BioDrugs (BIODRUGS)

Publications in this journal

• Article: Alpha-1 Antitrypsin Deficiency: New Developments in Augmentation and Other Therapies.

  Alice M Turner
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  ABSTRACT: Alpha 1 antitrypsin deficiency (AATD) is a rare cause of chronic obstructive pulmonary disease. The lung disease is thought to be caused primarily by a lack of effective protection against the harmful effects of neutrophil elastase due to the low AAT levels in the lung. Patients may also develop liver disease due to polymerisation of AAT within hepatocytes. Consequently there has been much research over the years into AAT augmentation therapy in patients with lung disease, initially intravenously, and more recently in inhaled forms. This review article will discuss the role of augmentation therapy in AATD and the current status of recombinant AAT. The potential for other therapeutic strategies, such as blocking polymer formation, enhancing autophagy, gene therapy and stem cell-based treatment, will also be discussed more briefly.
  BioDrugs 06/2013;
• Article: Immunomodulators in Inflammatory Bowel Disease: An Emerging Role for Biologic Agents.

  Roslyn Kemp, Elliott Dunn, Michael Schultz
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  ABSTRACT: Crohn's disease and ulcerative colitis, collectively referred to as inflammatory bowel diseases (IBD), are the result of an aberrant immune response to ubiquitous antigens in a genetically susceptible host. In the past, treatment has focused on immunosuppression with the aim of achieving symptom-free remission. Over the last two decades, with a better understanding of the underlying pathomechanisms and an increased knowledge of the natural disease course, mucosal healing (the endoscopic absence of visible inflammation) has become the target of therapy. Anti-tumor necrosis factor (TNF)-α therapy was introduced in the late 1990s and, for the first time, targeted and effective medication became available. However, these medications are not without significant side effects, and long-term efficacy is only achieved in about one third of patients. Alongside anti-TNF-α agents, a variety of other drugs targeting different aspects of the immune system will become available over the next few years. This review aims to provide a brief summary of immunologic pathways involved in IBD and shows where current and new drugs fit into these pathways.
  BioDrugs 06/2013;
• Article: The Arrival of JAK Inhibitors: Advancing the Treatment of Immune and Hematologic Disorders.

  Yasuko Furumoto, Massimo Gadina
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  ABSTRACT: Altered production of cytokines can result in pathologies ranging from autoimmune diseases to malignancies. The Janus kinase family is a small group of receptor-associated signaling molecules that is essential to the signal cascade originating from type I and type II cytokine receptors. Inhibition of tyrosine kinase enzymatic activity using small molecules has recently become a powerful tool for treatment of several malignancies. Twenty years after the discovery of these enzymes, two inhibitors for this class of kinases have been approved for clinical use and others are currently in the final stage of development. Here we review the principles of cytokines signaling, summarize our current knowledge of the approved inhibitors, and briefly introduce some of the inhibitors that are currently under development.
  BioDrugs 06/2013;
• Article: Peptide-Mediated Targeting of Cytokines to Tumor Vasculature: The NGR-hTNF Example.

  Angelo Corti, Flavio Curnis, Gilda Rossoni, Fabrizio Marcucci, Vanesa Gregorc
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  ABSTRACT: A growing body of evidence suggests that the efficacy of cytokines in cancer therapy can be increased by targeting strategies based on conjugation with ligands that recognize receptors expressed by tumor cells or elements of the tumor microenvironment, including the tumor vasculature. The targeting approach is generally conceived to permit administration of low, yet pharmacologically active, doses of drugs, thereby avoiding toxic reactions. However, it is becoming clear that, in the case of cytokines, this strategy has another inherent advantage, i.e. the possibility of administering extremely low doses that do not activate systemic counter-regulatory mechanisms, which may limit their potential therapeutic effects. This review is focused on the use of tumor vasculature-homing peptides as vehicles for targeted delivery of cytokines to tumor blood vessel. In particular, we provide an overview of peptide-cytokine conjugates made with peptides containing the NGR, RGD, isoDGR or RGR sequences and describe, in more details, the biological and pharmacological properties of NGR-hTNF, a peptide-tumor necrosis factor-α conjugate that is currently being tested in phase II and III clinical studies. The results of preclinical and clinical studies performed with these products suggest that peptide-mediated vascular-targeting is indeed a viable strategy for delivering bioactive amounts of cytokines to tumor endothelial cells without causing the activation of counter-regulatory mechanisms and toxic reactions.
  BioDrugs 06/2013;
• Article: Bevacizumab Combination Therapy: A Review of its Use in Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

  Sohita Dhillon
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  ABSTRACT: Bevacizumab (Avastin(®)) is a recombinant, humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody that neutralizes the biological activity of VEGF and inhibits tumor angiogenesis. In the EU, in adult patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, bevacizumab (in combination with carboplatin and paclitaxel) is approved for the first-line treatment of advanced disease and (in combination with carboplatin and gemcitabine) is approved for the treatment of patients with first recurrence of platinum-sensitive disease who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. This article summarizes the pharmacology of bevacizumab and reviews the efficacy and tolerability of bevacizumab combination therapy in well-designed clinical studies in these indications. The addition of bevacizumab to first-line carboplatin plus paclitaxel, followed by bevacizumab maintenance therapy significantly prolonged progression-free survival in women with newly-diagnosed advanced disease (GOG-0218 and ICON7 studies). Progression-free survival was also significantly prolonged after second-line treatment with bevacizumab in combination with carboplatin and gemcitabine, followed by maintenance treatment with bevacizumab alone in women with recurrence (≥6 months after front-line platinum-based therapy) of platinum-sensitive disease (OCEANS study). Bevacizumab combination therapy had a generally acceptable tolerability profile in these studies, with the nature of adverse events generally similar to that observed in previous clinical trials in patients with other solid tumors. Although several unanswered questions remain, such as the optimal dosage and duration of treatment, current evidence suggests that bevacizumab combination therapy extends the treatment options available for patients with ovarian cancer.
  BioDrugs 06/2013;
• Article: Therapeutic Potential of Targeting Interleukin 5 in Asthma.

  Garry M Walsh
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  ABSTRACT: It is recognised that airway inflammation is key to asthma pathogenesis. Biopharmaceutical approaches have identified new therapies that target key cells and mediators that drive the inflammatory responses in the asthmatic lung. Such an approach resulted in the development of biologics targeted at inhibition of interleukin (IL)-4, IL-5 and IL-13. However, early clinical trials with these biologics in patients with asthma were, for the most part, disappointing even though they were highly effective in animal models of asthma. It is becoming apparent that significant clinical effects with anti-cytokine-based therapies are more likely in carefully selected patient populations that take asthma phenotypes into account. The development of discriminatory biomarkers and genetic profiling may aid identification of such patients with asthma. This review summarises the current evidence, demonstrating the effectiveness or otherwise of the targeting of IL-5 in patients with asthma.
  BioDrugs 06/2013;
• Article: Immune Globulin (Human) 10 % Liquid: A Review of its Use in Primary Immunodeficiency Disorders.

  Paul L McCormack
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  ABSTRACT: Human immune globulin (IG) 10 % liquid (Gammagard Liquid(®)) is a ready-to-use, highly purified, and concentrated immunoglobulin (Ig)G solution approved in the US for both intravenous and subcutaneous antibody replacement therapy in patients aged ≥2 years with primary humoral immunodeficiency. Intravenous IG 10 % liquid every 3-4 weeks for ≥12 months, at median serum IgG trough levels of 9.6-11.2 g/L, completely prevented acute serious bacterial infections (SBIs) in a phase III clinical trial. Weekly subcutaneous IG 10 % liquid at a dose equal to 137 % of the equivalent weekly intravenous dose, which was earlier determined to produce the same IgG exposure, produced higher serum trough IgG levels and lower peak IgG levels than intravenous administration, and also effectively reduced SBIs; the infection rate was 0.067 SBIs/subject/year, which met the US FDA efficacy criterion of <1 SBI/subject/year. The rates for non-serious infections of any kind were low for both intravenous and subcutaneous therapy. Both intravenous and subcutaneous IG 10 % liquid were safe and generally well tolerated. Systemic adverse reactions were more frequent with intravenous therapy and local infusion-site reactions were more frequent with subcutaneous therapy, but the latter reduced over time. Most adverse reactions were of mild or moderate intensity. Thus, IG 10 % liquid is an effective and generally well-tolerated preparation for both intravenous and subcutaneous IgG replacement therapy in patients with primary immunodeficiency disorders involving antibody deficiency. It offers the benefits of a ready-to-use, liquid preparation and the convenience of home-based therapy in appropriate patients.
  BioDrugs 05/2013;
• Article: Targeting CD22 in B-cell Malignancies: Current Status and Clinical Outlook.

  Loretta Sullivan-Chang, Robert T O'Donnell, Joseph M Tuscano
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  ABSTRACT: CD22 is a B-cell-specific transmembrane glycoprotein found on the surface of most B cells; it modulates B-cell function, survival and apoptosis. CD22 has emerged as an ideal target for monoclonal antibody (mAb)-based therapy of B-cell malignancies including most lymphomas and many leukemias. Epratuzumab, an anti-CD22 mAb, has been developed in various forms, including as an unlabeled (naked) mAb, as a radioimmunotherapeutic, as an antibody drug conjugate (ADC), and as a vehicle for CD22-targeted nanoparticles. While clinical trials with unlabeled epratuzumab have demonstrated modest results, its combination with rituximab in phase II studies has been more encouraging. Based on the potential for CD22 to become internalized, CD22-targeted constructs carrying radioisotopes or toxins have generated promising results. Radioimmunotherapy, utilizing (90)Y-labeled epratuzumab, was shown to be highly effective in patients with follicular lymphoma, generating a complete response (CR) rate of 92 % and progression-free survival of more than 2 years. ADC therapy is a promising therapeutic approach to B-cell malignancies which includes the direct conjugation of mAbs with cytotoxic agents. Phase II studies of inotuzumab ozogamicin, an ADC which combines anti-CD22 mAb with calicheamicin, an enediyne antibiotic which mediates apoptosis, in patients with acute lymphoblastic leukemia have produced an overall response rate (ORR) of greater than 50 % in treatment-refractory patients. Phase I trials of moxetumomab pasudotox, an ADC which combines anti-CD22 with PE38, a fragment of Pseudomonas exotoxin A, have been completed in hairy cell leukemia with a ORR of 86 %. Finally, a review of CD22-targeted nanoparticles, that include a doxorubicin-containing lipid complex that uses synthetic high-affinity CD22 ligand mimetics as well as anti-CD22 mAb-coated pegylated liposomas doxorubin (PLD), has demonstrated promising results in pre-clinical models of human lymphoma. Moreover, novel anti-CD22 mAb that block CD22 ligand binding as well as second generation ADC that utilize biodegradable linkers and more potent toxins hold great hope for the future of CD22-targeted therapeutics that may translate into better outcomes for patients with CD22-positive malignancies.
  BioDrugs 05/2013;
• Article: Everolimus: A Guide to Its Use in Liver Transplantation.

  Gillian M Keating, Katherine A Lyseng-Williamson
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  ABSTRACT: The mammalian target of rapamycin inhibitor everolimus (Zortress(®), Certican(®)) was recently approved in the USA and a number of EU countries for use in combination with a reduced dosage of tacrolimus and corticosteroids for the prophylaxis of organ rejection in adult liver transplant recipients. Compared with standard-exposure tacrolimus, early use of everolimus plus a reduced dosage of tacrolimus did not compromise efficacy in liver transplant recipients. In addition, significantly better renal function with everolimus plus reduced-exposure tacrolimus than with standard-exposure tacrolimus was seen from 6 weeks post-transplant onwards. Everolimus plus reduced-exposure tacrolimus has an acceptable tolerability profile in liver transplant recipients.
  BioDrugs 05/2013;
• Article: Evolving Approaches to Metastatic Breast Cancer Patients Pre-treated with Anthracycline and Taxane.

  Shigehira Saji
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  ABSTRACT: Metastatic breast cancer is currently incurable and the goals of therapy focus on prolonging survival and maintaining quality of life by controlling symptoms and minimizing toxicity. Treatments for metastatic breast cancer include chemotherapeutic agents from various classes, such as taxanes, vinca alkaloids, anthracyclines and antimetabolites. This review provides an overview of chemotherapeutic agents for the treatment of metastatic breast cancer patients previously treated with anthracyclines and taxanes, focusing on a clinical evaluation of eribulin, the most recently approved agent for the treatment of metastatic breast cancer. Eribulin is a synthetic derivative of halichondrin B, a tumour growth inhibitor found in marine sponges, which prevents microtubule growth and sequesters the tubulin molecules into unusual aggregates, initiating apoptosis. Studies of eribulin have shown that the drug is effective in the treatment of previously treated metastatic breast cancer, and has an acceptable toxicity profile. Importantly, in the phase III EMBRACE study, eribulin treatment resulted in a survival advantage, a difficult endpoint to achieve with a single chemotherapeutic agent. An additional phase III study showed that eribulin has similar efficacy to capecitabine in women treated with no more than three prior therapies. Furthermore, pre-specified exploratory analyses suggest that particular patient subgroups may have greater therapeutic benefit with eribulin and may warrant further study to explore the potential mechanisms.
  BioDrugs 05/2013;
• Article: Cationic Host Defence Peptides: Potential as Antiviral Therapeutics.

  Emily Gwyer Findlay, Silke M Currie, Donald J Davidson
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  ABSTRACT: There is a pressing need to develop new antiviral treatments; of the 60 drugs currently available, half are aimed at HIV-1 and the remainder target only a further six viruses. This demand has led to the emergence of possible peptide therapies, with 15 currently in clinical trials. Advancements in understanding the antiviral potential of naturally occurring host defence peptides highlights the potential of a whole new class of molecules to be considered as antiviral therapeutics. Cationic host defence peptides, such as defensins and cathelicidins, are important components of innate immunity with antimicrobial and immunomodulatory capabilities. In recent years they have also been shown to be natural, broad-spectrum antivirals against both enveloped and non-enveloped viruses, including HIV-1, influenza virus, respiratory syncytial virus and herpes simplex virus. Here we review the antiviral properties of several families of these host peptides and their potential to inform the design of novel therapeutics.
  BioDrugs 05/2013;
• Article: Canakinumab: A Guide to Its Use in Acute Gouty Arthritis Flares.

  Katherine A Lyseng-Williamson
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  ABSTRACT: Canakinumab (Ilaris(®)), an anti-interleukin-1β monoclonal antibody, is a novel approach to treat acute gouty arthritis flares in a targeted population of patients in whom treatment options are limited. Relative to on-demand treatment with intramuscular triamcinolone acetonide 40 mg, on-demand treatment with subcutaneous canakinumab 150 mg significantly relieved the pain and inflammation of a new gout flare, and reduced the risk of new flares in patients with acute gouty arthritis flares in whom standard treatment with non-steroidal anti-inflammatories and/or colchicine was inappropriate. Canakinumab has an acceptable tolerability profile in this difficult-to-treat population. The increased risk of infections and neutropenia associated with canakinumab treatment can be minimized by following the recommended precautions.
  BioDrugs 05/2013;
• Article: Physicochemical and Functional Comparability Between the Proposed Biosimilar Rituximab GP2013 and Originator Rituximab.

  Jan Visser, Isabel Feuerstein, Thomas Stangler, Timo Schmiederer, Cornelius Fritsch, Martin Schiestl
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  ABSTRACT: BACKGROUND: Regulatory approval for a biosimilar product is provided on the basis of its comparability to an originator product. A thorough physicochemical and functional comparability exercise is a key element in demonstrating biosimilarity. Here we report the characterization of a proposed biosimilar rituximab (GP2013) and originator rituximab. OBJECTIVE: To compare GP2013 with originator rituximab using an extensive array of routine analytical and extended characterization methods. METHODS: Primary and higher order protein structures were analyzed using a variety of methods that included high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS), peptide mapping with UV and MS detection, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, hydrogen deuterium exchange (HDX) MS, 1D (1)H nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and differential scanning calorimetry (DSC). Charge and amino acid modifications were assessed using cation exchange chromatography (CEX) and peptide mapping using reversed-phase (RP) HPLC. Boronate affinity chromatography was used to determine the relative amount of glycation. Glycans were identified and quantified after 2-aminobenzamide (2-AB) labeling and separation using normal phase HPLC with fluorescence and MS detection, respectively. Glycan site occupancy was determined using reducing capillary electrophoresis with sodium dodecyl sulfate (CE-SDS). Size heterogeneity was determined using reducing and non-reducing CE-SDS, size exclusion chromatography (SEC) and asymmetric flow field flow fractionation (AF4). Biological characterization included a series of bioassays (in vitro target binding, antibody-dependent cell-mediated cytotoxicity [ADCC], complement-dependent cytotoxicity [CDC] and apoptosis) and surface plasmon resonance (SPR) Fc receptor binding assays. RESULTS: Intact mass analysis of GP2013 and the heavy and light chains using RP HPLC-ESI-MS revealed the expected molecular mass of rituximab. The amino acid sequence was shown to be identical between GP2013 and the originator rituximab. Further sequence confirmation using RP-HPLC-UV/MS peptide mapping showed non-distinguishable chromatograms for Lys-C digested GP2013 and originator rituximab. The higher order structure of GP2013 was shown to be indistinguishable from originator rituximab using a large panel of redundant and orthogonal methods. GP2013 and originator rituximab were comparable with regard to charge variants, specific amino acid modifications and the glycan pattern. GP2013 was also shown to have similar purity, aggregate and particle levels when compared with the originator. Functionally, and by using a comprehensive set of bioassays and binding assays covering a broad range of rituximab's functional activities, GP2013 could not be distinguished from originator rituximab. CONCLUSION: GP2013 was shown to be physicochemically highly similar to originator rituximab at the level of primary and higher order structure, post-translational modifications and size variants. An extensive functional characterization package indicated that GP2013 has the same biological properties as originator rituximab.
  BioDrugs 05/2013;
• Article: The Th17 Pathway as a Therapeutic Target in Rheumatoid Arthritis and Other Autoimmune and Inflammatory Disorders.

  Debbie M Roeleveld, Annemarie E M van Nieuwenhuijze, Wim B van den Berg, Marije I Koenders
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  ABSTRACT: Production of the pro-inflammatory cytokine interleukin (IL)-17 by Th17 cells and other cells of the immune system protects the host against bacterial and fungal infections, but also promotes the development of rheumatoid arthritis (RA) and other autoimmune and inflammatory disorders. Several biologicals targeting IL-17, the IL-17 receptor, or IL-17-related pathways are being tested in clinical trials, and might ultimately lead to better treatment for patients suffering from various IL-17-mediated disorders. In this review, we provide a clear overview of current knowledge on Th17 cell regulation and the main Th17 effector cytokines in relation to IL-17-mediated conditions, as well as on recent IL-17-related drug developments. We demonstrate that targeting the Th17 pathway is a promising treatment for rheumatoid arthritis and various other autoimmune and inflammatory diseases. However, improvements in technical developments assisting in the identification of patients suffering from IL-17-driven disease are needed to enable the application of tailor-made, personalized medicine.
  BioDrugs 04/2013;
• Article: A Review of Dendritic Cell Therapy for Cancer: Progress and Challenges.

  Gina M Mantia-Smaldone, Christina S Chu
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  ABSTRACT: Dendritic cells are the professional antigen-presenting cells of the innate immune system with the potential to generate robust antigen-specific T cell immune responses. Immunotherapeutic strategies have attempted to monopolize on this ability of dendritic cells to deliver antigens as a means of therapeutic vaccination in individuals with advanced malignancies. Since the publication of the first clinical trial in melanoma patients in 1995, therapeutic dendritic cell cancer vaccines have been extensively studied in numerous phase I and II trials. While advances have been encountered (especially with prostate cancer), there are still considerable challenges that need to be addressed in future clinical trials. In this review, we describe the current methodology and highlight trials which have contributed to the development of dendritic cell vaccines. We then review strategies to optimize dendritic cell vaccines in order to improve antitumor responses in cancer patients.
  BioDrugs 04/2013;
• Article: Genome-Based Bacterial Vaccines: Current State and Future Outlook.

  Alexandra Schubert-Unkmeir, Myron Christodoulides
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  ABSTRACT: Genome-based reverse vaccinology (RV) is a multi-step experimental strategy which starts from in silico analysis of whole genome sequences, from which vaccine candidates can be selected by using bioinformatic algorithms to identify putative protective antigens. In this review, we examine the current state of genome-based RV-engineered vaccines and future applications. The first product of genome-based RV is Bexsero(®), a vaccine developed for preventing Neisseria meningitidis serogroup B infection, and the strategy is currently being used for the development of new vaccines for other obdurate and emerging bacterial diseases. Improved sequencing technologies and the ongoing whole-genome sequence analyses of helminths, protozoa, and ectoparasites also currently serve as a basis for an RV strategy to produce new potential vaccines against eukaryotic pathogens. We also highlight an emerging approach-structure-based vaccinology-that exploits the information derived from the determined three-dimensional structures of vaccine candidates. Regardless, genome-based RV and other vaccine discovery platforms still depend on empirical experimental science to glean, from the hundreds of identified antigens from any one pathogen, those that should be combined to produce an effective vaccine.
  BioDrugs 04/2013;
• Article: Adalimumab: A Review of Its Use in the Treatment of Patients with Ulcerative Colitis.

  Celeste B Burness, Gillian M Keating
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  ABSTRACT: Adalimumab is a fully human, recombinant, monoclonal IgG1 antibody specific for the cytokine tumor necrosis factor-α. It is approved for the treatment of patients with inflammatory diseases, including adults with moderately to severely active ulcerative colitis who are refractory to, or intolerant of, corticosteroids and/or immunomodulators. In two well-designed 8- and 52-week clinical trials in patients with moderately to severely active ulcerative colitis despite treatment with corticosteroids and/or immunomodulators, subcutaneous adalimumab (160 mg, week 0; 80 mg, week 2; 40 mg every other week starting at week 4) was more effective than placebo for inducing and maintaining clinical remission. A statistically significant effect size (albeit <10 %) over placebo for the remission per Mayo score (primary endpoint) was observed with adalimumab at 8 weeks in both trials and at 52 weeks in one trial. Compared with placebo, adalimumab was associated with reductions in hospitalizations and improvements in other secondary endpoints, including clinical response, mucosal healing, corticosteroid-sparing, and health-related quality of life measures. Additionally, an early response to adalimumab was shown to be predictive of long-term efficacy. Adalimumab was generally well tolerated, compared with placebo, during clinical trials in patients with ulcerative colitis; the adverse event profile was similar to that in patients with Crohn's disease or other approved indications. Adalimumab provides a new treatment option for patients with moderately to severely active ulcerative colitis who are refractory to, or intolerant of, corticosteroids and/or immunomodulators.
  BioDrugs 04/2013;
• Article: Therapeutic Potential of Regulatory T cells in Autoimmune Disorders.

  Johannes Fessler, Anja Felber, Christina Duftner, Christian Dejaco
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  ABSTRACT: Regulatory T cells (Tregs) play a dominant role in the regulation of immune responses. Quantitative and/or qualitative abnormalities of Tregs were observed in patients with autoimmune diseases and therapeutic interventions focusing Tregs are an attractive new target with the potential to cure these disorders. Biological agents approved for treatment of inflammatory rheumatic diseases transiently influence Treg prevalences and function and experimental therapies including novel biological agents, gene therapy, activation and ex vivo expansion of purified Tregs as well as substances influencing tolerogenic dendritic cells will be developed for selective Treg therapy. Although many of these interventions are effective in vitro, in animal models as well as in early clinical trials, significant concerns exist regarding the stability of Treg modifications as well as the long-term safety of Treg-based therapies.
  BioDrugs 04/2013;
• Article: Therapeutic Strategies in Psoriasis Patients with Psoriatic Arthritis: Focus on New Agents.

  Emily Yiping Gan, Wei-Sheng Chong, Hong Liang Tey
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  ABSTRACT: Psoriatic arthritis affects approximately 6-42 % of patients with psoriasis. It is useful for physicians or dermatologists managing psoriasis patients to be aware of how to concurrently manage the joint manifestations, as it is preferable and convenient to use a single agent in such patients. However, only certain therapies are effective for both. Systemic agents, which can be used for both skin and joint manifestations, include methotrexate and ciclosporin. For the group of biologic agents, the tumor necrosis factor inhibitors such as adalimumab, etanercept, infliximab, golimumab and certolizumab are effective. Ustekinumab is a more recently developed agent belonging to the group of anti-IL-12p40 antibodies and has been shown to be efficacious. Newer drugs in the treatment armamentarium that have shown efficacy for both psoriasis and psoriatic arthritis consist of the anti-IL-17 agent, secukinumab, and a phosphodiesterase-4 inhibitor, apremilast. The other anti-IL-17 agents, ixekizumab and brodalumab, as well as the oral Jak inhibitor, tofacitinib, have very limited but promising data. This review paper provides a good overview of the agents that can be used for the concurrent management of skin and joint psoriasis.
  BioDrugs 04/2013;
• Article: Multicomponent Meningococcal Serogroup B Vaccine (4CMenB; Bexsero(®)): A Review of its Use in Primary and Booster Vaccination.

  Natalie J Carter
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  ABSTRACT: Multicomponent meningococcal serogroup B vaccine (4CMenB; Bexsero(®)) is a unique vaccine containing four main immunogenic components: three recombinant proteins combined with outer membrane vesicles derived from meningococcal NZ98/254 strain. After three doses of 4CMenB (administered at 2, 3, and 4 months or 2, 4, and 6 months of age) in vaccine-naive infants, the majority of infants had seroprotective human complement serum bactericidal assay (hSBA) antibody titers against the meningococcal serogroup B test strains selected to be specific for the vaccine antigens in randomized, open-label or observer-blind, multicenter, phase IIb or III trials. In extensions to the phase III trial, two doses of 4CMenB administered between 12 and 15 months of age in vaccine-naive infants, and a single booster dose of 4CMenB administered at 12 months of age in vaccine-experienced infants, also elicited robust immunogenic responses. In a phase IIb/III trial, the majority of adolescents (aged 11-17 years) achieved seroprotective hSBA antibody titers against meningococcal serogroup B test strains after two doses of 4CMenB, and a third dose did not appear to add any extra protection. In adults who were potentially at an increased risk of occupational exposure to meningococcal isolates, seroprotection rates were high after one dose of 4CMenB and increased further after two or three doses in a small noncomparative, two-center, phase II trial. The reactogenicity of 4CMenB was generally acceptable in clinical trials. However, the vaccine was associated with more solicited systemic adverse events (particularly fever) in infants when coadministered with routine infant vaccines than when these vaccines were administered alone. In conclusion, 4CMenB effectively elicited immune responses against meningococcal serogroup B test strains selected to be specific for the vaccine antigens in infants, adolescents, and adults.
  BioDrugs 04/2013;