 2019; Accepted 18 June 2019; Published 18 July 2019 Academic Editor: Nobuo Kanazawa Copyright © 2019 Dominik Samotij and Adam Reich. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Systemic lupus erythematosus (SLE) is a chronic autoimmune infammatory disease afecting multiple organ systems that runs an unpredictable course and may present with a wide variety of clinical manifestations. Advances in treatment over the last decades, such as use of corticosteroids and conventional immunosuppressive drugs, have improved life expectancy of SLE suferers. Unfortunately, in many cases efective management of SLE is still related to severe drug-induced toxicity and contributes to organ function deterioration and infective complications, particularly among patients with refractory disease and/or lupus nephritis. Consequently, there is an unmet need for drugs with a better efcacy and safety profle. A range of diferent biologic agents have been proposed and subjected to clinical trials, particularly dedicated to this subset of patients whose disease is inadequately controlled by conventional treatment regimes. Unfortunately, most of these trials have given unsatisfactory results, with belimumab being the only targeted therapy approved for the treatment of SLE so far.
    [Show full text]
  • Monoclonal Antibodies — a Revolutionary Therapy in Multiple Sclerosis
    REVIEW ARTICLE Neurologia i Neurochirurgia Polska Polish Journal of Neurology and Neurosurgery 2020, Volume 54, no. 1, pages: 21–27 DOI: 10.5603/PJNNS.a2020.0008 Copyright © 2020 Polish Neurological Society ISSN 0028–3843 Monoclonal antibodies — a revolutionary therapy in multiple sclerosis Carmen Adella Sirbu1, 2, Magdalena Budisteanu1,3,4, Cristian Falup-Pecurariu5,6 1Titu Maiorescu University, Bucharest, Romania 2‘Dr. Carol Davila’ Central Military Emergency University Hospital, Clinic of Neurology, Bucharest, Romania 3‘Prof. Dr. Alex Obregia’ Clinical Hospital of Psychiatry, Psychiatry Research Laboratory, Bucharest, Romania 4‘Victor Babes’ National Institute of Pathology, Bucharest, Romania 5Faculty of Medicine, Transylvania University of Brașov, Brașov, Romania 6Department of Neurology, County Emergency Clinic Hospital, Brașov, Romania ABSTRACT Introduction. Multiple sclerosis (MS) has an increasing incidence and affects a young segment of the population, having a major impact on patients and consequently on society. The multifactorial aetiology and pathogenesis of this disease are incompletely known at present, but autoimmune aggression has a documented mechanism. State of the art. Since the 1990s, immunomodulatory drugs of high efficacy and a good safety profile have been launched. But the concept of NEDA (No Evidence of Disease Activity) remains the target to achieve. Thus, the new revolutionary class of monoclonal antibodies (moAbs) used in multiple medical fields, from this perspective represents a challenge even for multiple sclerosis, including the primary progressive form, for which there has been no treatment until recently. Clinical implications. In this article, we will review monoclonal antibodies’ use for MS, presenting their advantages and di- sadvantages, based on data accumulated since 2004 when the first monoclonal antibody was approved for active forms of the disease.
    [Show full text]
  • Updates in the Diagnosis and Treatment of Inflammatory Bowel Disease: Highlights from Digestive Disease Week 2011
    August 2011 www.clinicaladvances.com Volume 7, Issue 8, Supplement 13 Updates in the Diagnosis and Treatment of Inflammatory Bowel Disease: Highlights From Digestive Disease Week 2011 A Review of Selected Presentations From Digestive Disease Week 2011 May 7–10, 2011 Chicago, Illinois With commentary by: Gary R. Lichtenstein, MD Director, Inflammatory Bowel Disease Program Professor of Medicine University of Pennsylvania Philadelphia, Pennsylvania A CME Activity Approved for 1.0 AMA PRA Category 1 Credit(s)TM Release date: August 2011 Expiration date: August 31, 2012 Estimated time to complete activity: 1.0 hour Supported through an educational grant from UCB, Inc. Sponsored by Postgraduate Institute for Medicine Target Audience: This activity has been designed to meet the Pharmaceuticals, Proctor & Gamble, Prometheus Laboratories, Inc., Salix educational needs of gastroenterologists who treat patients with Pharmaceuticals, Santarus, Schering-Plough Corporation, Shire Pharma- Crohn’s disease (CD) and/or ulcerative colitis (UC). ceuticals, UCB, Warner Chilcotte, and Wyeth. He has also received funds for contracted research from Alaven, Bristol-Myers Squibb, Centocor Ortho Statement of Need/Program Overview: Various abstracts were Biotech, Ferring, Proctor & Gamble, Prometheus Laboratories, Inc., Salix presented at Digestive Disease Week 2011. Unfortunately, physicians cannot Pharmaceuticals, Shire Pharmaceuticals, UCB, and Warner Chilcotte. attend all of the poster sessions in their therapeutic area, and some physicians may have been unable
    [Show full text]
  • Middle-Level IM-MS and CIU Experiments for Improved
    bioRxiv preprint doi: https://doi.org/10.1101/2020.01.20.911750; this version posted January 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Middle-level IM-MS and CIU experiments for improved therapeutic immunoglobulin isotype fingerprinting Thomas Botzanowski1¶, Oscar Hernandez-Alba1¶, Martine Malissard2, Elsa Wagner-Rousset2, Evolène Deslignière1, Olivier Colas2, Jean-François Haeuw2, Alain Beck2, Sarah Cianférani1* 1 Laboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CNRS, IPHC UMR 7178, 67000 Stras- bourg, France. 2 IRPF - Centre d’Immunologie Pierre-Fabre (CIPF), 74160 Saint-Julien-en-Genevois, France. ABSTRACT: Currently approved therapeutic monoclonal antibodies (mAbs) are based on immunoglobulin G (IgG) 1, 2 or 4 iso- types, which differ in their specific inter-chains disulfide bridge connectivities. Different analytical techniques have been reported for mAb isotyping, among which native ion mobility mass spectrometry (IM-MS) and collision induced unfolding (CIU) experiments. However, mAb isotyping by these approaches is based on detection of subtle differences and thus remains challenging at the intact- level. We report here on middle-level (after IdeS digestion) IM-MS and CIU approaches to afford better differentiation of mAb isotypes. Our method provides simultaneously CIU patterns of F(ab’)2 and Fc domains within a single run. Middle-level CIU patterns of F(ab’)2 domains enable more reliable classification of mAb isotypes compared to intact level CIU, while CIU fingerprints of Fc domains are overall less informative for mAb isotyping. F(ab’)2 regions can thus be considered as diagnostic domains providing specific CIU signatures for mAb isotyping.
    [Show full text]
  • Reversibility of the Effects of Natalizumab on Peripheral Immune Cell Dynamics in MS Patients
    Reversibility of the effects of natalizumab on peripheral immune cell dynamics in MS patients Tatiana Plavina, PhD ABSTRACT Kumar Kandadi Objective: To characterize the reversibility of natalizumab-mediated changes in pharmacokinet- Muralidharan, PhD ics/pharmacodynamics in patients with multiple sclerosis (MS) following therapy interruption. Geoffrey Kuesters, PhD Methods: Pharmacokinetic/pharmacodynamic data were collected in the Safety and Efficacy of Daniel Mikol, MD, PhD Natalizumab in the Treatment of Multiple Sclerosis (AFFIRM) (every 12 weeks for 116 weeks) Karleyton Evans, MD and Randomized Treatment Interruption of Natalizumab (RESTORE) (every 4 weeks for 28 weeks) Meena Subramanyam, studies. Serum natalizumab and soluble vascular cell adhesion molecule–1 (sVCAM-1) were PhD measured using immunoassays. Lymphocyte subsets, a4-integrin expression/saturation, and vas- Ivan Nestorov, PhD cular cell adhesion molecule–1 (VCAM-1) binding were assessed using flow cytometry. Yi Chen, MS 3 Qunming Dong, PhD Results: Blood lymphocyte counts (cells/L) in natalizumab-treated patients increased from 2.1 9 3 9 Pei-Ran Ho, MD 10 to 3.5 10 . Starting 8 weeks post last natalizumab dose, lymphocyte counts became 3 Diogo Amarante, MD significantly lower in patients interrupting treatment than in those continuing treatment (3.1 9 3 9 p 5 Alison Adams, PhD 10 vs 3.5 10 ; 0.031), plateauing at prenatalizumab levels from week 16 onward. All a Jerome De Sèze, MD measured cell subpopulation, 4-integrin expression/saturation, and sVCAM changes demon- Robert Fox, MD strated similar reversibility. Lymphocyte counts remained within the normal range. Ex vivo z Ralf Gold, MD VCAM-1 binding to lymphocytes increased until 16 weeks after the last natalizumab dose, Douglas Jeffery, MD then plateaued, suggesting reversibility of immune cell functionality.
    [Show full text]
  • The Effect of Certolizumab Drug Concentration and Anti-Drug Antibodies on TNF Neutralisation L.C
    The effect of certolizumab drug concentration and anti-drug antibodies on TNF neutralisation L.C. Berkhout1, E.H. Vogelzang2, M.H. Hart1, F.C. Loeff1, L. Dijk1, N.I.L. Derksen1, R. Wieringa3, W.A van Leeuwen3, C.L.M. Krieckaert2, A. de Vries3, M.T. Nurmohamed2,4, G.J. Wolbink1,2, T. Rispens1 1Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands, and Landsteiner Laboratory, Amsterdam UMC, Academic Medical Centre, University of Amsterdam, The Netherlands; 2Amsterdam Rheumatology and immunology Center | Reade, Amsterdam, The Netherlands; 3Biologics Lab, Sanquin Diagnostic Services, Amsterdam, The Netherlands; 4Amsterdam Rheumatology and immunology Center | Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands. Abstract Objective Tumour necrosis factor (TNF) inhibitors like certolizumab, elicit an immunogenic response leading to the formation of anti-drug antibodies (ADAs). We sought to mechanistically investigate the relationship between certolizumab concentrations, ADAs, and the effective TNF neutralising capacity in sera of rheumatoid arthritis (RA) patients. TNF neutralising capacity of certolizumab was compared to the neutralising capacity of adalimumab. Methods Serum samples were collected from 40 consecutive certolizumab-treated RA patients at baseline and 4, 16, 28 and 52 weeks after treatment initiation [Dutch Trial Register NTR (Nederlands Trial Register) Trial NL2824 no. 2965]. Certolizumab concentration and ADA titre were measured with a certolizumab bridging enzyme-linked immunosorbent assay (ELISA) and a drug-tolerant radioimmunoassay (RIA), respectively. TNF neutralisation by certolizumab and adalimumab, in presence or absence of ADAs, was analysed with the TNF-sensitive WEHI bioassay. Results Despite a high incidence of ADAs during one year of follow-up (65%; 26/40 patients), certolizumab levels of >10 μg/ml were measured in most patients.
    [Show full text]
  • Natalizumab: Perspectives from the Bench to Bedside
    Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Natalizumab: Perspectives from the Bench to Bedside Afsaneh Shirani1 and Olaf Stüve1,2 1Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 2Neurology Section, VA North Texas Health Care System, Medical Service Dallas, VA Medical Center, Dallas, Texas 75216 Correspondence: [email protected] Probably no other disease-modifying drug for multiple sclerosis has a more fascinating story than natalizumab from both the bench to bedside perspective and the postmarketing experi- ence standpoint. Natalizumab is a monoclonal antibody that inhibits the trafficking of lympho- cytes from the blood into the central nervous system by blocking the adhesion molecule α4-integrin. Natalizumab was approved as a disease-modifying drug for relapsing remitting multiple sclerosis only 12 years after the discovery of its target molecule—atimeline that is rather fast for drug development. However, a few months after its U.S. Food and Drug Administration approval, natalizumab was withdrawn from the market because of an unanticipated complication—progressive multifocal leukoencephalopathy. It was later rein- stated with required adherence to a strict monitoring program and incorporation of mitigation strategies. he development of therapeutic monoclonal aspects related to natalizumab use in clinical Tantibodies shows the importance of a target- practice. centered approach to modify the course of mul- tiple sclerosis (MS) (Buttmann and Rieckmann DISCOVERY AND MECHANISM OF ACTION 2008). Natalizumab is the first monoclonal an- www.perspectivesinmedicine.org tibody approved for the treatment of relapsing Natalizumab (Tysabri, Biogen Idec, Cambridge, MS after convincingly showing clinically and MA) is a humanized recombinant immuno- radiologically significant effects in phase III tri- globulin (Ig)G4 monoclonal antibody that als (Stüve and Bennett 2007).
    [Show full text]
  • Since January 2020 Elsevier Has Created a COVID-19 Resource Centre with Free Information in English and Mandarin on the Novel Coronavirus COVID- 19
    Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Multiple Sclerosis and Related Disorders 39 (2020) 102073 Contents lists available at ScienceDirect Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard Commentary The COVID-19 pandemic and the use of MS disease-modifying therapies T ⁎ Gavin Giovannonia, , Chris Hawkesa, Jeannette Lechner-Scottb, Michael Levyc, Emmanuelle Waubantd, Julian Golda,e a Blizard Institute, Barts and The London School of Medicine and Dentistry, 4 Newark Street, London, E1 2AT, UK b School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia c NMO Clinic and Research Laboratory, Division of Neuroimmunology & Neuroinfectious Disease, Massachusetts General Hospital, Boston, USA d Department of Neurology, UC San Francisco, San Francisco, California, USA e The Albion Centre, Prince of Wales Hospital, Sydney, New South Wales, Australia Maria was distraught after reading about the ‘potential’ epidemic, yet It is clear that COVID-19 is a pandemic and global health crisis with to happen, and the horror stories on Facebook needing reassurance and the potential to kill millions of people, particularly the elderly and people certainty about what she should do.
    [Show full text]
  • INN Working Document 05.179 Update 2011
    INN Working Document 05.179 Update 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) INN Working Document 05.179 Distr.: GENERAL ENGLISH ONLY 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Essential Medicines and Pharmaceutical Policies (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) © World Health Organization 2011 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]
  • Natalizumab for the Treatment of Relapsing-Remitting Multiple Sclerosis
    Natalizumab for the treatment of relapsing-remitting multiple sclerosis Systematic review Endbericht Project Report No.: 112 ISSN: 1992-0488 ISSN-online: 1992-0496 Natalizumab for the treatment of relapsing-remitting multiple sclerosis Systematic Review Endbericht Vienna, Februar 2019 Project team Projectleader: Mag. Dr. Eva Fuchs Author: Mag. Dr. Eva Fuchs Project support Systematic literature search: Mag. Dr. Eva Fuchs External review: Ao Univ. Prof. PD Dr. Siegrid Fuchs OA Dr. Sabine Urbanits, MSc, MA Internal review: Dr. Ingrid Zechmeister-Koss, MA Correspondence: Mag. Dr. Eva Fuchs, [email protected] This report should be referenced as follows: Fuchs E. Natalizumab for the treatment of relapsing-remitting multiple sclerosis. LBI-HTA Projektbericht Nr.: 112; Jahr 2019. Wien: Ludwig Boltzmann Institut für Health Technology Assessment. Conflict of interest All authors and the reviewers involved in the production of this report have declared they have no conflicts of interest in relation to the technology assessed according to the Uniform Requirements of Manuscripts Statement of Medical Journal Editors (www.icmje.org). Disclaimer The external reviewers did not co-author the scientific report and do not necessarily all agree with its content. Only the LBI-HTA is responsible for errors or omissions that could persist. The final version and the policy recommendations are under the full responsibility of the LBI-HTA. CONTENT INFORMATION Publisher: Ludwig Boltzmann Gesellschaft GmbH Nußdorferstr. 64, 6 Stock, A-1090 Wien https://hta.lbg.ac.at/page/imprint Responsible for content: Ludwig Boltzmann Institute for Health Technology Assessment (LBI-HTA) Garnisongasse 7/20, A-1090 Vienna https://hta.lbg.ac.at/ Project reports of the LBI-HTA do not appear on a regular basis and serve to publicise the research results of the Ludwig Boltzmann Institute of Health Technology Assessments.
    [Show full text]