Biosimilar epoetin for cancer and chemotherapy-induced anaemia in the US

Biosimilars are biological drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety and efficacy. Biosimilar epoetin received US Food and Drug Administration (FDA) approval in 2018 [1]. The manufacturer received an FDA non-approval letter in 2017, despite receiving a favourable review by the FDA’s Oncologic Drugs Advisory Committee (ODAC) and an FDA non-approval letter in 2015 for an earlier formulation.

Recombinant Production of IL-1Ra in Fusion to Albumin Binding Domain for Its Extended Half-Life

Background: Anakinra, a FDA approved biological drug for Rheumatoid Arthritis, must be injected daily due to its short Half-life, leads to the lower patient compliance. So, the aim of this study was to produce IL-1Ra in fusing to albumin binding domain to extend its half-life and evaluate its biological effects.Methods and Results: The expression of IL-1Ra-ABD was performed in E. coli in fusing to intein1 of pTWIN1 in soluble and purified. The affinity of IL-1Ra-ABD to HSA was determined on Native-PAGE and its release percent toward time was determined. Finally, MTT assay was used to determine the antagonizing properties of recombinant IL-1Ra-ABD against IL-1β, on A375 cells. the expression induction of intein1-IL-1Ra-ABD using 0.1mM of IPTG at 15°C, and its cleavage represented a band approximately in 50 and 23 kDa respectively. Native-PAGE results showed that about 78% of IL-1Ra-ABD attached to the HSA after 2 hours of incubation, and MTT assay results showed no significant differences between the effects of our recombinant protein and native IL-1Ra.Conclusion: the production of soluble IL-1Ra-ABD with similar antagonizing effects to IL-1Ra was successfully performed. IL-1Ra-ABD showed suitable interaction with HSA and release over the time. However, pharmacokinetics and furthur biological evaluations are required.

Spondyloarthritis and Strength Training: A 4-Year Report

Peripheral spondyloarthritis (SpA) has predominant peripheral (arthritis, enthesitis, or dactylitis) involvement. The severity of the symptoms can have a significant impact on the quality of life. There is no therapeutic gold standard, and physical exercise, with the opposition of resistance, remains controversial. Herein, we report the case of a woman who, at the age of 50, comes to our center with evident motor difficulties. She was previously diagnosed with SpA and was in therapy with a biological drug (adalimumab) for over one year. The training program and the nutritional intervention plan improved her condition, as pointed out by WOMAC, SQS, RAD-36 questionnaire, and BIA analysis, suspending biological therapy for almost two years. During this period, she achieved in sequence: (i) the Italian master deadlift championship, and (ii) the Italian master powerlifting championship, both for two consecutive years.

Selection of a genetically engineered biological drug for ankylosing spondylitis with extra-skeletal manifestations

Ankylosing spondylitis (AS) is a chronic, gradually progressive inflammatory disease of the spine, which in some patients can occur simultaneously with lesions of entheses and peripheral joints, and in some cases the eyes (uveitis) and the aortic root (aortitis). In more than 90% of cases, the genetic marker HLA-B27 is detected. This article presents a clinical case of ankylosing spondylitis in a man who received regular GEBD therapy, against the background of which uveitis recurred. After changing the drug, the inflammatory diseases of the eyes did not recur, and clinical remission was achieved.

Impact of Interferons and Biological Drug Inhibitors of IL-2 and IL-6 on Small-Molecule Drug Metabolism Through the Cytochrome P450 System

Objective: Assess the impact of interferons and interleukin (IL)-2 and IL-6 inhibitors on cytochrome P450 (CYP) drug metabolism in human subjects. Data Sources: PubMed search from 1980 to March 31, 2021, limited to human subjects and English language via search strategy: (biological drug names) [AND] (cytochrome [OR] CYP metabolism). Study Selection and Data Extraction: Narrative review of human studies assessing biological drugs in select classes that affect CYP drug metabolism. Data Synthesis: Exogenous interferons suppress CYP1A2 (theophylline, caffeine, antipyrone) clearance by 20% to 49% in patients; have minimal impact on CYP3A4 (midazolam and dapsone), CYP2C9 (tolbutamide), or CYP2C19 (mephenytoin) metabolism; and increase CYP2D6 (debrisoquine, dextromethorphan) metabolism. Biological IL-2 inhibitors (basiliximab, daclizumab) have no effect on metabolism via CYP1A2 (caffeine), CYP2C9 (s-warfarin), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam, tacrolimus) but may enhance CYP3A4 (cyclosporin) metabolism over time. IL-6 inhibitors (sirukumab, tocilizumab, sarilumab) significantly enhance metabolism via CYP2C9 (s-warfarin), CYP2C19 (omeprazole), and CYP3A4 (simvastatin, midazolam) and reduce metabolism via CYP1A2 (caffeine). Relevance to Patient Care and Clinical Practice: Patients using interferons, IL-2, or IL-6 blocking drugs at steady state with CYP substrates could have altered drug metabolism and experience adverse events. With interferons and biological anti-inflammatory drugs, some isoenzymes will be inhibited, whereas others will be enhanced, and the magnitude of the effect can sometimes be significant. In clinical practice, clinicians may consider these metabolic changes as an additive effect to a patient’s entire disease and medication profile when determining risk/benefit of treatment. Conclusions: Interferon therapy or inflammatory suppression via IL-2 or IL-6 can alter steady-state concentrations of CYP-metabolized small-molecule drugs.