Current Pharmaceutical Biotechnology - Volume 18, Issue 12, 2017

Background: Psoriasis is a chronic immune-mediated inflammatory disorder, with an estimated global prevalence of 2-3%. Psoriasis is associated with an impaired health-related quality of life and a substantial economic burden. Biologics, which target the pathways involved in the pathogenesis of psoriasis, represent an established therapeutic approach for moderate-to-severe plaque psoriasis, with remarkable efficacy and safety profile extensively examined and monitored. Methods: Biological therapies currently available can be divided into three main categories: the TNFα antagonists (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol), the interleukin (IL)- 12/23 monoclonal antibody (ustekinumab), and IL-17 inhibitor (secukinumab, ixekizumab). Results: In this section, we explore the complex role of TNFα in psoriasis as well as the efficacy and safety of TNFα inhibitors largely used in the management of the cutaneous disease. Conclusion: Dosing regimens, administration, pharmacodynamics profiles, efficacy, and safety of licensed anti-TNFα are here discussed in detail.

Background: Psoriasis is a chronic immune-mediated inflammatory skin disorder that is estimated to affect 2-3% of the general population. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Methods: Biologics licensed for psoriasis include the TNFα inhibitors (infliximab, adalimumab, etanercept), the interleukin (IL)-12/23 monoclonal antibody (ustekinumab), and IL-17 inhibitor (secukinumab, ixekizumab). Results: In this section, we analyse the role of IL-12, IL-23, and IL-17 in psoriasis and evaluated the efficacy and safety of biologic therapies targeting this cytokine. Conclusion: Dosing regimens, administration modality, and pharmacodynamics profiles of currently available anti-IL-12/IL-23 and IL-17 inhibitors are also examined.

Background: Abstract: Up to 80% of Crohn's disease (CD) patients require at least one surgical intervention in their lifetime and up to 70% of these patients develop postoperative endoscopic recurrence within 1 year. Methods: The most important predictors of early postoperative recurrence are represented by smoking, prior intestinal surgery, penetrating disease and perianal location. Genetic factors, gut microbiota structure and immunological alterations may be involved in the pathogenesis of postoperative recurrence of CD, although their specific roles have to be determined yet. Results: Different drugs, such as metronidazole, thiopurines and anti-tumor necrosis factor α (anti- TNFα) have been shown to reduce the risk of recurrence in many clinical trials, although the choice of the drug should take into consideration the benefits, the potential side effects and also the costs. Patients who are at high risk for postoperative recurrence should be considered for early medical prophylaxis with thiopurines or anti-TNFα drugs; on the contrary, patients who do not have risk factors may receive no treatment or receive a course of antibiotic or mesalazine followed by tailored therapy based on endoscopy at 6 months. Conclusion: Therefore, stratifying patients according to their risk of recurrence and tailoring therapy are at present the ideal and most cost-effective ways to treat operated CD patients, although many aspects require further evaluation.

Background: Biologic drugs, introduced in clinical practice almost twenty years ago, represent nowadays a prominent treatment option in patients with chronic inflammatory arthritis, such as Rheumatoid Arthritis, Psoriatic Arthritis and Spondyloarthritis, that include ankylosing spondylitis and non-radiographic axial spondyloarthritis. Methods: Several compounds targeting different pathways have been marketed and approved for the treatment of inflammatory arthritis, with a significant impact on the clinical outcomes and the natural history of the diseases. Results: There are currently seven classes of biologics that are available for the treatment of inflammatory arthritis, each inhibiting a different aspect of the immune-driven inflammatory pathway. They include: • Tumor Necrosis Factor (TNF) inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol); • Interleukin-1 (IL-1) receptor antagonists (anakinra); • Interleukin-6 (IL-6) inhibition (tocilizumab); • Interleukin-12/23 (IL23) inhibition (ustekinumab); • Interleukin-17 (IL-17) inhibition (secukinumab); • B-cell inhibition (anti-CD20, rituximab); • T-cell costimulation inhibition (anti-CTLA-4, abatacept). Conclusion: In this review, we will focus on the role of biologic drugs in the treatment strategies for inflammatory arthritis.

Background: The use of biologic agents in systemic immune-mediated diseases has dramatically increased in recent years, replacing conventional immunosuppressive strategies that are characterized by unspecific mechanisms of action and burdened with serious adverse effects. Biologic drugs have selective action towards specific targets, with considerable steroid-sparing effect. They are used nowadays to induce remission or treat specific organ involvements in systemic autoimmune diseases. Conclusion: In this review, we will discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the conventional drugs.

Background: Microgeographic studies of molecular markers could reveal the nature and dynamics of genetic diversity and the evolutionary driving forces shaping evolution. Methods: The microclimatic genetic divergence of wild emmer wheat associated with solar radiation was investigated, in the present study, using multiple types of molecular markers including allozyme, amplified polymorphic DNA (RAPD), simple sequence repeat (SSR), and single nucleotide polymorphisms (SNP). The studies included two climatic microniches: (1) sunny between oak trees; and (2) shady under the canopies of oak trees. Results: All four types of markers showed a similar microniche tendency of genetic variance, i.e., lower in the shady than in the sunny niche. Significant genetic divergence at some loci including allozyme, RAPD, SSR, and SNP was detected between the two climatic microniches, and also, the observed genetic differentiation is mainly due to natural selection. Based on different FST outlier detection algorithms, there were 21 candidate loci subjected to positive selection. Importantly, most of the identified candidate loci were mapped in the selection “hot spots” of wheat genome. Conclusion: The present work implies that microclimatic selection appears to play an important role either in the protein-coding region or in the non-coding region of wheat genomes, and hence, highlights the evolutionary theory of natural selection.