Faes Farma (Spain)

Abstract Background Mesalazine (msz) is commonly used alongside advanced therapies in ulcerative colitis (UC), but its precise effects on efficacy and safety are not fully defined. This meta-analysis indirectly evaluates the impact of concomitant msz use on clinical and endoscopic outcomes and safety profiles in adults with moderate-to-severe UC treated with approved biological agents and small molecules. Methods A meta-analysis of RCTs including approved biological agents (Adalimumab, Infliximab, Golimumab, Mirikizumab, Guselkumab, Ozanimod, Etrasimod, Ustekinumab) and small molecules (Tofacitinib, Upadacitinib) in UC patients reporting concomitant msz use was conducted through a search of four databases. Available data on clinical remission, endoscopic remission, mucosal healing and adverse events were extracted. Msz co-therapy prevalence was categorized using the median concomitant use across datasets as the baseline threshold. Studies were stratified into ‘High’ and ‘Low’ prevalence groups based on this median. Pooled proportions for each outcome and subgroup were estimated, with between-group differences tested by two-tailed z-tests. Separate analyses were performed for induction and maintenance phases, including only approved UC treatment doses. Meta-regression assessed correlations between concomitant mesalazine prevalence and treatment outcomes. Results 32 Phase II and III RCTs were included. No statistically significant differences were shown during the induction phase (Table1). In the maintenance phase, the subgroup with a higher prevalence of msz use showed significantly greater mucosal healing than the low-prevalence group (45.0%[95%CI,32.0%–58.0%] vs. 29.0%[95%CI,21.0%–39.0%]), with a borderline positive correlation in meta-regression (r = 0.503,p=0.067) (Figure1). Conversely, infection rates were significantly higher among patients with higher msz prevalence during maintenance therapy (23.0% [95%CI,0.9%–47.0%] vs. 0.1%[95%CI,0.0%–12.0%]), supported by a significant meta-regression correlation (r = 0.396,p=0.015). No difference was found in serious infection rates between the high and low prevalence groups (p > 0.05). No other efficacy nor safety outcomes showed significant differences between groups. Conclusion The concomitant use of msz and advanced therapies is associated with improved mucosal healing during maintenance therapy for UC, suggesting a potential synergistic effect in the long term. Future prospective studies incorporating histologic outcomes are warranted to elucidate the mechanistic contribution of msz in combination regimens. Conflict of interest: Rodríguez-Lago, Iago: Financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma. Research support from AbbVie. Supported by a research grant from Gobierno Vasco-Eusko Jaurlaritza (Grant No 2020111061 and 2023222006). D’Amico, Ferdinando: Grant: ECCO fellowship grant 2020 ECCO grant 2021 Personal Fees: F D’Amico has served as a speaker for Abbvie, Alfasigma, Ferring, Lilly, Sandoz, Janssen, Fresenius Kabi, Galapagos, Giuliani, MSD, Pfizer, Takeda, Tillotts, and Omega Pharma he also served as an advisory board member for Abbvie, AnaptysBio, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Takeda, and Nestlè. Bamias, Giorgos: Grants: Grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis Consulting Fees and Speaker Honoraria: AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Faran, Ferring, Galenica, Genesis Pharma, J&ampJ, Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Shattuck Labs, Takeda, Vianex Mrs. Miranda Azpiazu, Patricia: Employed at Faes Farma S.A Barreiro-de Acosta, Manuel: MBA has been speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Alphasigma, Lilly, Pfizer, Sandoz, Biocon, Abivax, Fresenius, Faes Farma, Ferring, Tillots, Chiesi, Adacyte, Diasorin, Oncostellae and SunRock.

Karsten Weller is or recently was a speaker and/or advisor for Dr. Pfleger, Uriach, UCB, Moxie and Novartis. Martin Church has been a speaker or consultant for Almirall, FAES FARMA S.A., Menarini, Moxie, MSD, Novartis, UCB Pharma, Sanofi-Aventis and Uriach. Tomasz Hawro has no conflict of interest. Sabine Altrichter has conducted studies for Allakos, GSK, Moxie and Novartis. Luis Labega is a member of the medical department of FAES FARMA S.A. Markus Magerl is or recently was a speaker and/or advisor for Moxie and Novartis. Martin Metz has been a speaker and/or consultant for Bayer Pharma, Moxie, Novartis and Uriach. Torsten Zuberbier has consulted and had research grants and/or honoraria from AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bayer Health Care, Bencard, Berlin Chemie, FAES FARMA S.A, HAL, Henkel, Kryolan, Leti, L'Oreal, Meda, Menarini, Merck, MSD, Novartis, Pfizer, Sanofi, Stallergenes, Takeda, Teva and UCB. Marcus Maurer is or recently was a speaker and/or advisor for and/or has received research funding from Allakos, Aralez, Genentech, GSK, Menarini, Merckle Recordati, Moxie, Novartis, Sanofi, MSD and Uriach.

The discovery that the cells communicate through emission of vesicles has opened new opportunities for better understanding of physiological and pathological mechanisms. This discovery also provides a novel source for non-invasive disease biomarker research. Our group has previously reported that hepatocytes release extracellular vesicles with protein content reflecting the cell-type of origin. Here, we show that the extracellular vesicles released by hepatocytes also carry RNA. We report the messenger RNA composition of extracellular vesicles released in two non-tumoral hepatic models: primary culture of rat hepatocytes and a progenitor cell line obtained from a mouse foetal liver. We describe different subpopulations of extracellular vesicles with different densities and protein and RNA content. We also show that the RNA cargo of extracellular vesicles released by primary hepatocytes can be transferred to rat liver stellate-like cells and promote their activation. Finally, we provide in vitro and in vivo evidence that liver-damaging drugs galactosamine, acetaminophen, and diclofenac modify the RNA content of these vesicles. To summarize, we show that the extracellular vesicles secreted by hepatocytes contain various RNAs. These vesicles, likely to be involved in the activation of stellate cells, might become a new source for non-invasive identification of the liver toxicity markers.

This study evaluated the tissue distribution of total radioactivity in male albino, male pigmented, and time-mated female albino rats after oral administration of a single dose of [14C]-bilastine (20 mg/kg). Although only 1 animal was analyzed at each time point, there were apparent differences in bilastine distribution. Radioactivity was distributed to only a few tissues at low levels in male rats, whereas distribution was more extensive and at higher levels in female rats. This may be a simple sex-related difference. In each group and at each time point, concentrations of radioactivity were high in the liver and kidney, reflecting the role of these organs in the elimination process. In male albino rats, no radioactivity was measurable by 72 hours postdose. In male pigmented rats, only the eye and uveal tract had measurable levels of radioactivity at 24 hours. Measureable levels of radioactivity were retained in these tissues at the final sampling time point (336 hours postdose), indicating a degree of melanin-associated binding. In time-mated female rats, but not in albino or pigmented male rats, there was evidence of low-level passage of radioactivity across the placental barrier into fetal tissues as well as low-level transfer of radioactivity into the brain.

Background:The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines development group examined the properties of oral H1-antihistamines and made proposals about an ‘optimal’ drug. Several criteria should be met by oral H1-antihistamines in terms of their pharmacological, and clinical efficacy and safety profiles.Objective:Bilastine, a new H1-antihistamine, has been approved in 28 European countries for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. To determine its potential place in therapy in the treatment of allergic rhinitis, this manuscript examines whether bilastine meets the criteria defined in the European Academy of Allergy and Clinical Immunology (EAACI)/ARIA proposals for oral H1-antihistamines.Methods:The optimal properties of oral H1-antihistamines and current ARIA recommendations for their use in allergic rhinitis are presented, as well as relevant pharmacological and clinical data for bilastine obtained from the published literature that specifically address the defined criteria.Results:Bilastine is a potent inhibitor of the histamine H1 receptor. Data from preclinical studies have confirmed its selectivity for the histamine H1 receptor over other receptors, and demonstrated antihistaminic properties in vitro and in vivo. Bilastine does not interfere with the cytochrome P450 system and is devoid of cardiac side effects. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. In large pivotal randomized, placebo-controlled trials (RCTs), bilastine had a favourable safety profile. Bilastine 20 mg once daily improved all nasal and ocular symptoms of allergic rhinitis with greater efficacy than placebo and comparable to that of cetirizine and desloratadine. Moreover, bilastine was shown to improve quality of life, an important outcome of RCTs in allergic diseases. There were no significant changes in laboratory tests, electrocardiograms or vital signs. A potential limitation of this assessment of bilastine is that it is a literature-based review and the findings are dependent upon the quality of the published evidence.Conclusions:Bilastine meets current EAACI/ARIA criteria for medications used in the treatment of allergic rhinitis.

Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two participants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.

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The tigecycline susceptibility of six different Enterobacteriaceae strains with reported high tigecycline MICs was determined in quintuplicate by four methodologies using Mueller-Hinton agar and broth from six manufacturers. The MICs determined by Etest were a >or=1-fold dilution lower than those determined by broth microdilution and agar dilution, with the highest modal values given by agar dilution. The highest modal MICs were obtained using Oxoid medium, and the lowest inhibition zone values (disc diffusion) were obtained using Oxoid and bioMérieux media. The lowest MICs were obtained by Etest using Difco or Merck media.