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Annals of Indian Academy of Neurology Sep 2015The newer immunotherapies for multiple sclerosis (fingolimod, natalizumab, dimethyl fumarate, teriflunomide, alemtuzumab) offer advantages of efficacy or tolerability... (Review)
Review
The newer immunotherapies for multiple sclerosis (fingolimod, natalizumab, dimethyl fumarate, teriflunomide, alemtuzumab) offer advantages of efficacy or tolerability over the injectable therapies of the 1990s. But they also have greater risks. As further treatments emerge (daclizumab and ocrelizumab are likely to be licensed in the next two years), the physician needs to be able to place them within a complex landscape of drugs and a specific treatment strategy, which may be an "escalation" or "induction" approach. Whilst on treatment, neurologist and patient need to be vigilant to signs of disease breakthrough or adverse effects.
PubMed: 26538846
DOI: 10.4103/0972-2327.164824 -
The American Journal of Managed Care Nov 2013Disease-modifying therapies (DMTs), known to actively reduce relapses and delay disability progression, have been used for the treatment of relapsing-remitting multiple... (Review)
Review
Disease-modifying therapies (DMTs), known to actively reduce relapses and delay disability progression, have been used for the treatment of relapsing-remitting multiple sclerosis (RRMS) for over a decade. These well-known therapies include intramuscular (IM) interferon (IFN) beta-1a (Avonex), subcutaneous (SC) IFN beta-1a (Rebif), SC IFN beta- 1b (Betaseron; Extavia), and SC glatiramer acetate (Copaxone). These first-line therapies have shown only partial benefits for controlling multiple sclerosis (MS) disease activity and are often associated with inadequate patient adherence. Low patient adherence to therapy may be related to the mode of administration or to the side effects associated with treatment. The intravenous DMT natalizumab (Tysabri; dosed monthly) provides high therapeutic efficacy and good compliance but is considered a second-line intervention because of the associated increased risk for progressive multifocal leukoencephalopathy. In 2010, fingolimod (Gilenya), the first oral DMT, was approved by the US Food and Drug Administration (FDA) for the treatment of MS. Recently, 2 new oral DMTs received FDA approval for the treatment of RRMS: teriflunomide (Aubagio) and dimethyl fumarate (Tecfidera). In addition, oral laquinimod, several monoclonal antibodies (eg, alemtuzumab, daclizumab, and ocrelizumab), and other agents have shown preliminary beneficial results in relapsing MS in phase 3 clinical trials. These new and emerging DMTs may provide a more efficacious individualized therapeutic approach, more favorable methods of administration (eg, oral administration), and/or a lower frequency of infusions (eg, annually, 3-5 daily infusions over a year for alemtuzumab) that may improve patient adherence and clinical outcomes.
Topics: Administration, Oral; Alemtuzumab; Antibodies, Monoclonal, Humanized; Clinical Trials, Phase III as Topic; Crotonates; Daclizumab; Drug Approval; Female; Fingolimod Hydrochloride; Forecasting; Humans; Hydroxybutyrates; Immunoglobulin G; Injections, Intramuscular; Injections, Subcutaneous; Male; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Nitriles; Patient Safety; Prognosis; Propylene Glycols; Severity of Illness Index; Sphingosine; Toluidines; Treatment Outcome
PubMed: 24494635
DOI: No ID Found -
Annals of Medicine Aug 2017Antibody induction therapy aims at preventing acute cellular rejection by reducing T-cell proliferation and activation. We evaluated the efficacy and side effects of two... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antibody induction therapy aims at preventing acute cellular rejection by reducing T-cell proliferation and activation. We evaluated the efficacy and side effects of two anti-interleukin-2 receptor antibodies (IL2RAs), basiliximab and daclizumab, for prevention of liver transplant rejection in adult patients.
METHODS
Randomized controlled trials (RCTs) on basiliximab or daclizumab were identified by searching multiple databases and reference lists published up to July, 2015. Endpoints included acute rejection events and mortality rates. Risk ratio (RR) and 95% confidence interval (CI) were calculated and pooled for a meta-analysis.
RESULTS
Patients treated with IL2RA-based therapy were less likely to suffer acute rejection compared to control group (steroid or steroid-free). Patients in all groups had similar mortality rate. In the subgroup analysis, basiliximab and daclizumab-based therapies did not reduced acute rejection rate. No significant difference was found in mortality rate between both types of IL-2RA treatment groups and control groups. In the subgroup analysis regarding experimental design, no significant difference in the acute rejection and mortality rates were found between "steroid plus IL2RA versus steroid" and "IL2RA versus steroid" groups.
CONCLUSION
IL2RA-based induction therapy reduces rate of acute rejection events but does not reduce mortality. However, optimal regimen relating to IL2RA-based induction therapy remains undetermined. KEY MESSAGES IL2RA-based induction therapy was effective in reduction of acute rejection events but it did not reduce mortality rate. Basiliximab-based induction therapy might be more effective than daclizumab-based induction therapy in reduction of acute rejection. No significant difference in acute rejection and mortality rate was found between types of IL2RAs or IL2RA-steroid combined therapy.
Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Basiliximab; Daclizumab; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Interleukin-2; Liver Transplantation; Male; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Treatment Outcome
PubMed: 27813419
DOI: 10.1080/07853890.2016.1257862 -
Transplant International : Official... Jan 2009The goal of steroid minimization trials has been to minimize or eliminate steroid-related side-effects while simultaneously not increasing the rate of acute rejection... (Review)
Review
The goal of steroid minimization trials has been to minimize or eliminate steroid-related side-effects while simultaneously not increasing the rate of acute rejection (AR) and chronic graft loss. Early trials of late steroid withdrawal (> or =3 months post-transplant) were associated with significantly increased AR rates and late graft loss. More recent trials of rapid discontinuation of prednisone (RDP) (< or =7 days post-transplant) have been associated with little or no increase in AR rates and no difference in graft survival (versus maintenance prednisone). Of note, induction therapy appears to be important for success; however, it is not clear if any single maintenance protocol is superior. Intermediate-term follow-up (5-7 years) is now available for some randomized and nonrandomized trials; graft survival and renal function remain excellent. Most of these trials have been done in low immunologic risk recipients, but there are reports of success of RDP in children, black recipients, sensitized recipients, recipients with potentially recurring disease, and kidney-pancreas recipients. Of critical importance, steroid-related side-effects have been minimized. Steroid minimization protocols can clearly be recommended for low-risk patients; additional trials are necessary for those at higher risk. Additional research is also necessary on integrating calcineurin inhibitor minimization with steroid minimization.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child; Clinical Trials as Topic; Daclizumab; Graft Rejection; Graft Survival; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Transplantation; Pancreas Transplantation; Prednisone; Recurrence; Steroids; Substance Withdrawal Syndrome; Time Factors
PubMed: 18662366
DOI: 10.1111/j.1432-2277.2008.00728.x -
Clinical and Experimental Immunology Mar 2014Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and... (Review)
Review
Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short- and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing-remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future.
Topics: Antibodies, Monoclonal; Cell Migration Inhibition; Humans; Immunologic Factors; Immunotherapy; Integrin alpha4; Lymphocytes; Multiple Sclerosis; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Receptors, Lysosphingolipid
PubMed: 24032475
DOI: 10.1111/cei.12195 -
Drug Design, Development and Therapy 2013Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It can present in several forms, with the relapsing-remitting... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It can present in several forms, with the relapsing-remitting pattern being the most common. Since the approval of the first disease-modifying therapy and the initiation of appropriate treatments from the early stages of the disease, there seem to be positive impacts on the long-term outcomes and disability associated with MS. Currently, there are ten approved drugs for the treatment of MS, and several more are in various stages of development. These medications each have their unique profile in terms of efficacy, dose, routes of administration, tolerability, and adverse effects. Daclizumab is a humanized monoclonal antibody that is being explored for the treatment of MS. It is currently approved for use in allograft renal transplantation. Given its modulatory effects on the immune system, daclizumab's potential for use in MS was tested in extensive Phase II trials. With continued demonstration of its efficacy, it is currently in a Phase III trial for relapsing-remitting MS. While daclizumab has demonstrated beneficial effects in controlling disease activity in MS, there were also some safety and tolerability concerns that were raised. Further information from the ongoing Phase III trial, and from open-label studies, will shed light on the benefit and risk profile of this drug and its potential for use in MS.
Topics: Antibodies, Monoclonal, Humanized; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Daclizumab; Drug Approval; Drug Design; Humans; Immunoglobulin G; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting
PubMed: 24143075
DOI: 10.2147/DDDT.S27766 -
Neurotherapeutics : the Journal of the... Oct 2017Patient-reported outcomes (PROs) are playing an increasing role in multiple sclerosis (MS) research and practice, and are essential for understanding the effects that MS... (Review)
Review
Patient-reported outcomes (PROs) are playing an increasing role in multiple sclerosis (MS) research and practice, and are essential for understanding the effects that MS and MS treatments have on patients' lives. PROs are captured directly from patients and include symptoms, function, health status, and health-related quality of life. In this article, we review different categories (e.g., generic, targeted, preference-based) of PRO measures and considerations in selecting a measure. The PROs included in MS clinical research have evolved over time, as have the measures used to assess them. We describe findings from recent MS clinical trials that included PROs when evaluating Food and Drug Administration-approved disease-modifying therapies (e.g., daclizumab, teriflunomide). Variation in the measures used in these trials makes it difficult to draw any conclusions from the data. We therefore suggest a standardized approach to PRO assessment in MS research and describe 2 generic, National Institutes of Health-supported measurement systems [Neuro-QoL and the Patient-Reported Outcomes Measurement Information System (PROMIS)] that would facilitate such an approach. The use of PROs in MS care and research is expanding beyond clinical trials, as is demonstrated by examples from comparative effectiveness and other patient-centered research. The importance of PRO assessment is expected to continue to grow in the future.
Topics: Clinical Trials as Topic; Endpoint Determination; Humans; Multiple Sclerosis; Patient Reported Outcome Measures; Quality of Life; Treatment Outcome
PubMed: 28913785
DOI: 10.1007/s13311-017-0571-6 -
Archivum Immunologiae Et Therapiae... Apr 2012Antibodies have been the cornerstone of treatment of acquired aplastic anemia for more than 25 years. Treatment with antithymocyte globulin (ATG) is considered pivotal... (Review)
Review
Antibodies have been the cornerstone of treatment of acquired aplastic anemia for more than 25 years. Treatment with antithymocyte globulin (ATG) is considered pivotal and the addition of cyclosporine improves the overall response rate. This antibody is heterogeneous and horse ATG is apparently more effective than rabbit ATG. Several issues remain unsolved in relation to the combination of ATG and cyclosporine: cost, toxicity and late clonal disorders. In recent years, alternative immunosuppressive therapy has been proposed and new antibodies have emerged: porcine ATG, alemtuzumab, daclizumab, and rituximab. Experience with these antibodies is limited to a few studies with alemtuzumab being the most promising, but the results are interesting and provocative. More studies are needed to find the perfect antibody.
Topics: Alemtuzumab; Anemia, Aplastic; Animals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antilymphocyte Serum; Clinical Trials as Topic; Cyclosporine; Daclizumab; Drug Interactions; Horses; Humans; Immunoglobulin G; Immunosuppressive Agents; Immunotherapy; Rabbits; Rituximab; Swine
PubMed: 22307362
DOI: 10.1007/s00005-012-0164-3 -
Revista de Neurologia Apr 2018
Topics: Daclizumab; Humans; Immunosuppressive Agents; Interferon-beta; Multiple Sclerosis
PubMed: 29645067
DOI: No ID Found -
Ophthalmology and Therapy Dec 2021Scleritis refers to a wide spectrum of ocular conditions ranging from mild to sight-threatening scleral inflammation that may compromise visual function and threaten the... (Review)
Review
Scleritis refers to a wide spectrum of ocular conditions ranging from mild to sight-threatening scleral inflammation that may compromise visual function and threaten the anatomical integrity of the ocular globe. Most aggressive forms like necrotizing or posterior scleritis are often difficult-to-treat cases, refractory to conventional treatment. The association with systemic diseases, namely rheumatoid arthritis, Sjögren syndrome, granulomatosis with polyangiitis, and relapsing polychondritis, may have prognostic implications as well. A better understanding of the pathogenesis of ocular inflammatory diseases have paved the way to more effective and targeted treatment approaches. In this regard, a growing body of evidence supports the potential role of biologic agents in the management of non-infectious scleral inflammation, either idiopathic or in a background of immune-mediated systemic disorders. Biologic agents such as anti-tumor necrosis factor agents, interleukin-1 and interleukin-6 inhibitors as well as CD20 blockade have displayed promising results. More specifically, several studies have reported their ability to control scleral inflammation, reduce the overall scleritis relapses, and allow a glucocorticoid-sparing effect while being generally well tolerated. Anecdotal reports have also been described with other biologic agents including abatacept, ustekinumab, daclizumab, and alemtuzumab as well as targeted small molecules such as tofacitinib. Further studies are warranted to fully elucidate the role of biologic agents in non-infectious scleritis and investigate specific areas with the aim to administer treatments in the context of personalized medicine. This review summarizes the available data regarding clinical trials, small pilot studies, and real-life experience of the last two decades reporting the use of biologic agents in the management of non-infectious scleritis.
PubMed: 34476773
DOI: 10.1007/s40123-021-00393-8