Journal ArticleDOI
Progressive Multifocal Leukoencephalopathy in a Patient With Progressive Multiple Sclerosis Treated With Ocrelizumab Monotherapy.
Arpan Patel,James Sul,Marc L. Gordon,Jared Steinklein,Shayna Sanguinetti,Bidyut Pramanik,Dushyant P. Purohit,Vahram Haroutunian,Vahram Haroutunian,Alex K. Williamson,Igor J. Koralnik,Asaff Harel +11 more
Reads0
Chats0
TLDR
In this article, the authors reported the first case of progressive multifocal leukoencephalopathy (PML) occurring with ocrelizumab monotherapy in a patient with progressive multiple sclerosis without prior immunomodulation.Abstract:
Importance Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by the JC virus that has no proven effective treatment. Although rare cases of PML have occurred with other anti-CD20 therapies, there had been no prior cases associated with ocrelizumab. Objective To report the first ever case of PML occurring with ocrelizumab monotherapy in a patient with progressive multiple sclerosis without prior immunomodulation. Design, Setting, and Participant This case was reported from an academic medical center. The patient had multiple sclerosis while receiving ocrelizumab monotherapy. Exposures Ocrelizumab monotherapy. Results A 78-year-old man with progressive multiple sclerosis treated with ocrelizumab monotherapy for 2 years presented with 2 weeks of progressive visual disturbance and confusion. Examination demonstrated a right homonymous hemianopia, and magnetic resonance imaging revealed an enlarging nonenhancing left parietal lesion without mass effect. Cerebrospinal fluid revealed 1000 copies/mL of JC virus, confirming the diagnosis of PML. Blood work on diagnosis revealed grade 2 lymphopenia, with absolute lymphocyte count of 710/μL, CD4 of 294/μL (reference range, 325-1251/μL), CD8 of 85/μL (reference range, 90-775/μL), CD19 of 1/μL, preserved CD4/CD8 ratio (3.45), and negative HIV serology. Retrospective absolute lymphocyte count revealed intermittent grade 1 lymphopenia that preceded ocrelizumab (absolute lymphocyte count range, 800-1200/μL). The patient’s symptoms progressed over weeks to involve bilateral visual loss, right-sided facial droop, and dysphasia. Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated. The patient nevertheless declined rapidly and ultimately died. PML was confirmed at autopsy. Conclusions and Relevance In this case report, PML occurrence was likely a result of the immunomodulatory function of ocrelizumab as well as age-related immunosenescence. This case report emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections such as elderly patients.read more
Citations
More filters
Journal ArticleDOI
Anti-CD20 therapies for multiple sclerosis: current status and future perspectives.
TL;DR: In this article, the authors provide an updated overview of the involvement of B-cells in the immune pathophysiology and pathology of MS and summarize the rationale regarding the use of anti-CD20 therapies and the results of the main randomized controlled trials and observational studies.
Journal ArticleDOI
Progress in the Application of Drugs for the Treatment of Multiple Sclerosis
TL;DR: In this article, the authors summarized the recent application of drugs used in MS treatment, mainly introducing new drugs with immunomodulatory, neuroprotective or regenerative properties and their possible treatment strategies for MS.
Journal ArticleDOI
Clinical Perspectives on the Molecular and Pharmacological Attributes of Anti-CD20 Therapies for Multiple Sclerosis
TL;DR: In this article, a review of anti-CD20 monoclonal antibody therapies for the treatment of multiple sclerosis is presented, with the potential implications of differences in molecular structures, target epitopes, dosing regimens, mechanisms and impact on B-cell depletion and reconstitution, immunogenicity, administration-related reactions, and infection risks.
Journal ArticleDOI
Disease-modifying therapies and progressive multifocal leukoencephalopathy in multiple sclerosis: A systematic review and meta-analysis.
Shitiz Sriwastava,Saurabh Kataria,Samiksha Srivastava,Shaghayegh Kazemlou,Si Gao,Sijin Wen,Hamidreza Saber,Richa Tripathi,Zubeda Sheikh,Sarah Peterson,Ronald Gwinn,Evanthia Bernitsas +11 more
TL;DR: In this paper, a literature review and meta-analysis of 194 patients from 62 articles in PubMed, SCOPUS and EMBASE was conducted to investigate prognostic factors that can determine outcome in MS-related leukoencephalopathy patients.
Journal ArticleDOI
Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis.
Maria Cellerino,Giacomo Boffa,Caterina Lapucci,Francesco Tazza,Elvira Sbragia,Elisabetta Mancuso,Nicolò Bruschi,Simona Minguzzi,Federico Ivaldi,Ilaria Poire,Alice Laroni,Gianluigi Mancardi,Elisabetta Capello,Antonio Uccelli,Giovanni Novi,Matilde Inglese,Matilde Inglese +16 more
TL;DR: In this article, the authors provided effectiveness and safety data of ocrelizumab treatment in patients with relapsing-remitting (RR-) and progressive multiple sclerosis (PMS) and evaluated clinical and immunological predictors of early treatment response.
References
More filters
Journal ArticleDOI
Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis
Xavier Montalban,Stephen L. Hauser,Ludwig Kappos,Douglas L. Arnold,Amit Bar-Or,Giancarlo Comi,Jérôme De Seze,Gavin Giovannoni,Hans-Peter Hartung,Bernhard Hemmer,Fred D. Lublin,Kottil Rammohan,Krzysztof Selmaj,Anthony Traboulsee,Annette Sauter,Donna Masterman,Paulo Fontoura,Shibeshih Belachew,Hideki Garren,N. Mairon,Peter Chin,Jerry S. Wolinsky +21 more
TL;DR: Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections.
Journal ArticleDOI
Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
Stephen L. Hauser,Amit Bar-Or,Giancarlo Comi,Gavin Giovannoni,Hans Peter Hartung,Bernhard Hemmer,Fred D. Lublin,Xavier Montalban,Kottil Rammohan,Krzysztof Selmaj,A. Traboulsee,Jerry S. Wolinsky,Douglas L. Arnold,Gaelle Klingelschmitt,Donna Masterman,Paulo Fontoura,Shibeshih Belachew,Peter Chin,N. Mairon,Hideki Garren,Ludwig Kappos +20 more
TL;DR: Among patients with relapsing multiple sclerosis, ocrelizumab was associated with lower rates of disease activity and progression than interferon beta‐1a over a period of 96 weeks.
Journal ArticleDOI
Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy
Irene Cortese,Pawel Muranski,Yoshimi Enose-Akahata,Seung-Kwon Ha,Bryan Smith,MariaChiara Monaco,Caroline F. Ryschkewitsch,Eugene O. Major,Joan Ohayon,Matthew K. Schindler,Erin S Beck,Lauren B. Reoma,Steve Jacobson,Daniel S. Reich,Avindra Nath +14 more
TL;DR: These findings are consistent with the hypothesis that in some patients with PML, pembrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against the JC virus.
Journal ArticleDOI
Immunosenescence: deficits in adaptive immunity in the elderly
F. T. Hakim,R. E. Gress +1 more
TL;DR: These age-associated immune dysfunctions are the consequence of declines in both the generation of new naïve T and B lymphocytes and the functional competence of memory populations, and are termed immunosenescence.
Journal ArticleDOI
The natural history of primary progressive multiple sclerosis.
TL;DR: Previous analyses in an updated PPMS retrospective cohort study of prevalent cases identified 2 predictors of a slower disease progression in primary progressive multiple sclerosis: Sensory onset symptoms were associated with both a longer time to and a higher age at Expanded Disability Status Scale (EDSS) 6.0.
Related Papers (5)
Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
Stephen L. Hauser,Amit Bar-Or,Giancarlo Comi,Gavin Giovannoni,Hans Peter Hartung,Bernhard Hemmer,Fred D. Lublin,Xavier Montalban,Kottil Rammohan,Krzysztof Selmaj,A. Traboulsee,Jerry S. Wolinsky,Douglas L. Arnold,Gaelle Klingelschmitt,Donna Masterman,Paulo Fontoura,Shibeshih Belachew,Peter Chin,N. Mairon,Hideki Garren,Ludwig Kappos +20 more
Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis
Xavier Montalban,Stephen L. Hauser,Ludwig Kappos,Douglas L. Arnold,Amit Bar-Or,Giancarlo Comi,Jérôme De Seze,Gavin Giovannoni,Hans-Peter Hartung,Bernhard Hemmer,Fred D. Lublin,Kottil Rammohan,Krzysztof Selmaj,Anthony Traboulsee,Annette Sauter,Donna Masterman,Paulo Fontoura,Shibeshih Belachew,Hideki Garren,N. Mairon,Peter Chin,Jerry S. Wolinsky +21 more