Treatment of Pemphigus and Pemphigoid with Immunosuppressive Agents

SummaryInhibitor development is a rare but serious event in hemophilia B patients. Management is hampered by the frequent occurrence of allergic reactions to factor IX, low success rates of current inhibitor elimination protocols and the risk of development of nephrotic syndrome. Single cases of immune tolerance induction (ITI) including immunosuppressive agents like mycophenolat mofetil (MMF) or rituximab have been reported. We present a case of successful inhibitor elimination with a combined immune-modulating therapy and high-dose factor IX (FIX). This boy had developed a FIX inhibitor at the age of 5 years and had a history of allergic reactions to FIX and to FEIBA→. Under on-demand treatment with recombinant activated FVII the inhibitor became undetectable but the boy suffered from multiple joint and muscle bleeds. At the age of 11.5 years ITI was attempted with a combination of rituximab, MMF, dexamethasone, intravenous immunoglobulins and high-dose FIX. The inhibitor did not reappear and FIX half-life normalized. No allergic reaction, no signs of nephrotic syndrome and no serious infections were observed.

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Overview of Biological Therapy in Ulcerative Colitis: Current and Future Directions

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.242.bezz ◽

2015 ◽

Vol 24 (2) ◽

pp. 203-213 ◽

Cited By ~ 9

Author(s):

Federica Furfaro ◽

Cristina Bezzio ◽

Sandro Ardizzone ◽

Alessandro Massari ◽

Roberto De Franchis ◽

...

Keyword(s):

Ulcerative Colitis ◽

Immunosuppressive Agents ◽

Mucosal Healing ◽

Aminosalicylic Acid ◽

Proinflammatory Mediators ◽

Experimental Drugs ◽

New Treatments ◽

Aggressive Clinical Course ◽

Near Future

The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly.To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies.The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse.

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New therapeutic approaches for polymyositis and dermatomyositis

Orvosi Hetilap ◽

10.1556/oh.2011.29176 ◽

2011 ◽

Vol 152 (39) ◽

pp. 1552-1559 ◽

Cited By ~ 2

Author(s):

Katalin Dankó ◽

Melinda Vincze

Keyword(s):

Immunosuppressive Agents ◽

Inflammatory Myopathy ◽

Proximal Muscle ◽

Therapeutic Approaches ◽

First Line ◽

New Therapeutic Approaches ◽

Remission Period ◽

Immune Mediated ◽

Systemic Manifestations ◽

Line Of Therapy

Inflammatory myopathies are chronic, immune-mediated diseases characterized with progressive proximal muscle weakness. They encompass a variety of syndromes with protean manifestations. The aims of therapy are to increase muscle strength, prevent the development of contractures, and to manage the systemic manifestations of the disease. This is a complex treatment which requires routine and wide knowledge. The most important task is to recognize the disease and guide the patient to immunologic center. Although the first line of therapy continues to include corticosteroids, there are a multitude of agents available for treating patients with myositis. There are several different immunosuppressive agents which may be applied alone or in combination with each other, as well as an increasing number of novel and exciting biologic agents targeting molecules participating in the pathogenesis of inflammatory myopathy. Physiotherapy and rehabilitation in the remission period may significantly improve the functional outcome of patients with these disorders. Orv. Hetil., 2011, 152, 1552–1559.

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Faculty Opinions recommendation of Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions: cohort study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727378100.793530802 ◽

2017 ◽

Author(s):

Joel Gelfand ◽

Megan Noe

Keyword(s):

Cohort Study ◽

Pregnant Women ◽

Immunosuppressive Agents ◽

Inflammatory Conditions ◽

Serious Infections

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Novel Therapeutic Approaches and Targets for Treatment of Chronic Urticaria: New Insights and Promising Targets for a Challenging Disease

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200630140137 ◽

2020 ◽

Vol 22 (1) ◽

pp. 32-45

Author(s):

Emanuela Martina ◽

Federico Diotallevi ◽

Tommaso Bianchelli ◽

Matteo Paolinelli ◽

Annamaria Offidani

Keyword(s):

English Language ◽

Life Experience ◽

Case Reports ◽

Immunosuppressive Agents ◽

Real Life ◽

Chronic Spontaneous Urticaria ◽

New Targets ◽

Current State ◽

Pubmed Database ◽

Novel Drugs

Background: Chronic Spontaneous Urticaria (CSU) is a disease characterized by the onset of wheals and/or angioedema over 6 weeks. The pathophysiology for CSU is very complex, involving mast cells and basophils with a multitude of inflammatory mediators. For many years the treatment of CSU has been based on the use of antihistamines, steroids and immunosuppressive agents with inconstant and frustrating results. The introduction of omalizumab, the only licensed biologic for antihistamine- refractory CSU, has changed the management of the disease. Objective: The aim of this article is to review the current state of the art of CSU, the real-life experience with omalizumab and the promising drugs that are under development. Methods:: An electronic search was performed to identify studies, case reports, guidelines and reviews focused on the new targets for the treatment of chronic spontaneous urticaria, both approved or under investigation. The search was limited to articles published in peer-reviewed journals in the English Language in the PubMed database and trials registered in Clinicaltrials.gov. Results:: Since the advent of omalizumab, the search for new therapies for chronic spontaneous urticaria has had a new impulse. Anti-IgE drugs will probably still be the cornerstone of therapy, but new targets may prove effective in syndromic urticaria or refractory cases. Conclusion:: Although omalizumab has been a breakthrough in the treatment of CSU, many patients do not completely get benefit and even require more effective treatments. Novel drugs are under investigation with promising results.

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Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190118113201 ◽

2019 ◽

Vol 19 (4) ◽

pp. 473-486 ◽

Cited By ~ 1

Author(s):

Katarzyna Bednarska-Szczepaniak ◽

Damian Krzyżanowski ◽

Magdalena Klink ◽

Marek Nowak

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Biology ◽

Immune Cell ◽

Immunosuppressive Agents ◽

Cell Activity ◽

Ovarian Cancer Cells ◽

Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

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Impact of immunosuppressive agents on clinical manifestations and outcome of Staphylococcus aureus bloodstream infection – A propensity score matched analysis in two large, prospectively evaluated cohorts

Clinical Infectious Diseases ◽

10.1093/cid/ciab385 ◽

2021 ◽

Author(s):

Johannes Camp ◽

Lina Glaubitz ◽

Tim Filla ◽

Achim J Kaasch ◽

Frieder Fuchs ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Propensity Score ◽

Bloodstream Infection ◽

Cox Regression ◽

Immunosuppressive Agents ◽

Late Complications ◽

Competing Risk ◽

Immunosuppressed Patients ◽

Staphylococcus Aureus Bloodstream Infection ◽

Baseline Characteristics

Abstract Background Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. Methods Data from two large prospective, international, multicenter cohort studies (INSTINCT and ISAC) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score (PS) matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroids [CSMT] and immunosuppressive agents other than steroids [IMOTS]). Results Of 3,188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 non-immunosuppressed patients. After PS matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the two groups (death during follow-up: 105/309 (33.9 %) immunosuppressed patients vs. 94/309 (30.4 %) non-immunosuppressed, hazard ratio 1.20 (95% CI 0.84–1.71). Competing risk analysis showed a cause-specific hazard ratio (CSHR) of 1.81 (95% CI 0.85–3.87) for SAB-related late-complications in patients receiving immunosuppressive agents. CSHR was higher in patients taking IMOTS (3.69; 95% CI 1.41–9.68). Conclusions Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTs warrants further investigations.

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Preimplantation genetic testing for aneuploidy in uterus transplant patients

Therapeutic Advances in Reproductive Health ◽

10.1177/26334941211009848 ◽

2021 ◽

Vol 15 ◽

pp. 263349412110098

Author(s):

Rhea Chattopadhyay ◽

Elliott Richards ◽

Valerie Libby ◽

Rebecca Flyckt

Keyword(s):

Genetic Testing ◽

In Vitro Fertilization ◽

Immunosuppressive Agents ◽

Live Birth Rate ◽

Preimplantation Genetic Testing ◽

Vitro Fertilization ◽

Uterus Transplantation ◽

Advantages And Disadvantages ◽

Dilation And Curettage

Uterus transplantation is an emerging treatment for uterine factor infertility. In vitro fertilization with cryopreservation of embryos prior is required before a patient can be listed for transplant. Whether or not to perform universal preimplantation genetic testing for aneuploidy should be addressed by centers considering a uterus transplant program. The advantages and disadvantages of preimplantation genetic testing for aneuploidy in this unique population are presented. The available literature is reviewed to determine the utility of preimplantation genetic testing for aneuploidy in uterus transplantation protocols. Theoretical benefits of preimplantation genetic testing for aneuploidy include decreased time to pregnancy in a population that benefits from minimization of exposure to immunosuppressive agents and decreased chance of spontaneous abortion requiring a dilation and curettage. Drawbacks include increased cost per in vitro fertilization cycle, increased number of required in vitro fertilization cycles to achieve a suitable number of embryos prior to listing for transplant, and a questionable benefit to live birth rate in younger patients. Thoughtful consideration of whether or not to use preimplantation genetic testing for aneuploidy is necessary in uterus transplant trials. Age is likely a primary factor that can be useful in determining which uterus transplant recipients benefit from preimplantation genetic testing for aneuploidy.

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