- |||||||||| [VIRTUAL] Comparative Efficacy of Relapsing Multiple Sclerosis Therapies: A Model-Based Meta-Analysis for Annual Relapse Rate () - Aug 16, 2020 - Abstract #MSDC2020MSDC_129;
Results suggested that ponesimod had numerically superior ARR benefits compared to interferon β-1a (subcutaneous), peginterferon β-1a, glatiramer acetate, and dimethyl fumarate (RR range: 0.68–0.94). Ponesimod had similar ARR benefits to S1P receptor modulators ozanimod, fingolimod, cladribine, and daclizumab (RR range: 1.00–1.04).Conclusions Ponesimod reduced ARR in patients with RMS, and was statistically superior as compared with placebo and a range of other DMTs.
- |||||||||| [VIRTUAL] Comparative Efficacy of Relapsing Multiple Sclerosis Therapies: A Longitudinal Model-Based Meta-Analysis for Confirmed Disability Accumulation () - Aug 16, 2020 - Abstract #MSDC2020MSDC_128;
Results favored ponesimod in comparison to placebo (HR: 0.61; 95% CI: 0.44–0.83), glatiramer acetate (0.65; 0.44–0.94), and interferon β-1b (0.51; 0.33–0.77) in delaying 12-week CDA. Ponesimod was estimated to have numerical improvement to S1P receptor modulators fingolimod, ozanimod, laquinimod, as well as teriflunomide, interferon β-1a (intramuscular and subcutaneous), peginterferon β-1a, cladribine, daclizumab, and dimethyl fumarate (HR range: 0.77–0.94).Conclusions Ponesimod was statistically superior compared to placebo and a range of other DMTs suggesting robust efficacy in the treatment of MS.
- |||||||||| Campath (alemtuzumab) / Sanofi, Zinbryta (daclizumab) / Biogen, AbbVie, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Journal: Variable Benefits of Antibody Induction by Kidney Allograft Type. (Pubmed Central) - Aug 6, 2020
While seemingly beneficial for recipients of all kidneys, induction has more robust associations with lower graft failure and acute rejection probability for recipients of ARF kidneys. Given the lack of observed benefit for ECD recipients, induction policies should be carefully considered in these patients.
- |||||||||| Clinical, Reimbursement, Journal, Medicaid: Expenditure, Utilization, and Cost of Specialty Drugs for Multiple Sclerosis in the US Medicaid Population, 2008-2018. (Pubmed Central) - Jul 30, 2020
The specialty drugs considered in our analysis included dimethyl fumarate, fingolimod, teriflunomide, cladribine, siponimod, alemtuzumab, natalizumab, ocrelizumab, daclizumab, glatiramer acetate, peginterferon beta-1a, interferon beta-1a, and interferon beta-1b...The growing utilization and spending trends for specialty MS medications are significant and sizable in the US Medicaid programs. Medicaid cost-containment strategy is warranted to control the economic burden of state budgets across the country.
- |||||||||| Campath (alemtuzumab) / Sanofi, Zinbryta (daclizumab) / Biogen, AbbVie
Clinical, Journal: Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation. (Pubmed Central) - Jul 22, 2020
Of 47 258 recipients, 29.3% received IL-2 receptor antagonist (IL-2RA), 33.3% received anti-thymocyte globulin (ATG), 7.3% received alemtuzumab, and 30.0% received no induction...Only in the ATG group, 7% lower hazard of the composite outcome of mortality and CVE was noted. Induction agents are not associated with incident CVE; although prospective trials are needed to determine a personalized approach to prevention.
- |||||||||| Clinical, Journal: Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant. (Pubmed Central) - Jun 18, 2020
Combinations of each induction (basiliximab, daclizumab, antithymocyte globulin, alemtuzumab, or none) and maintenance (tacrolimus plus sirolimus, mycophenolate mofetil, or azathioprine) therapy were also compared...The induction-maintenance combination with the highest survival was sirolimus plus tacrolimus without induction therapy (median survival, 10.7 years [IQR, 7.3-12.7 years]; aHR, 0.48; 95% CI, 0.31-0.76; P = .002) compared with mycophenolate mofetil plus tacrolimus with induction therapy (median survival, 7.4 years [IQR, 3.9-12.6 years]). Sirolimus plus tacrolimus was associated with improved patient survival after lung transplant compared with mycophenolate mofetil plus tacrolimus; no antibody induction therapy with sirolimus plus tacrolimus was associated with maximal survival.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie
[VIRTUAL] Daily Immunosuppression to Combat Compliance in Adolescent Kidney Transplant (Virtual) - May 29, 2020 - Abstract #ATC2020ATC_988;
Two patients did progress to graft failure; however, the remaining patients demonstrated fewer rejection episodes and a preserved GFR. While medication compliance is multifactorial, daily dosing of immunosuppression can be considered in this patient population.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie
The CD25 antibody RG6292 selectively depletes Tregs while preserving IL-2 signaling and CTL activity for tumor control (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_1560;
P1
RG6292 selectively favors the depletion of CD25 high Tregs over CD25 low activated CTLs, here shown in comparison to ipilimumab and mogamulizumab in human αCD3 activated PBMC, human tumor explants and immunopharmacodynamic studies in tumor bearing (BxPC-3), stem cell humanized mice and cynomolgus monkeys...Earlier immunosuppressant anti-CD25 antibodies (e.g. daclizumab and basiliximab) interfered with the formation of the high affinity IL-2R complex...RG6292 provides a novel therapeutic approach to alleviate a major mechanism of immune suppression in the tumor microenvironment. Clinical testing is currently ongoing to evaluate the safety and tolerability of RG6292 in patients with advanced solid tumors (NCT04158583).
- |||||||||| Review, Journal: The Use of Biologic Agents in the Management of Uveitis. (Pubmed Central) - May 13, 2020
Management includes topical and systemic corticosteroid therapy and conventional immunomodulatory agents, including methotrexate, azathioprine, mycophenolate mofetil and cyclosporin...These include TNF-α inhibitors, such as infliximab, adalimumab and etanercept; interleukin blockers, such as tocilizumab and daclizumab; and other targeted therapies, such as rituximab and abatacept...This comprehensive review aims to construct an updated summary on the existing evidence pertaining to the use of biologic agents in the treatment of uveitis. Methods include a systematic search for studies between 2000 to 2018 using PubMed, EMBASE, Ovid MEDLINE, and Cochrane libraries.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie
Trial completion, Phase classification: New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial (clinicaltrials.gov) - May 5, 2020
P2, N=126, Completed,
Methods include a systematic search for studies between 2000 to 2018 using PubMed, EMBASE, Ovid MEDLINE, and Cochrane libraries. Phase classification: P3 --> P2 | Active, not recruiting --> Completed
- |||||||||| tacrolimus / Generic mfg., sirolimus / Generic mfg., University of Cincinnati, Zinbryta (daclizumab) / Biogen, AbbVie
Clinical, Journal: Steroid-Free Immune Suppression Impairs Glycemic Control in a Healthy Cynomolgus Monkey. (Pubmed Central) - May 1, 2020
Histological evaluation of the pancreas revealed islet hyperplasia, with varying sizes and endocrine cell ratios that differed from normal islet composition, and parenchymal infiltration with adipose tissue. These deleterious effects of IS on glucose control and endocrine components in the native pancreas of a healthy NHP suggest that IS agents commonly utilized for islet transplantation may contribute to failure in islet allograft function in long-term transplant patients.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie, Lemtrada (alemtuzumab) / Sanofi
[VIRTUAL] Association of sarcoidosis and multiple sclerosis: an important lesson in neuroimmunology (ePoster) - Apr 9, 2020 - Abstract #EAN2020EAN_640;
We postulate that the state of mild immuno- suppression, lymphopenia and normal or increased levels of 1,25 OH-vitamin D3 in sarcoidosis is protective against disease activity in MS. This is supported by the low incidence of MS in patients with sarcoidosis, and development of acute sarcoidosis reported in patients with MS following treatment with beta-interferon, alemtuzumab and daclizumab, probably from a shift of immune response and macrophage activity.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie
Clinical, Journal: A case of immune-mediated encephalitis related to daclizumab therapy. (Pubmed Central) - Mar 29, 2020
The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie
Journal: Immune-mediated encephalitis with daclizumab: The final nail. (Pubmed Central) - Mar 29, 2020
We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy. We provide clinical commentary on this edition's case report of immune-mediated encephalitis related to daclizumab therapy.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie
Journal: IL-2 receptors preassemble and signal in the ER/Golgi causing resistance to antiproliferative anti-IL-2Rα therapies. (Pubmed Central) - Mar 29, 2020
Anti-IL-2Rα (daclizumab) therapy targeting cell surface-expressed receptor subunits to inhibit T cell proliferation has only brought limited success in adult T cell leukemia/lymphoma (ATL) and in multiple sclerosis...Confocal microscopy, Förster resonance energy transfer, and imaging fluorescence cross-correlation spectroscopy analysis revealed partial colocalization and molecular association of IL-2 (and IL-15) receptor chains in the ER/Golgi, which became more complete in the plasma membrane, further confirming our hypothesis. Our results define a paradigm of intracellular autocrine signaling and may explain resistance to antagonistic antibody therapies targeting receptors at the cell surface.
- |||||||||| Tecfidera (dimethyl fumarate) / Biogen, Zinbryta (daclizumab) / Biogen, AbbVie, Lemtrada (alemtuzumab) / Sanofi
[VIRTUAL] EXPENDITURE, UTILIZATION, AND PRICE OF SPECIALTY DRUGS FOR MULTIPLE SCLEROSIS IN THE U.S MEDICAID POPULATION 2008 - 2018 () - Mar 8, 2020 - Abstract #ISPOR2020ISPOR_1118;
Specialty drugs included dimethyl fumarate, fingolimod, teriflunomide, alemtuzumab, natalizumab, ocrelizumab, daclizumab, glatiramer acetate, peginterferonb1A, interferonb1A , and interferon b1B...Intermarket and interbrand competition among the MS specialty drugs were also observed. Medicaid policymakers should investigate new ways to contain further spikes in prescription prices in order to control budget burden on states and government.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie, Rituxan (rituximab) / Roche, Biogen, Zenyaku Kogyo, Lemtrada (alemtuzumab) / Sanofi
Review, Journal: Established and Emerging Immunological Complications of Biological Therapeutics in Multiple Sclerosis. (Pubmed Central) - Mar 4, 2020
Here we review established and emerging risks associated with multiple sclerosis biologic agents, with an emphasis on their immunological adverse effects. We also discuss the specific challenges that multiple sclerosis biologics pose to drug safety systems, and the potential for improvements in safety frameworks.
- |||||||||| Humira (adalimumab) / Eisai, AbbVie, Zinbryta (daclizumab) / Biogen, AbbVie
[VIRTUAL] Immunotherapy and psychosis: it there a risk? (All Screens in Poster Area) - Feb 20, 2020 - Abstract #EPA2020EPA_1091;
The available literature reports a low prevalence of psychotic symptoms associated with the use of monoclonal antibodies but it highlights the importance in knowing the immune mechanisms involved in psychotic disorders. Greater research is needed to correctly assess that risk.
- |||||||||| Campath (alemtuzumab) / Sanofi, tacrolimus / Generic mfg., Zinbryta (daclizumab) / Biogen, AbbVie
Clinical, Journal: Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (the 3C Study) - results of a randomized controlled clinical trial. (Pubmed Central) - Dec 21, 2019
P2/3
The 3C Study was a pragmatic randomized controlled trial of sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6 months posttransplantation...Biopsy-proven acute rejection (29 [14.7%]) vs 6 [3.0%]; p<0.001) and serious infections (defined as opportunistic infections or those requiring hospitalisation; 95 [48.2%] versus 70 [35.5%]; p=0.008) were more common among participants allocated sirolimus. Compared with tacrolimus-based therapy, sirolimus-based maintenance therapy did not improve transplant function at 18 months after conversion and was associated with significant hazards of rejection and infection.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Trial completion, Trial completion date: Phase I/II Thymus Transplantation With Immunosuppression #950 (clinicaltrials.gov) - Dec 2, 2019
P1/2, N=28, Completed,
In summary, it appears that more effective AMR prevention/treatment strategies are warranted. Active, not recruiting --> Completed | Trial completion date: Jun 2027 --> Jun 2019
- |||||||||| Tecfidera (dimethyl fumarate) / Biogen, Zinbryta (daclizumab) / Biogen, AbbVie, Lemtrada (alemtuzumab) / Sanofi
Data-mining for Predicting Therapeutic Response in MS (Grand Ballroom, Convention Center) - Dec 1, 2019 - Abstract #ACTRIMSForum2020ACTRIMS_FORUM_25;
The age at treatment initiation, together with dichotomizationof MS drugs into high- (ocrelizumab, mitoxantrone, alemtuzumab, daclizumab andnatalizumab) and low-efficacy (fingolimod, dimethyl fumarate, interferon-betapreparations, teriflunamide and glatiramer acetate) based on the age-adjustedlinear regression model residuals explained 68% of variance of inhibition ofdisability progression (R2 = 0.6757, p = 6.39 e-09)...Patients older than54 years may still benefit from current drugs if they experience MS relapses orhave contrast-enhancing lesions on brain/spinal cord MRI. However, therisk/benefit ratio of treating elderly MS patients without evidence of lesionalactivity with current MS drugs may be decidedly unfavorable.
- |||||||||| Campath (alemtuzumab) / Sanofi, Zinbryta (daclizumab) / Biogen, AbbVie
Journal: Induction Type and Outcomes in HLA-DR Mismatch Kidney Transplantation. (Pubmed Central) - Nov 27, 2019
However, therisk/benefit ratio of treating elderly MS patients without evidence of lesionalactivity with current MS drugs may be decidedly unfavorable. Our study found a patient survival benefit associated with the use of perioperative induction with depleting when compared to non-depleting antibody in KTRs with 2 HLA-DR mismatches and maintained on a calcineurin inhibitor/mycophenolic acid regimen.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie
Journal: Blocking HIF signaling via novel inhibitors of CA9 and APE1/Ref-1 dramatically affects pancreatic cancer cell survival. (Pubmed Central) - Nov 14, 2019
Our studies evaluate PDAC hypoxia responses and APE1/Ref-1 redox signaling contributions to HIF-1α-mediated CA9 transcription...Dual-targeting of APE1/Ref-1 and CA9 in 3D spheroids demonstrated that this combination effectively kills PDAC tumor cells displaying drastically different levels of CA9. New APE1/Ref-1 and CA9 inhibitors were significantly more potent alone and in combination, highlighting the potential of combination therapy targeting the APE1-Ref-1 signaling axis with significant clinical potential.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie
Characteristics of Malignancy in Kidney Transplant Recipients at the Keck Hospital of USC in Year 2006 Through 2009 Compared to Year 2000 Through 2004 (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3490;
Duration until the time of cancer diagnosis after transplant seems shortened considerably; median and mean time, 4 and 6.9 years in group 1 vs. 2.4 and 2.7 years in group 2, respectively. Conclusion In kidney transplant recipients who received a kidney transplant in 2006-2009, incidence of cancer seems increased during 10 year follow-up and duration until the time of cancer diagnosis seems shortened, compared to those in 2000 through 2004, in the patient population studied.
- |||||||||| Clinical, Review, Journal: Cancer Risk in Patients with Multiple Sclerosis: Potential Impact of Disease-Modifying Drugs. (Pubmed Central) - Oct 8, 2019
Because of their action on the immune system, and due to a lack of available long-term data, a special warning of the potential risk of cancer accompanies the use of recent IS such as cladribine, fingolimod, natalizumab or alemtuzumab...For fingolimod, natalizumab, alemtuzumab, dimethyl fumarate, teriflunomide, daclizumab and ocrelizumab, risk management plans outlined by regulatory agencies are mandatory...We review the current evidence behind the increased risk of malignancy in MS patients receiving DMTs, and provide an overview of the DMTs that are currently in use and those in clinical trials. The known risks and benefits of these therapies will be considered.
- |||||||||| Tecfidera (dimethyl fumarate) / Biogen, Zinbryta (daclizumab) / Biogen, AbbVie, Rituxan (rituximab) / Roche, Biogen
Clinical, Journal: Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US. (Pubmed Central) - Sep 6, 2019
Newer DMTs are often used in pediatric MS, and have similar short-term safety, tolerability, and side effect profiles as in adults. These findings may help inform pediatric MS management.
- |||||||||| A real-world study of Alemtuzumab in a cohort of Italian patients (Poster Exhibition) - Aug 28, 2019 - Abstract #ECTRIMS2019ECTRIMS_1043;
Alemtuzumab decreases ARR independent of previous therapy, including patients with disease activity during Natalizumab. Relapses between treatment courses are associated with higher disease activity during follow-up.
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