Manuel Busto-Iglesias’s research while affiliated with University of Santiago de Compostela and other places

Background and Importance In patients with NSCLC and programmed death ligand-1 (PD-L1) expression ≥50%, pembrolizumab as first-line treatment has shown an increase in survival over platinum-based chemotherapy. To date, it is not known whether higher PD-L1 expression is associated with longer survival. Aim and Objectives The aim of this study is to evaluate the impact of PD-L1 expression levels on progression free survival (PFS) and overall survival (OS), in patients receiving first-line pembrolizumab treatment for NSCLC and its association to histologic type. Material and Methods A retrospective analysis of patients with metastatic NSCLC and PD-L1 expression level of ≥50%, who were treated with pembrolizumab monotherapy as first-line therapy in our centre from January 2020 to January 2022 was carried out. The difference in response between the histologic type of NSCLC (adenocarcinoma and non-adenocarcinoma), and efficacy of pembrolizumab by level of PD-L1 expression was studied. ROC curve was used to evaluate the optimal PD-L1 cut-off point to identify a greater possibility of response. Event-time distributions were estimated using Kaplan–Meier methodology. Log-rank tests were used to test for differences in event-time distributions. All p-values are 2-sided and CIs are at the 95% level, with significance pre-defined to be at the 0.05 level. Results 49 patients were included in the study. 36 patients (73.5%) had adenocarcinoma histology, 10 (20.4%) epidermoid, and 3 (6.1%) other. A cut-off of 80% for PD-L1 expression was established. 40 (81.6%) had PD-L1 expression <80% and 9 (18.4%) ≥80%. Median PFS was 14.7 months (95% CI: 7.0-15.1) in patients with PD-L1 <80% and 25.8 months (95% CI: not reached) in patients with PD-L1 ≥80% (p=0.017). No differences were found in OS. Patients with adenocarcinoma and PD-L1 expression ≥80% obtained better results in in terms of PFS: 19.3 months (95% CI: not reached, p=0.031). Conclusion and Relevance Statistically significant differences in PFS but not OS were found in patients with NSCLC and PD-L1 ≥80% expression. Adenocarcinoma with PD-L1 ≥80% seem to benefit the most from pembrolizumab treatment than other NSCLC histologies. These findings could have implications for treatment selection based in NSCLC histology. Future research is needed. References and/or Acknowledgements 1. Aguilar EJ et al., Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. AnnOncol.2019oct1;30(10):1653-1659. Conflict of Interest No conflict of interest

Biological drugs, especially those targeting anti-tumour necrosis factor α (TNFα) molecule, have revolutionized the treatment of patients with non-infectious uveitis (NIU), a sight-threatening condition characterized by ocular inflammation that can lead to severe vision threatening and blindness. Adalimumab (ADA) and infliximab (IFX), the most widely used anti-TNFα drugs, have led to greater clinical benefits, but a significant fraction of patients with NIU do not respond to these drugs. The therapeutic outcome is closely related to systemic drug levels, which are influenced by several factors such as immunogenicity, concomitant treatment with immunomodulators, and genetic factors. Therapeutic drug monitoring (TDM) of drug and anti-drug antibody (ADAbs) levels is emerging as a resource to optimise biologic therapy by personalising treatment to bring and maintain drug concentration within the therapeutic range, especially in those patients where a clinical response is less than expected. Furthermore, some studies have described different genetic polymorphisms that may act as predictors of response to treatment with anti-TNFα agents in immune-mediated diseases and could be useful in personalising biologic treatment selection. This review is a compilation of the published evidence in NIU and in other immune-mediated diseases that support the usefulness of TDM and pharmacogenetics as a tool to guide clinicians’ treatment decisions leading to better clinical outcomes. In addition, findings from preclinical and clinical studies, assessing the safety and efficacy of intravitreal administration of anti-TNFα agents in NIU are discussed.

Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19; EudraCT number: 2020-001760-29).

Inhaled administration of ethanol in the early stages of COVID‐19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS‐GC‐MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early‐stage COVID‐19 patients, which is currently in the recruitment phase (ALCOVID‐19; EudraCT number: 2020‐001760‐29).

Background and importance Tacrolimus is an immunosuppressant with many potential uses in ophthalmic diseases. It is an inhibitor of calcineurin phosphatases, which suppress the first phase of T cell activation and leads to a decrease in inflammatory activity. There are no commercialised eye drops in Spain so its formulation as a pharmaceutical compound has to be done by the hospital pharmacy services. Aim and objectives To evaluate the use, tolerance and adherence of 0.03% tacrolimus eye drops as a pharmaceutical compound. Material and methods A retrospective observational study was conducted in patients treated with 0.03% tacrolimus eye drops from January 2017 to March 2020. The eye drops were prepared and dispensed by the hospital pharmacy service. For the preparation, 0.6 mL of intravenous Prograf 5 mg/mL were diluted with Liquifilm to a final volume of 10 mL.Demographic (sex and age) and clinical data (diagnosis, duration, adherence and tolerance) were recorded using electronic prescription and electronic medical records. Adherence was measured using registered dispensations as well as by follow-up controls by an ophthalmologist. We classified as the most compliant patients those with no delay in dispensation times in the pharmacist consultation. Results 54 patients (57% men) with a mean age of 32±21 years used tacrolimus eye drops during the study period. Tacrolimus eye drops were used for the treatment of immune mediated ophthalmic inflammatory diseases in 61.8% of patients, of whom 49.1% were for atopic or vernal keratoconjunctivitis. 20.0% of the total number of patients used the eye drops for hyperaemia of unknown cause,12.7% were used for dry eye and the remaining 5.4% for the treatment of graft rejections.Mean duration of treatment was 1.8±1.0 years. Tolerance was generally good. Only 24.07% of patients presented with itching, and 2 patients (3.70%) had palpebral dermatitis and miosis. 50% of patients were highly compliant (having no delay in dispensations), 38.89% had delayed dispensing at least once, 9.26% had delayed dispensing at least twice and 1.85% had irregular dispensations. Conclusion and relevance 0.03% tacrolimus eye drops were used primarily for the treatment of vernal or atopic keratoconjunctivitis but they have wide potential uses in ophthalmology diseases. The formulation was well tolerated by most of patients and adherence was generally correct, as measured by the pharmacist consultations. Conflict of interest No conflict of interest

The health crisis resulting from the rapid spread of SARS-CoV-2 worlwide, added to the low evidence of currently used treatments has led to the development of a large number of clinical trials (CT) and observational studies. Likewise, important measures have been adopted in healthcare and research centers aimed at halting the pandemic as soon as possible. The objective of this study is to gather the main aspects of the clinical research studies undertaken by the Departments of Hospital Pharmacy (DHP) of Spain during the COVID-19 crisis. The decision of the Spanish Society of Hospital Pharmacy (SEFH) to sponsor CTs made it possible that 13% of DHP had been led at least one CT. The Spanish Agency for Medicines and Medical Devices (AEMPS), in coordination with Institutional Review Boards, has adopted a fast-track review procedure to accelerate authorizations for CTs related to the treatment or prevention of COVID-19. There have also been numerous public and private calls for financing research projects aimed at contributing to the fight against this virus. Despite the pandemic, actions have been taken to continue ongoing CTs and studies while the safety and well-being of patients are guaranteed. More specifically, the AEMPS and the European Medicines Agency (EMA) have issued guidelines that incorporate changes to CT protocols that will have to be applied until the pandemic is over. In this health emergency, the scientific community has found itself in a race against time to generate evidence. It is at this moment that hospital pharmacists emerge as key players in clinical research and are contributing to a rational, effective and safe healthcare decision-making.

Background and importance Long acting injectable antipsychotics have emerged to improve adherence and reduce the risk of relapse in patients with psychiatric disorders. Aim and objectives The aim was to evaluate the maintenance rate of long acting injectable antipsychotics in real life. Material and methods A retrospective observational study was conducted from April 2017 to April 2019 in outpatients in mental health units who initiated long acting injectable antipsychotic treatment (monthly aripiprazole 400 mg (MA), monthly paliperidone 150 mg (MP) or quarterly paliperidone 525 mg (QP)) between April and September 2017. Anthropometric data, injectable antipsychotic treatment and psychiatric diagnoses were collected. Active treatments, discontinuations and changes in drugs, formulations (monthly/quarterly) and doses were recorded in April 2018 and April 2019. Results A total of 113 patients were included. Treatments were 46.0% (52) MA, 40.7% (46) MP and 13.3% (15) QP. Average ages (MA, MP, QP) were 41.75±12.8, 47.70±14.9 and 44.13±7.1 years, respectively, and the number of men were 56.69%, 76.09% and 93.33%, respectively. Diagnoses (MA, MP, QP) were paranoid schizophrenia in 55.77%, 54.35% and 53.33%, respectively; substance abuse related disorder in 7.69%, 4.35% and 6.67%, respectively; simple schizophrenia in 17.31%, 10.87% and 13.33%, respectively; intellectual disability in 3.85%, 4.35% and 0%, respectively; personality disorder in 1.92%, 4.35% and 0%, respectively; and other in 13.46%, 21.73% and 26.67%, respectively.In April 2018, 90.38% (47) of MA patients maintained treatment, while 9.62% (5) discontinued treatment. A year later, 76.92% (40) maintained treatment, 5.77% (3) changed doses and 17.31% (9) had discontinued their treatment. For MP, 58.70% (27) continued with treatment in the first year, 19.57% (9) changed to QP, 6.51% (3) changed doses but maintained the monthly administration and 15.22% (7) interrupted treatment. In the second year, 50.00% (23) maintained treatment, 17.39% (8) changed to QP and 10.87% (5) changed dose. Treatment was interrupted in 21.74% (10) of patients at the end of the study. For the QP group, 53.33% (8) maintained treatment in the first year while 26.67% (4) required a change to MP and 20.00% (3) interrupted treatment. At the end of the study, 40.00% (6) maintained treatment, 26.67% (4) continued with MP, 6.66% (1) changed to MA and 26.67% (4) discontinued treatment. Conclusion and relevance A good maintenance rate was observed with MA and MP over 2 years. In contrast, half of the patients receiving QP had to interrupt their treatment during the first year due to a short acting duration. Almost a third of QP patients had to restart treatment with MP. In conclusion, the maintenance rate was higher in monthly presentations than in the quarterly presentation. References and/or acknowledgements N/ANo conflict of interest.