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Order Tubulavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
After many important contributions to the classical molecular biology, the Inovirus members have won their remarkable place in history due to the phage display. This technique was elaborated by George P. Smith (1985) when he displayed a collection of peptides on live phage f1 libraries with following selection of one of them that was recognized by the specific antibody. The phage display was awarded with a half of the Nobel Prize in Chemistry 2018 jointly with George P. Smith and Gregory P. Winter “for the phage display of peptides and antibodies,” where the other half was awarded to Frances H. Arnold “for the directed evolution of enzymes.” As commented by the Nobel Committee, Gregory Winter used phage display for the directed evolution of antibodies, with the aim of producing new pharmaceuticals. The first one based on this method, adalimumab, was approved in 2002 and is used for rheumatoid arthritis, psoriasis and inflammatory bowel diseases. Since then, phage display has produced antibodies that can neutralize toxins, counteract autoimmune diseases and cure metastatic cancer.
Gastrointestinal diseases and pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Murtaza Arif, Anjana Sathyamurthy, Jessica Winn, Jamal A. Ibdah
Biologic therapy has opened a new era in the treatment of IBD. All three biologic agents including infliximab, adalimumab, and certolizumab are pregnancy category B. These agents inhibit the activity of tumor necrosis factor and are used for induction and maintenance of remission in IBD patients. Data on the safety of infliximab in pregnancy are limited; however, no maternal toxicity, embryotoxicity, or teratogenicity to infliximab has been observed. The two largest studies are the Crohn’s Therapy, Resource, Evaluation, and Assessment Tool (TREAT) registry and the Infliximab Safety Database (105,106). The TREAT registry is a prospective, multicenter study of CD patients. Of more than 6200 patients enrolled, 117 of 168 pregnancies were exposed to infliximab. No fetal malformations were seen. Miscarriage and neonatal complication rates were not statistically significant between the infliximab-exposed and unexposed group (105). The Infliximab Safety Database is a retrospective database that records voluntary adverse event reports associated with infliximab use. The expected versus observed outcomes among women exposed to infliximab were reported no different than those of the general population (106). In a recent case series, infliximab remained undetectable in breast milk while maternal levels remained in the therapeutic range (107). Case reports have also described successful use of adalimumab in women with CD and pregnancy (108–110).
Immune system modulators
Published in Gabriel Virella, Medical Immunology, 2019
Richard M. Silver, Stephen Elmore
TNF has been implicated as one of the primary cytokines responsible for inflammation in several diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Several different medications have been developed to inhibit TNF in a number of ways. Etanercept exists as an artificial, plasma-based version of the TNF receptor that binds to TNF before it is able to interact with cell-bound receptors and initiate the inflammatory cascade. It is typically administered as a weekly subcutaneous injection. Infliximab is a monoclonal anti-TNF antibody that is a murine/human hybrid. It functions by binding and neutralizing TNF in the plasma and is given as an IV infusion every 6–8 weeks. Due to its chimeric nature, however, use of this medication can lead to development of antichimeric antibodies that can lower the functional level of the drug, making it less effective. Adalimumab differs in that it is a fully humanized monoclonal antibody to TNF. This theoretically lowers the immunogenicity of the molecule. Adalimumab is given as a subcutaneous injection every 7–14 days. Similar to adalimumab, golimumab also is a monoclonal antibody, and its longer half-life allows the medication to be given on a monthly basis subcutaneously or every 2 months intravenously. Finally, certolizumab is another TNF inhibitor, in this case a pegylated F(ab′)2 fragment of anti-TNF antibody. Its half-life is shorter (11 days) and thus it needs to be administered initially every 2 weeks and every 4 weeks for maintenance of its effects.
Response to the Second TNF-α Inhibitor (Adalimumab or Infliximab) after Failing the First One in Refractory Idiopathic Inflammatory Retinal Vascular Leakage
Published in Ocular Immunology and Inflammation, 2022
Arash Maleki, Cristina M Garcia, Soheila Asgari, Ambika Manhapra, Charles Stephen Foster
The side effects of adalimumab in both groups included increased respiratory infections in one patient, painful injections in one patient, injection site reaction in one patient, fatigue and weakness in one patient, sinus infection and ear infection in one patient, and skin rash in one patient. The side effects of infliximab included skin rash in one patient, gastrointestinal symptoms in one patient, drug-induced lupus in one patient, pneumonia and deep vein thrombosis in one patient, and infusion reaction [anaphylactoid reaction: moderate immediate infusion reaction (chest tightness, urticarial, hypertension, and fever)] in one patient. The latter patient was treated successfully with discontinuing infliximab infusion a combination of oral acetaminophen, intramuscular anti-histamine, and intravenous corticosteroids.
Clinical Follow-up of Patients with Behçet Uveitis after Discontinuation of Infliximab Therapy
Published in Ocular Immunology and Inflammation, 2022
Helin Ceren Köse, Nilüfer Yalçındağ
Adalimumab is a fully humanized monoclonal antibody that blocks the inflammatory effects of TNF-α in various inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn disease. It has been approved by the European Medicines Agency and the U.S. Food and Drug Administration for noninfectious nonanterior uveitis and is considered as a first-line therapy when a therapeutic approach with TNF-α inhibitors for treatment of immune-mediated uveitis has been chosen.27,28 Previous reports have shown that adalimumab is effective in maintaining remission in Behçet uveitis.27–29 Takase et al. reported that switching to adalimumab maintained the remission and prevented ocular relapses in patients with Behçet uveitis. They suggested that adalimumab may be a safe and effective therapeutic option in patients who have an attenuated response or hypersensitivity to IFX.30 Olivieri et al. suggested that patients with Behçet disease showing a limited response or adverse effects to IFX may successfully be treated with adalimumab, regardless of the reason for switching.31 In our study, two patients with ocular attacks after cessation of IFX were switched to adalimumab treatment. Previous studies showed that, adalimumab has especially been used in patients who had an insufficient response or did not tolerate IFX.29–32 Additionally, since adalimumab is a fully recombinant human IgG1 monoclonal antibody specific for human TNF-α; it is less immunogenic than IFX with lower risk of loss of efficacy.
Acute severe attacks of ulcerative colitis in a population-based cohort: epidemiology, treatment and outcome
Published in Scandinavian Journal of Gastroenterology, 2020
Anders Rönnblom, Urban Karlbom
The majority of patients (46 of all 64 severe attacks) were treated with intravenous steroids; the most frequently used dose was betamethasone 8 mg twice daily. In case of insufficient effect of steroids, infliximab was used as rescue therapy. Thirteen episodes of ASUC were treated with infliximab. Three of these with three injections during eight weeks, three episodes were treated with two injections and seven with a single injection. Two patients were treated with adalimumab. One of these was an 11 year old girl that earlier had used infliximab with good effect but she suffered a loss of response. Her severe attack was treated with adalimumab and peroral steroids. The other patient was treated with adalimumab 40 mg each other week, and when her disease deteriorated, she was successfully treated with betamethasone iv and doubling of the biological drug. Roughly, a third of those that suffered from an ASUC without surgery, was thereafter treated with an immunomodulator (see Table 2).