Drugs

Harris, Vanessa

doi: 10.1007/s40265-018-0941-3pmid: 29943376

Despite unprecedented advances in understanding the intestinal microbiome, its potential to improve fields such as vaccinology has yet to be realized. This review briefly outlines the immunologic potential of the intestinal microbiome for vaccinology and highlights areas where the microbiome holds specific promise in vaccinology. Oral rotavirus vaccine effectiveness in low-income countries is used as a case study to describe how the intestinal microbiome may be employed to improve a vaccine’s immunogenicity. A top-down, evidence-based approach is proposed to identify effective microbiota-based applications for vaccine improvement. Applying evidence from field studies in pertinent populations that correlate microbiome composition with vaccine effectiveness to appropriate experimental platforms will lead to the identification of safe, vaccine-supporting microbiota targets that are relevant to populations in need of improvement in vaccine-induced immunity.

Afsar, Baris; Covic, Adrian; Ortiz, Alberto; Afsar, Rengin; Kanbay, Mehmet

doi: 10.1007/s40265-018-0942-2pmid: 29968152

Interleukin (IL)-1α and IL-1β are proinflammatory cytokines that play a role in many diseases such as rheumatoid arthritis, juvenile rheumatoid arthritis, gout, and periodic inflammatory syndromes, including familial Mediterranean fever and Muckle-Wells syndrome. Drugs targeting IL-1 such as recombinant IL-1Ra (anakinra), neutralizing anti-IL-1β antibodies (canakinumab) and IL-1β traps (rilonacept) are in clinical use to treat these diseases. Additionally, experimental evidence suggests a role of IL-1 in kidney disease and hypertension and targeting IL-1 showed promising results in high cardiovascular risk patients, hemodialysis and renal transplantation patients. We now summarize knowledge on the potential role of IL-1 targeting in patients with kidney disease.

Meesing, Atibordee; Razonable, Raymund R.

doi: 10.1007/s40265-018-0943-1pmid: 29961185

Cytomegalovirus (CMV) continues to be one of the most important pathogens that universally affect solid organ and allogeneic hematopoietic stem cell transplant recipients. Lack of effective CMV-specific immunity is the common factor that predisposes to the risk of CMV reactivation and clinical disease after transplantation. Antiviral drugs are the cornerstone for prevention and treatment of CMV infection and disease. Over the years, the CMV DNA polymerase inhibitor, ganciclovir (and valganciclovir), have served as the backbone for management, while foscarnet and cidofovir are reserved for the management of CMV infection that is refractory or resistant to ganciclovir treatment. In this review, we highlight the role of the newly approved drug, letermovir, a viral terminase inhibitor, for CMV prevention after allogeneic hematopoietic stem cell transplantation. Advances in immunologic monitoring may allow for an individualized approach to management of CMV after transplantation. Specifically, the potential role of CMV-specific T-cell measurements in guiding the need for the treatment of asymptomatic CMV infection and the duration of treatment of CMV disease is discussed. The role of adoptive immunotherapy, using ex vivo-generated CMV-specific T cells, is highlighted. This article provides a review of novel drugs, tests, and strategies in optimizing our current approaches to prevention and treatment of CMV in transplant recipients.

Danielak, Dorota; Karaźniewicz-Łada, Marta; Główka, Franciszek

doi: 10.1007/s40265-018-0947-xpmid: 30003466

The introduction of ticagrelor, one of the first directly-acting oral antiplatelet drugs, provided new possibilities in the prevention of thrombotic events in patients with acute coronary syndromes (ACS). Current guidelines recommend ticagrelor in dual antiplatelet therapy with aspirin over clopidogrel for prevention of stent thrombosis in patients with ACS. Moreover, in the management of ACS, lipid-lowering treatment with high-intensity statin therapy is advised for secondary prevention of cardiovascular events over the long term. Despite the apparent advantages of combined antiplatelet and lipid-lowering treatments, a possible interaction between statins and ticagrelor may lead to myopathy and rhabdomyolysis. In this review, relevant information was gathered on the ticagrelor-statin interaction that might lead to this life-threatening condition. This review focuses on the most widely used statins—simvastatin, atorvastatin, and rosuvastatin. Possible mechanisms of this interaction are discussed, including CYP3A4 isoenzymes, organic anion transporter polypeptide (OATPs), P-glycoprotein and glucuronidation. PubMed database was searched for relevant case reports and all data gathered from the introduction of ticagrelor to March 2018 are presented and discussed. In summary, co-administration of statins and ticagrelor was found to be relatively safe in routinely prescribed doses. However, caution should be exercised, especially in elder populations.

Coulter, Ann; Rebello, Candida; Greenway, Frank

doi: 10.1007/s40265-018-0946-ypmid: 30014268

For many years, obesity was believed to be a condition of overeating that could be resolved through counseling and short-term drug treatment. Obesity was not recognized as a chronic disease until 1985 by the scientific community, and 2013 by the medical community. Pharmacotherapy for obesity has advanced remarkably since the first class of drugs, amphetamines, were approved for short-term use. Most amphetamines were removed from the obesity market due to adverse events and potential for addiction, and it became apparent that obesity pharmacotherapies were needed that could safely be administered over the long term. This review of central nervous system (CNS) acting anti-obesity drugs evaluates current therapies such as phentermine/topiramate, which act through multiple neurotransmitter pathways to reduce appetite. In the synergistic mechanism of bupropion/naltrexone, naltrexone blocks the feed-back inhibitory circuit of bupropion to give greater weight loss. Lorcaserin, a selective agonist of a serotonin receptor that regulates food intake, and the glucagon-like-peptide-1 (GLP-1) receptor agonist liraglutide are reviewed. Future drugs include tesofensine, a potent triple reuptake inhibitor in Phase III trials for obesity, and semaglutide, an oral GLP-1 analog approved for diabetes and currently in trials for obesity. Another potential new pharmacotherapy, setmelanotide, is a melanocortin-4 receptor agonist, which is still in an early stage of development. As our understanding of the communication between the CNS, gut, adipose tissue, and other organs evolves, it is anticipated that obesity drug development will move toward new centrally acting combinations and then to drugs acting on peripheral target tissues.

Dhillon, Sohita

doi: 10.1007/s40265-018-0938-ypmid: 29943375

Regorafenib (Stivarga®) is an oral small-molecule multiple kinase inhibitor. It is indicated worldwide for patients with metastatic colorectal cancer (mCRC). In the EU and USA it is indicated for patients with mCRC who have been previously treated with, or are not considered candidates for available therapies, including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and, if RAS wild-type, an anti-EGFR therapy. In Japan, it is indicated for the treatment of unresectable, advanced/recurrent CRC. The addition of regorafenib to best supportive care prolonged median overall survival (OS; by up to 2.5 months) and progression-free survival (PFS; by up to 1.5 months) relative to the addition of placebo in double-blind phase 3 studies (CORRECT and CONCUR) in patients with mCRC who had progressed after failure of standard therapy. Health-related quality of life was not adversely affected with regorafenib relative to placebo. A large open-label phase 3 study (CONSIGN) and several large real-world studies supported the efficacy of regorafenib in this setting. Regorafenib had a generally manageable tolerability profile, which was consistent with the profile of a typical small-molecule multiple kinase inhibitor. Treatment-related adverse events (AEs), mostly of mild or moderate severity, were reported in the majority of patients receiving regorafenib, with dermatological toxicities and liver enzyme elevations among the most common AEs. Although identification of biomarkers/parameters predicting efficacy outcomes with regorafenib will help to individualize therapy, current evidence indicates that regorafenib is a valuable treatment option for patients with refractory mCRC who have a very poor prognosis.

Frampton, James; Basset-Séguin, Nicole

doi: 10.1007/s40265-018-0948-9pmid: 30030732

Vismodegib (Erivedge®) is the first-in-class, oral small molecule inhibitor of the Hedgehog (Hh) pathway, abnormal activation of which is associated with basal cell carcinoma (BCC). In the USA, vismodegib is indicated for the treatment of adults with metastatic BCC (mBCC) or with locally-advanced BCC (LaBCC) that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Similarly, in the EU, vismodegib is indicated for the treatment of adult patients with symptomatic mBCC, or with laBCC inappropriate for surgery or radiotherapy. The full European approval of vismodegib was based on the results of two phase II, open-label, noncomparative, international trials (ERIVANCE BCC and STEVIE), both of which showed high rates of tumour control in the indicated patient populations, including individuals with or without Gorlin syndrome. These studies also showed that vismodegib has an acceptable and manageable tolerability profile characterized by a number of class-related treatment-emergent adverse events, including muscle spasms, taste disturbances, alopecia, weight loss and asthenia (fatigue). Primary and secondary resistance to vismodegib has been documented, albeit at a low rate compared with some other targeted therapies. Vismodegib is therefore an effective and generally well tolerated systemic therapy for patients with mBCC and laBCC that can no longer be suitably controlled with surgery and/or radiotherapy. Historically, it is the first member of a class of drugs (Hh pathway inhibitors) that are now considered to be first-line treatment options for such individuals.

Markham, Anthony

doi: 10.1007/s40265-018-0944-0pmid: 29968151

Amgen and Novartis are developing erenumab (AIMOVIG™, erenumab-aooe)—a fully human monoclonal antibody calcitonin gene-related peptide (CGRP) receptor antagonist—for the prevention of migraine. CGRP is a vasodilatory neuropeptide implicated in the pathophysiology of migraine and treatment with erenumab was associated with significant reductions in migraine frequency in phase II and III clinical trials. Based on these positive results erenumab was recently approved in the US for the preventive treatment of migraine in adults and has received a positive opinion in the EU for the prophylaxis of migraines in adults who have at least 4 migraine days per month. This article summarizes the milestones in the development of erenumab leading to this first approval.

Shirley, Matt

doi: 10.1007/s40265-018-0949-8pmid: 29995177

Avatrombopag (Doptelet®) is an orally bioavailable, small molecule thrombopoietin receptor agonist that has been developed by Dova Pharmaceuticals for the treatment of thrombocytopenic disorders. In May 2018 avatrombopag received its first global approval, in the USA, for use in the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure. A Marketing Authorization Application for use of avatrombopag in this indication was submitted to the EMA in April 2018. Clinical development of avatrombopag in the treatment of other thrombocytopenic disorders, including immune thrombocytopenic purpura and chemotherapy-induced thrombocytopenia, is ongoing. This article summarizes the milestones in the development of avatrombopag leading to this first approval for the treatment of thrombocytopenia in adult patients with CLD.

Syed, Yahiya

doi: 10.1007/s40265-018-0951-1pmid: 30003467

The article Nonacog Beta Pegol: A Review in Haemophilia B, written by Yahiya Y. Syed, was originally published Online First without open access. After publication in volume 77, issue 18, pages 2003–2012 Novo Nordisk A/S requested that the article be Open Choice to make the article an open access publication. Post-publication open access was funded by Novo Nordisk A/S. The article is forthwith distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/ ), which permits any noncommercial use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.