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Bioresponsive Hydrogels for Controlled Drug Delivery
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Tamgue Serges William, Dipali Talele, Deepa H. Patel
The biological agent may be biomolecules (sugars, proteins, nucleic acid, and enzymes), small molecules such as metabolites and peptides or even whole cells such as endothelial cells. Other stimuli include pH variation, temperature, ionic strength, solvent polarity, light, and electric/magnetic field [23].
Clinical Trial Design and Concepts Specific for Biologic Agents in the Treatment of Rheumatic Diseases
Published in Thomas F. Kresina, Monoclonal Antibodies, Cytokines, and Arthritis, 2020
Joint counts, scores, physician assessment, patient assessment, erythrocyte sedimentation rate (ESR), and morning stiffness are universally employed measures. However, significant changes in any of these parameters may not be observable in early clinical trials. Even in long-term studies, controversy exists regarding the utility of ESR, rheumatoid factor, or C-reactive protein (CRP) measurements. The rational study of a new biologic agent in autoimmune disease may require that patients undergo multiple immune function assays on a regular basis. Measuring a variety of biologic markers can be methodologically difficult, and the amount of blood drawn on a regular basis will be carefully monitored by current Investigational Review Board practices. Further, most rheumatologists believe either a health status questionnaire or a functional measurement is important, even if such measures have not been utilized in the approval process of traditional DMARDs (3-7). Pilot studies of new agents may not demonstrate significant change in the traditional clinical outcome measurements. Since no biologic marker has yet been demonstrated to correlate with clinical outcome, it is important to consider a variety of potential leading indicators which could then be standardized for Phase HI studies (Fig. 6).
Biologics in allergic disease
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Tara V. Saco, Farnaz Tabatabaian
All monoclonal biologics approved to date target Th2 asthma. Biomarkers used to identify Th2 asthma include fractional exhaled nitric oxide (FeNO), peripheral eosinophilia, blood periostin level, and presence of allergen-specific IgE. Poorly controlled asthma with recurrent exacerbations is associated with increased blood or sputum eosinophils. It is challenging clinically to measure sputum eosinophils. However, obtaining blood eosinophils is relatively simple. Epithelial cells lining the alveoli express high quantity of inducible nitric oxide synthase (iNOS). IL-4 and -13 upregulate the expression of iNOS and hence the production of nitric oxide (NO) [34,35]. Elevated FeNO is a noninvasive biomarker for T2 inflammation. Periostin is increased in the presence of IL-13 [15]. The clinical use of these biomarkers is an indication of upregulation of Th2 inflammatory mediators and possible responsiveness to these biologic agents. There are no head-to-head trials comparing these agents. Factors that may play a role in selecting a biologic agent include ease of therapy, route and frequency of the medication, out-of-pocket cost and confounding atopic comorbidities, such as atopic dermatitis, nasal polyps, food allergy, and allergic rhinoconjunctivitis.
Risk of infections in psoriasis: assessment and challenges in daily management
Published in Expert Review of Clinical Immunology, 2021
Clara De Simone, Maria Concetta Fargnoli, Paolo Amerio, Luca Bianchi, Maria Esposito, Federico Pirro, Concetta Potenza, Federica Ricceri, Franco Rongioletti, Luca Stingeni, Francesca Prignano
Based on analysis of data from Spain and Israel on 17,739 patients, it was concluded that anti-TNF agents were not associated with an increased risk of serious infections compared to non-biologic systemic therapy [29]. In an analysis of insurance data in 2017, Dobry et al. reported that the risk for serious infections in patients receiving biologics was higher compared with patients receiving a non-biologic agent (adjusted HR, 1.31; 95% CI, 1.02–1.68), with the highest risk for skin and soft tissue infections and meningitis [30]. In a cross-sectional study of hospitalized patients in the US, patients with psoriasis had increased risk of several serious infections, which included methicillin-resistant S. aureus, cellulitis, herpes simplex virus, meningitis, and encephalitis, as well as TB [22]. Similar findings were also noted by Rademaker et al., who reported an increased risk of infection with β-hemolytic streptococci, S. aureus, Porphyromonas gingivalis, Candida, Chlamydia, HIV, and HCV. Moreover, the risk of serious infections was increased in patients on immunomodulating therapy [18]. Notwithstanding, real-life data on psoriasis therapy with biologics and small molecules and risk of infections is limited, lacking the etiology of infections and sometimes providing conflicting evidence.
Safety evaluation of emicizumab prophylaxis in individuals with haemophilia A
Published in Expert Opinion on Drug Safety, 2021
Cassandra P. Wang, Guy Young, Courtney D. Thornburg
The association between the formation of ADAs to biologic agents due to induction of the humoral immune response has been well established in the literature, with the recent emergence of oncologic therapeutic agents highlighting the topic of immunogenicity and its impact on treatment efficacy and safety [45,46]. ADAs can alter the pharmacokinetic profile of biologic agents by binding to the drug, therefore inhibiting its function or accelerating its clearance from the body [47]. Specifically, neutralizing antibodies bind to selective sites of the biologic agent to prevent targeting, with the potential to reduce the drug’s efficacy in the setting of high titers and high-affinity ADAs. Along with its impact on efficacy and pharmacokinetics, ADAs are also associated with immune-mediated toxicity known as infusion-related reactions. Side effects include IgE-mediated hypersensitivity reactions [48] and activation of antibody-dependent cell-mediated toxicity caused by IgG-mediated reactions, which can occur shortly after the infusion of the drug and manifest in a variety of clinical symptoms resembling anaphylaxis [47].
Immunohistochemical evaluation of the prognostic and predictive power of epidermal growth factor receptor ligand levels in patients with metastatic colorectal cancer
Published in Growth Factors, 2020
Siavash Foroughi, Ryan A. Hutchinson, Hui-li Wong, Michael Christie, Ahida Batrouney, Rachel Wong, Margaret Lee, Jeanne Tie, Antony Wilks Burgess, Peter Gibbs
This was a retrospective analysis of mCRC patients with KRAS wild-type tumours who all had initially received first line, palliative intent, oxaliplatin- or irinotecan-based combination chemotherapy with a fluoropyrimidine backbone. Patients may also have received a biologic agent (bevacizumab, cetuximab or panitumumab) during their treatment course. Eligible patients were selected from the Australian Comprehensive Cancer Outcomes and Research Database for Colorectal Cancer (ACCORD-CRC) (Kosmider et al. 2008) and the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) (Field et al. 2013) registries. ACCORD-CRC, and TRACC are prospective multicenter registries enrolling consecutive patients with mCRC from participating centres across Australia. These registries capture comprehensive clinicopathologic, treatment and outcome data, which were extracted for analysis in this study.