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Immunosuppression withdrawal

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https://www.readbyqxmd.com/read/28923623/mycophenolate-mofetil-withdrawal-with-conversion-to-everolimus-to-treat-bk-virus-infection-in-kidney-transplant-recipients
#1
D Wojciechowski, S Chandran, A Webber, R Hirose, F Vincenti
BACKGROUND: BK virus (BKV) is a significant post-transplant infection. Mammalian target of rapamycin inhibitors (mTORis) reduce BKV large T antigen expression in vitro and are associated with lower rates of BKV infection when used as de novo immunosuppression in clinical studies. METHODS: We performed a prospective, single-center, randomized, open label pilot trial to evaluate the impact of mycophenolate mofetil (MMF) withdrawal with conversion to the mTORi everolimus versus a 50% reduction of the MMF dose for the treatment of BKV infection after kidney transplantation...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923615/effective-and-safe-reduction-of-conventional-immunosuppressants-using-everolimus-in-maintenance-kidney-transplant-recipients
#2
K Nanmoku, A Kurosawa, T Kubo, T Shinzato, T Shimizu, T Kimura, T Yagisawa
BACKGROUND: Adverse events due to conventional immunosuppressive therapy decrease both graft and patient survival. We aimed to establish a new protocol using everolimus (EVR) to safely minimize conventional immunosuppressants in maintenance kidney transplant recipients. METHODS: A total of 86 consecutive kidney transplant recipients with no complications were maintained with triple-drug combination therapy (conventional group). In case of complications, the administration of very low-dose tacrolimus (C0: 5...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28905454/management-considerations-in-the-failing-renal-allograft
#3
REVIEW
Tom Lea-Henry, Bobby Chacko
Patients with a failed or failing renal transplant are increasing in number. Graft failure resulting in dialysis re-initiation is not uncommon, yet there are limited data to guide management of these patients. Physician practices vary regarding timing of dialysis initiation and the timing and extent of immunosuppression withdrawal. The risks of immunosuppression withdrawal need to be carefully balanced against the benefits of continuing low-dose therapy. The latter helps minimise the risk of sensitisation and has been proposed to possibly slow the loss of residual renal function; however, the use of common immunosuppressive agents may contribute to cardiovascular disease, malignancy, and infection, the major causes of death following the loss of a renal transplant...
September 14, 2017: Nephrology
https://www.readbyqxmd.com/read/28898290/comparative-effectiveness-and-tolerance-of-immunosuppressive-treatments-for-idiopathic-membranous-nephropathy-a-network-meta-analysis
#4
Song Ren, Ying Wang, Li Xian, Tadashi Toyama, Meg Jardine, Guisen Li, Vlado Perkovic, Daqing Hong
BACKGROUND: Immunosuppressive agents in general are shown to prevent renal progression and all-cause mortality in idiopathic membranous nephropathy (IMN) patients with nephrotic syndrome. However, the efficacy and safety of different immunosuppressive treatments have not been systematic assessed and compared. A network meta-analysis was performed to compare different immunosuppressive treatment in IMN. METHODS: Cochrane library, MEDLINE, EMBASE and trial register system were searched for randomized controlled trials reporting the treatments for IMN to May 3, 2016...
2017: PloS One
https://www.readbyqxmd.com/read/28874419/early-intervention-in-crohn-s-disease-towards-disease-modification-trials
#5
REVIEW
Silvio Danese, Gionata Fiorino, Laurent Peyrin-Biroulet
Crohn's disease (CD) is a chronic progressive destructive inflammatory bowel disease. As in rheumatoid arthritis, there is increasing evidence that early treatment initiation with disease-modifying agents, such as biological drugs, may lead to complete disease control, prevention of disease progression thus protecting against irreversible damage and restoration of normal quality of life. Data from randomised clinical trials with immunosuppressants and biologics suggest that treating patients with a disease duration of <2 years and an absence of complications may significantly reduce the risk for complications and increase time in remission in patients with CD...
September 5, 2017: Gut
https://www.readbyqxmd.com/read/28853699/successful-therapy-with-mycophenolic-acid-in%C3%A2-a-membranous-glomerulonephritis-due-to%C3%A2-kimura-disease%C3%A2
#6
Julien Gaillard, Samuel Rotman, Christophe Girardet, François Spertini
Kimura disease (KD) is a rare inflammatory soft tissue disorder of unknown origin most frequent in Asians, the prevalence of which is growing in Western countries. Painless papules and/or nodules with a predilection for the head and the neck region, lymphadenopathies, parotid gland involvement, eosinophilia, and raised IgE levels are parts of its presentation. Renal involvement with various forms of glomerulonephritis, including membranous nephropathy (MN), can occur and is generally associated with a proteinuria that encompasses nephrotic syndrome...
August 30, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28846737/immunosuppressant-prescription-pattern-and-trend-in-kidney-transplantation-a-multicenter-study-in-korea
#7
Ji-Yeun Chang, Jihyun Yu, Byung Ha Chung, Jaeseok Yang, Sung-Joo Kim, Chan-Duck Kim, Sang-Ho Lee, Jong Soo Lee, Joong Kyung Kim, Cheol Woong Jung, Chang Kwon Oh, Chul Woo Yang
BACKGROUND: The actual prescription pattern of immunosuppressive agents in kidney transplantation is unclear. METHODS: We investigated the pattern and trend of immunosuppressive treatment for kidney transplant patients in South Korea. A total of 636 patients at nine transplant centers were enrolled and followed for one year. We reviewed medical records and evaluated induction therapy, as well as the changing pattern and cause of maintenance therapy. RESULTS: Most patients (n = 621, 97...
2017: PloS One
https://www.readbyqxmd.com/read/28834393/drug-free-long-term-remission-in-severe-behcet-s-disease-following-withdrawal-of-successful-anti-tnf-treatment
#8
Petros P Sfikakis, Aikaterini Arida, Stylianos Panopoulos, Kalliopi Fragiadaki, George Pentazos, Katerina Laskari, Maria Tektonidou, Nikos Markomichelakis
OBJECTIVE: To test the hypothesis that remission of Behcet's disease (BD) with severe vital organ involvement is maintained after withdrawal of successful anti-TNF treatment. METHODS: This single-center, retrospective, longitudinal outcome study focused on consecutive patients, refractory to conventional immunosuppressants, who responded to add-on anti-TNF long-term treatment, which was subsequently discontinued. Endpoint was patients' proportion remaining in complete remission for at least 3 years after anti-TNF withdrawal...
August 22, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28828166/is-early-conversion-to-mtor-inhibitors-represent-a-suitable-choice-in-renal-transplant-recipients-a-systemic-review-of-medium-term-outcomes
#9
REVIEW
J Kumar, I Reccia, T Kusano
BACKGROUND: Immunosuppressive therapies are important parts of renal transplantation. OBJECTIVE: To assess the present literature on the effectiveness of early introduction of mTOR inhibitors with or without calcineurin inhibitors (CNI) in renal transplant recipients in terms of renal functioning and graft survival. METHODS: The current literature was reviewed following PROSPERO approval, assessing the role of immunosuppressive agent, mTOR inhibitors as an alternative to CNI within 6 months of renal transplantation by searching PubMed, EMBASE, Cochrane, Crossref, and Scopus...
2017: International Journal of Organ Transplantation Medicine
https://www.readbyqxmd.com/read/28822993/seropositivity-and-titers-of-anti-smooth-muscle-actin-antibody-are-associated-with-relapse-of-type-1-autoimmune-hepatitis
#10
Taro Shibuki, Taiga Otsuka, Hiroshi Isoda, Norimasa Araki, Yoshihito Kubotsu, Yasunori Kawaguchi, Shunya Nakashita, Wataru Yoshioka, Seiji Kawazoe, Hiroaki Kawasoe, Yasushi Ide, Toshihiko Mizuta, Saga Study Group Of Liver Diseases Sasld
BACKGROUND It is important to avoid relapse in autoimmune hepatitis (AIH) because repeated multiple relapses have been associated with a worse prognosis. However, risk factors for relapse before initiation of treatment are not fully understood. The aim of this study was to find predictive markers for relapse of type 1 AIH. MATERIAL AND METHODS We reviewed the records of 53 patients diagnosed with type 1 AIH based on the revised scoring system proposed by the International Autoimmune Hepatitis Group (IAIHG) between 2009 and 2014 at 4 hospitals belonging to the Saga Study Group of Liver Diseases (SASLD)...
August 20, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28806922/hepatitis-b-reactivation-characterized-by-hbsag-negativity-and-anti-hbsag-antibodies-persistence-in-haematopoietic-stem-cell-transplanted-patient-after-lamivudine-withdrawal
#11
C Cerva, G Maffongelli, V Svicher, R Salpini, L Colagrossi, A Battisti, B Mariotti, R Cerretti, L Cudillo, L Sarmati
BACKGROUND: HBV reactivation is associated with high mortality rates in hematopoietic stem cell transplantation (HSCT) and prophylactic lamivudine (LMV) treatment is suggested to prevent this phenomenon. However, the duration of LMV treatment in HSCT patients is not fully defined and the time of immune recovery is considered the best parameter for a drug to be safely interrupted. In patients undergoing allogeneic HSCT, the time of immune recovery is not easy to define and may take years after transplantation and prolonged LMV treatments, which can lead to drug-resistant viral strains...
August 15, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28805142/intravenous-immunoglobulins-modify-relapsing-membranous-glomerulonephritis-after-kidney-transplantation-a-case-report
#12
Sanne Steyaert, Jo Van Dorpe, Anne Hoorens, Wim Van Biesen, Steven Van Laecke
OBJECTIVES: Recurrence of membranous glomerulonephritis after transplant is common and is an important cause of loss of renal graft. This case supports the effect of immunoglobulins in the treatment of this disease after transplantation. It is the first report in the literature with a follow-up of more than 10 years and because of the sustained effect of the immunoglobulins, it strengthens the idea that this can alter long-term outcome. METHODS: Single case study and search of the literature...
August 14, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28771665/tnf-antagonist-induced-lupus-a-critically-appraised-topic
#13
REVIEW
S E Momen, B Kirkham, J N Barker, C H Smith
TNF antagonist induced lupus is diagnosed upon a temporal relationship of TNF antagonist therapy and the development of four of the 11 American college of rheumatology (ACR) diagnostic criteria for lupus. We critically appraise the literature on TNF antagonist induced lupus, focusing on the diagnostic criteria, dermatological manifestations, management and outcome. Eighty cases of TNF antagonist induced lupus that met the ACR criteria were included and analysed. Infliximab was the most commonly reported agent (58...
August 3, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28765938/rapamycin-inhibits-spermatogenesis-by-changing-the-autophagy-status-through-suppressing-mechanistic-target-of-rapamycin-p70s6-kinase-in-male-rats
#14
Shangjing Liu, Longxian Huang, Yanqing Geng, Junlin He, Xuemei Chen, Hao Xu, Rong Li, Yingxiong Wang, Yubin Ding, Xueqing Liu
Rapamycin (sirolimus) is an antiproliferative drug that has been widely used in the clinic as an immunosuppressant and a potential anticancer agent. Certain reports have indicated that rapamycin may induce male infertility through impairing sperm quality. The present study investigated the mechanism of male infertility caused by rapamycin and examined whether withdrawal of rapamycin could recover the number of sperm in rats. Male Sprague‑Dawley rats (n=100) were divided randomly into 5 groups: 3 rapamycin‑treated groups (2, 4 and 6 mg/kg) and 2 control groups [Blank and dimethyl sulfoxide (DMSO)]...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28729300/rapamycin-is-highly-effective-in-murine-models-of-immune-mediated-bone-marrow-failure
#15
Xingmin Feng, Zenghua Lin, Wanling Sun, Maile K Hollinger, Marie J Desierto, Keyvan Keyvanfar, Daniela Malide, Pawel Muranski, Jichun Chen, Neal S Young
Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28729151/standard-dose-pembrolizumab-in-combination-with-reduced-dose-ipilimumab-for-patients-with-advanced-melanoma-keynote-029-an-open-label-phase-1b-trial
#16
Georgina V Long, Victoria Atkinson, Jonathan S Cebon, Michael B Jameson, Bernie M Fitzharris, Catriona M McNeil, Andrew G Hill, Antoni Ribas, Michael B Atkins, John A Thompson, Wen-Jen Hwu, F Stephen Hodi, Alexander M Menzies, Alexander D Guminski, Richard Kefford, Benjamin Y Kong, Babak Tamjid, Archana Srivastava, Anna J Lomax, Mohammed Islam, Xinxin Shu, Scot Ebbinghaus, Nageatte Ibrahim, Matteo S Carlino
BACKGROUND: Reduced-dose nivolumab in combination with standard-dose ipilimumab improves objective response and progression-free survival compared with standard-dose ipilimumab alone, but increases toxicity. We assessed the safety and anti-tumour activity of standard-dose pembrolizumab in combination with reduced-dose ipilimumab. METHODS: In this open-label, phase 1b trial, we recruited patients from 12 medical centres in Australia, New Zealand, and the USA. Eligible patients were aged at least 18 years, had advanced melanoma, had an Eastern Coooperative Oncology Group performance status of 0 or 1, had measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1...
September 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28675117/peripheral-immune-system-suppression-in-early-abstinent-alcohol-dependent-individuals-links-to-stress-and-cue-related-craving
#17
Helen C Fox, Verica Milivojevic, Gustavo A Angarita, Raymond Stowe, Rajita Sinha
BACKGROUND: Peripheral immune system cytokines may play an integral role in the underlying sensitized stress response and alcohol craving during early alcohol withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. METHODS: A total of 39 early abstinent, treatment-seeking, alcohol-dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days...
July 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28669992/treatment-of-membranous-nephropathy-time-for-a-paradigm-shift
#18
REVIEW
Piero Ruggenenti, Fernando C Fervenza, Giuseppe Remuzzi
In patients with membranous nephropathy, alkylating agents (cyclophosphamide or chlorambucil) alone or in combination with steroids achieve remission of nephrotic syndrome more effectively than conservative treatment or steroids alone, but can cause myelotoxicity, infections, and cancer. Calcineurin inhibitors can improve proteinuria, but are nephrotoxic. Most patients relapse after treatment withdrawal and can become treatment dependent, which increases the risk of nephrotoxicity. The discovery of nephritogenic autoantibodies against podocyte M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain- containing protein 7A (THSD7A) antigens provides a clear pathophysiological rationale for interventions that specifically target B-cell lineages to prevent antibody production and subepithelial deposition...
September 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28656563/cutaneous-graft-versus-host-disease-diagnosis-and-treatment
#19
REVIEW
Karla Strong Rodrigues, Carla Oliveira-Ribeiro, Silvia de Abreu Fiuza Gomes, Robert Knobler
Graft-versus-host disease (GVHD) is an immunological reaction and a frequent complication following allogeneic hematopoietic stem cell transplantation. It is associated with high mortality rates and may have a significant negative impact on the patient's quality of life, particularly in the chronic-stage setting. Many different organs can be involved, which leads to a wide range of clinical manifestations. In this context, dermatologists play a key role by diagnosing and treating GVHD from the outset since cutaneous features are not just the most common but are also usually the presenting sign...
June 27, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28655795/first-in-human-study-of-amg%C3%A2-820-a-monoclonal-anti-colony-stimulating-factor-1-receptor-antibody-in-patients-with-advanced-solid-tumors
#20
Kyriakos P Papadopoulos, Larry Gluck, Lainie P Martin, Anthony J Olszanski, Anthony W Tolcher, Gataree Ngarmchamnanrith, Erik Rasmussen, Benny Amore, Dirk Nagorsen, John S Hill, Joe Stephenson
Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and interleukin-34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820.<br /><br />Experimental Design: Adult patients with relapsed or refractory advanced solid tumors received intravenous AMG 820 0...
June 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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