Therapeutic Applications of Monoclonal Antibodies in Multiple Sclerosis

2019 ◽  
Author(s):  
Hadis Musavi ◽  
Hemen Moradi-Sardareh ◽  
Mohammad Javad Mousavi ◽  
Saeed Aslani ◽  
Amirhooman Asadi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Late Phase ◽  
Antibody Therapy ◽  
Structural Features ◽  
Chronic Inflammatory Disease ◽  
Phase Iii ◽  
Complement Dependent Cytotoxicity ◽  
Phase Iii Trials

Despite the various therapies available, the use of monoclonal antibodies is a highly specific approach that has only recently been of interest to researchers. The properties of antibodies have led to their use in the treatment of various diseases, including cancer, Alzheimer's disease, diabetes and multiple sclerosis (MS). MS, a chronic inflammatory disease, occurs commonly in young adults. The disease is one of the attractive options for monoclonal antibody therapy because it has no definitive drug for its treatment. Antibodies, by targeting different molecules, have different mechanisms to improve the disease. Treatment with monoclonal antibody has culminated in a clear divergence in paradigm and concentration in MS therapeutics. Application of monoclonal antibody in early inflammatory phases can inhibit or postpone the disability in MS subjects. Ocrelizumab and daclizumab are currently under investigation by late phase III trials, and some other monoclonal antibodies are in the early stages of clinical trials. Monoclonal antibodies are of special structural features (including chimeric, humanized, or fully humanized) as well as specific targets (such as stimulation of signal transduction by binding to receptors, blocking interactions, antibody-dependent cell cytotoxicity, complement-dependent cytotoxicity), thus providing various mechanisms of actions during MS therapy. In the present paper, we reviewed different monoclonal antibodies used in MS, their mechanism of action and theirs target molecules.

scholarly journals Pharmacotherapy Options for Multiple Sclerosis: Focus on Natalizumab

2010 ◽  
Vol 2 ◽  
pp. CMT.S2043 ◽  
Author(s):  
Martin Stangel ◽  
Bernd C. Kieseier
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Safety Management ◽  
Jc Virus ◽  
Unmet Need ◽  
Neurological Impairment ◽  
Phase Iii ◽  
First Line ◽  
Two Phase ◽  
Phase Iii Trials

Multiple sclerosis (MS) is considered an autoimmune disease causing demyelination in the central nervous system (CNS) that subsequently leads to axonal damage and neurological impairment. Currently available first line therapies are based on immunomodulation with beta-interferons or glatirameracetate. However, these treatments are only partially effective, thus, more powerful therapies represent an unmet need in MS. Natalizumab is a monoclonal antibody targeting the α4β1 integrin that has been shown to be crucial in the process of transmigration of immunocompetent cells across the blood-brain-barrier (BBB) into the CNS. Two phase III trials have demonstrated clinical and paraclinical efficacy of natalizumab and recent data suggest that many patients that have failed on a first-line disease modifying drug (DMD) benefit from a treatment with natalizumab. Unfortunately, since the licensing of natalizumab in 2006 there have been 75 cases of progressive multifocal leukoencephalopathy (PML) reported. This rare, but potentially fatal infection of the brain by JC-virus restricts the use of natalizumab. Currently there are attempts to define algorithms based on the identification of risk factors for the development of PML to achieve a better safety management for MS patients treated with this monoclonal antibody.

scholarly journals Efficacy and Safety of Existing and Emerging Monoclonal Antibody Therapies for Multiple Sclerosis

2016 ◽  
Vol 11 (2) ◽  
pp. 96
Author(s):  
Gavin Giovannoni ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Structural Characteristics ◽  
Single Class ◽  
Course Of Disease ◽  
Complement Dependent Cytotoxicity ◽  
Dependent Cell ◽  
Advanced Development ◽  
Target Effects

The introduction of monoclonal antibodies for multiple sclerosis (MS) has provided a molecular targeted approach to modify the course of disease. A major advantage of monoclonal antibodies in the treatment of MS is that they are designed to be specific to their target and have very few off-target effects. Monoclonal antibodies have distinct structural characteristics and different targets, and their various mechanisms of action include cross-linking, blocking interactions, induction of signal transduction via receptor binding, complement-dependent cytotoxicity, and antibody-dependent cell-mediated cytotoxicity. Monoclonal antibodies should not therefore be considered a single class of treatments. Natalizumab and alemtuzumab are highly efficacious treatments approved for treating MS, though they tend to be reserved for patients with more active disease. Other monoclonal antibodies in advanced development include ocrelizumab, ofatumumab, anti-CD25 monoclonal antibody, daclizumab and opicinumab (anti-LINGO-1). Screening and monitoring is required to enable the optimal utilisation of all monoclonal antibodies and the benefit–risk profile of each monoclonal antibody needs to be fully considered before use. At present, patients have variable access to effective MS treatments, and this issue is likely to become even more important to address as new therapies become available.

scholarly journals Recent advances in monoclonal antibody therapy in IBD: practical issues

2019 ◽  
Vol 10 (4) ◽  
pp. 409-416 ◽  
Author(s):  
Aravind Gokul Tamilarasan ◽  
Georgina Cunningham ◽  
Peter M Irving ◽  
Mark A Samaan
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Late Phase ◽  
Antibody Therapy ◽  
Therapeutic Drug ◽  
Clear Understanding ◽  
Treatment Algorithms ◽  
Look Ahead ◽  
Inflammatory Bowel

The advent of monoclonal antibody therapies has revolutionised inflammatory bowel disease (IBD) treatment and delivered great benefits to patients. The optimal use of this class of drugs requires careful management and a clear understanding of their properties. In this review article, we consider how to maximise the benefit of our most novel biological agents, vedolizumab and ustekinumab. For each agent, we consider practical aspects including dose flexibility, evidence for use in combination with a conventional immunomodulator and the potential role of therapeutic drug monitoring. We also address positioning of the various mechanisms and agents in treatment algorithms as well as important aspects of managing patients receiving monoclonal antibodies, such as disease reassessment. Finally, we look ahead to the future of monoclonal antibodies, where not only have biosimilars increased the number of agents available but there are also a range of novel mechanisms currently in late phase clinical trials.

Ziprasidone Mesylate for Injection

2002 ◽  
Vol 37 (12) ◽  
pp. 1307-1317
Author(s):  
Dennis J. Cada ◽  
Terri Levien ◽  
Danial E. Baker
Keyword(s):  
Information Exchange ◽  
Hospital Pharmacy ◽  
Adefovir Dipivoxil ◽  
Late Phase ◽  
Phase Iii ◽  
Bulletin Board ◽  
Target Drug ◽  
Agalsidase Alfa ◽  
Phase Iii Trials ◽  
Drug Utilization Evaluation

Each month, subscribers to The Formulary Monograph Service receive five to six well-documented monographs on drugs that are newly released or are in late Phase III trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly one-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. The monographs are published in printed form and on diskettes that allow customization. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800–322–4349. The November 2002 monograph topics are adefovir dipivoxil, ximelagatran, agalsidase alfa and agalsidase beta, pemetrexed, and emtricitabine. The DUE is on adefovir dipivoxil.

Caspofungin

2001 ◽  
Vol 36 (5) ◽  
pp. 522-533
Author(s):  
Dennis J. Cada ◽  
Terri Levien ◽  
Danial E. Baker
Keyword(s):  
Information Exchange ◽  
Hospital Pharmacy ◽  
Late Phase ◽  
Phase Iii ◽  
Bulletin Board ◽  
Pharmacy And Therapeutics Committee ◽  
Target Drug ◽  
Phase Iii Trials ◽  
Drug Utilization Evaluation ◽  
Formoterol Fumarate

Each month, subscribers to The Formulary® Monograph Service receive five to six researched monographs on drugs that are newly released or are in late Phase III trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly one-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. The monographs are published in printed form and on diskettes that allow customization. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board called The Formulary Information Exchange (The F.I.X). All topics pertinent to clinical pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The May 2001 Formulary monographs are on formoterol fumarate, esomepra-zole, galantamine, valganciclovir, and travoprost. The DUE is on formoterol fumarate.

scholarly journals Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update

2018 ◽  
Vol 19 (12) ◽  
pp. 3924 ◽  
Author(s):  
Hanley Abramson
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Checkpoint Inhibitors ◽  
Proteasome Inhibition ◽  
Phase Iii ◽  
Drug Conjugates ◽  
Fda Approval ◽  
Promising Target ◽  
High Death ◽  
Phase Iii Trials

The past two decades have seen a revolution in multiple myeloma (MM) therapy with the introduction of several small molecules, mostly orally effective, whose mechanisms are based on proteasome inhibition, histone deacetylase (HDAC) blockade, and immunomodulation. Immunotherapeutic approaches to MM treatment using monoclonal antibodies (mAbs), while long in development, began to reap success with the identification of CD38 and SLAMF7 as suitable targets for development, culminating in the 2015 Food and Drug Administration (FDA) approval of daratumumab and elotuzumab, respectively. This review highlights additional mAbs now in the developmental pipeline. Isatuximab, another anti-CD38 mAb, currently is under study in four phase III trials and may offer certain advantages over daratumumab. Several antibody-drug conjugates (ADCs) in the early stages of development are described, including JNJ-63723283, which has attained FDA breakthrough status for MM. Other mAbs described in this review include denosumab, recently approved for myeloma-associated bone loss, and checkpoint inhibitors, although the future status of the latter combined with immunomodulators has been clouded by unacceptably high death rates that caused the FDA to issue clinical holds on several of these trials. Also highlighted are the therapies based on the B Cell Maturation Antigen (BCMA), another very promising target for anti-myeloma development.

scholarly journals Monoclonal Antibody Therapy and Long-term Outcomes in Multiple Sclerosis – The Challenge of Treatment Optimisation

2018 ◽  
Vol 13 (2) ◽  
pp. 78
Author(s):  
Antonio Scalfari ◽  
Paolo A Muraro ◽  
◽  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Antibody Therapy ◽  
Careful Consideration ◽  
Therapeutic Landscape ◽  
Treatment Optimisation ◽  
Frequent Administration ◽  
Therapeutic Opportunity ◽  
The Many ◽  
The Cost

The therapeutic landscape of multiple sclerosis (MS) has been transformed by the advent of several new monoclonal antibody (MAb) therapies that can potentially lead to full stabilisation of detectable disease activity. Natalizumab, alemtuzumab and ocrelizumab are currently licensed MAbs for the treatment of MS. Daclizumab was licensed for the treatment of MS, although it has been recently withdrawn from the market by the manufacturer. Most patients are initially managed with first-line treatments, and, if disease breakthrough occurs, are escalated to a stronger compound, yet the available evidence indicates an early window of therapeutic opportunity for MAbs to exert most of their efficacy. It is important to balance the superior efficacy of MAbs compared with injectable treatments against more serious side effects, although these are well recognised and can be monitored where indicated and treated. In particular, the risk of progressive multifocal leucoencephalopathy with natalizumab can be managed by screening potential patients for the John Cunningham virus. The MAbs also have the benefit of convenience to patients compared with daily or weekly treatments since they are given via less frequent administration. The cost of these treatments, compared with other therapies, may be an important issue in many countries where healthcare budgets are under pressure. The complex decision of choosing the best treatment for an individual should be made jointly between the doctor and the patient after careful consideration of the many factors to be weighed.

scholarly journals Chronic lymphocytic leukemia paradigm continues to be refined: news from the American Society of Hematology 2018 annual meeting

2019 ◽  
Vol 8 (2) ◽  
pp. IJH14
Author(s):  
Stefano Molica
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Standard Of Care ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Phase Iii Trials ◽  
Prospective Phase ◽  
American Society ◽  
Anti Cd20

There were a number of important updates and advances presented at the 2018 Annual American Society of Hematology meeting. With respect to the treatment of chronic lymphocytic leukemia, the American Society of Hematology 2018 was notable for an improved understanding of ibrutinib-based therapies. In fact, three prospective Phase III trials presented at the meeting indicate, in turn, that ibrutinib alone, ibrutinib plus rituximab, or ibrutinib plus obinutuzumab, should be the new standard of care for chronic lymphocytic leukemia. However, additional clinical trials comparing chemo-immunotherapy with ibrutinib alone or in association with an anti-CD20 monoclonal antibody remain a reasonable avenue to complete results of these large studies.

Icodextrin Peritoneal Dialysis Solution

2003 ◽  
Vol 38 (7) ◽  
pp. 669-678
Author(s):  
Dennis J. Cada ◽  
Terri Levien ◽  
Danial E. Baker
Keyword(s):  
Information Exchange ◽  
Hospital Pharmacy ◽  
Late Phase ◽  
Ophthalmic Solution ◽  
Phase Iii ◽  
Bulletin Board ◽  
Target Drug ◽  
Dialysis Solution ◽  
Phase Iii Trials ◽  
Peritoneal Dialysis Solution

Each month, subscribers to The Formulary Monograph Service receive five to six well-documented monographs on drugs that are newly released or are in late Phase III trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly one-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. The monographs are published in printed form and on diskettes that allow customization. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800–322–4349. The June 2003 monograph topics are aprepitant, gemifloxacin, desirudin for injection, gatifloxacin ophthalmic solution, and pegvisomant. The DUE is on aprepitant.

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