Anti-interleukin-17 therapies for moderate/severe psoriasis in clinical practice: effectiveness, safety and association with clinical patient factors.

OBJECTIVES: Interleukin-17 (IL-17) contributes to the pathogenesis of psoriasis. Secukinumab, ixekizumab, and brodalumab are monoclonal antibodies anti-IL-17 antibodies, approved for the treatment of moderate/severe plaque psoriasis.The aim of the study was to describe the effectiveness and safety of anti-IL-17 agents in moderate/severe plaque psoriasis in clinical practice. We also analysed anti-IL-17 therapies' survival, dose adjustment, and clinical patients' factors associated with their effectiveness and safety. METHODS: A retrospective, longitudinal study was conducted at a tertiary hospital. We included patients with moderate/severe psoriasis treated with anti-IL-17 agents. The effectiveness was evaluated with Psoriasis Area and Severity Index (PASI) score and safety through the adverse drug reactions (ADRs) collected. RESULTS: 38 patients were studied (median age=47.4 years, 71.0% male). The mean number of biological therapies that patients received was 2.6, and anti-IL-17 therapy was the first biological therapy for 36.8% of patients. The median years in treatment were 2.5 (95% CI 1.95 to 2.98) for secukinumab, 1.2 (95% CI 0.36 to 1.47) for ixekizumab, and 0.7 (IQR 0.71) for brodalumab. The median PASI score after 6 months of treatment was 0 (IQR 0) and 85.3% of patients achieved a PASI of 90 (84.0% with secukinumab, 87.5% with ixekizumab, and 100% with brodalumab). Dose adjustment was associated with the line of treatment (p=0.034 for naïve patients), age (p=0.044 for younger patients), and concomitant pathologies (p=0.015 without more diseases).24 patients suffered from ADRs, mainly infections of the upper respiratory tract, and there were no statistically significant differences between the three therapies. CONCLUSIONS: Anti-IL-17 agents constitute an effective treatment for patients with moderate/severe plaque psoriasis and for longer. Dose reductions were associated with fewer lines of treatment, younger patients and absence of concomitant pathologies. ADR were minor and similar among the anti-IL-17.

Recomendaciones para la administración de antineoplásicos e inmunomoduladores orales por sonda enteral en oncohematología / Recommendations for using oral antineoplastic and immunomodulating agents in oncohematology by enteral tube administration

Introducción y objetivo: en los últimos años, el número de fármacos antineoplásicos e inmunomoduladores orales (ANIOS) ha crecido enormemente. Con frecuencia, estos fármacos deben administrarse por sonda enteral (SE) o a pacientes con problemas de deglución, planteando un problema respecto a su manipulación (muchos pertenecen al grupo de medicamentos peligrosos). Además, también pueden presentar interacciones cuando se administran con la nutrición enteral (NE). El objetivo ha sido analizar y actualizar las recomendaciones de administración y manipulación de los ANIOS. Métodos: se creó un Grupo de Trabajo formado por farmacéuticos del Grupo de Farmacia de la Sociedad Española de Nutrición Clínica y Metabolismo (SENPE) y del Grupo de Nutrición Clínica de la Sociedad Española de Farmacia Hospitalaria (SEFH). Se realizó una revisión bibliográfica entre 2015 y 2020 de las condiciones de manipulación y administración de los ANIOS en oncohematología, elaborando una tabla que recoge especialidades farmacéuticas, dosis, presentación, nombre comercial, instrucciones para la administración oral y por SE, interacciones con la NE, precauciones y observaciones para su manipulación y administración. Resultados: se elaboró una tabla con 77 principios activos y 84 formas farmacéuticas, recogiendo recomendaciones e instrucciones para su administración por vía oral, sonda nasogástrica y gastrostomía, para la correcta manipulación y para la administración junto a la NE. Conclusiones: la información sobre cómo administrar y manipular los ANIOS en personas con accesos enterales o problemas de deglución es escasa. Consideramos importante incluir en los estudios poscomercialización una investigación dirigida a responder a estas cuestiones para garantizar una administración segura y eficaz de los medicamentos a estos pacientes (AU)

Introduction and objective: in recent years, the number of oral antineoplastic and immunomodulating drugs in oncohematology has increased enormously. Often, these drugs must be administered to patients with enteral tube feeding or swallowing disorders, which causes safety problems when handling these drugs (many of them are classified as hazardous drugs). In addition, it is important to note that the administration of these drugs can also interact with enteral nutrition (EN). The objective of this study was to review and update the recommendations for the administration and handling of oral antineoplastic and immunomodulating drugs. Methods: a Working Group made up of pharmacists from the Pharmacy Group of The Spanish Society of Clinical Nutrition and Metabolism (SENPE) and the Clinical Nutrition Group of The Spanish Society of Hospital Pharmacy (SEFH) was created. A bibliographic review was carried out between 2015 and 2020 on the administration and handling of oral antineoplastic and immunomodulating drugs in oncohematology. The information about pharmaceutical specialties, dosage, presentation, brand names, instructions for oral or enteral tube administration, interactions with EN, precautions, and remarks for handling and administration was analyzed. Results: a total of 77 active principles and 84 pharmaceutical forms were included. Recommendations and instructions for oral, nasogastric tube, and gastrostomy administration, handling of the antineoplastic and immunomodulating drugs, and interactions with EN were described. Conclusions: the handling and administration information about the oral antineoplastic and immunomodulating drugs currently used in oncohematology for people with enteral accesses or swallowing disorders is limited. It is important to perform post-marketing studies to ensure a safe and effective administration of these drugs (AU)

The use of autologous serum eye drops for the treatment of ocular surface disorders.

OBJECTIVES: To investigate the use of autologous serum (AS) eye drops in patients with ocular surface disorders who were refractory to conventional treatments. METHODS: A retrospective cohort study was conducted at a tertiary care centre. We included patients with a prescription of AS eye drops from December 2006 to January 2016. Electronic prescriptions (Prescriplant) and clinical histories were reviewed. A database with sociodemographic and pharmacotherapheutic variables was created. The efficacy was evaluated subjectively and adverse effects was a measurement of safety. AS eye drops were elaborated, in a laminar flow hood, with the blood samples for a final concentration of 20%. RESULTS: One hundred and seventy-three patients were considered for the study, 78.03% of them female. Their mean age was 63.87 years (SD 16.69). The use of AS eye drops was indicated for several diseases: corneal diseases (corneal ulcer or corneal persistent epithelial defects) (34.32%); Sjögren syndrome (17.16%); dry eye resulting from autoimmune disease (15.38%); and blepharitis/blepharospasm (12.43%). The regular dosage was every 3 or 4 hours (40.46%). 21.97% patients used the AS in one eye only. The mean length of treatment was 2.71 years. All patients, except one, improved their symptoms with the treatment and no one suffered harmful effects. CONCLUSIONS: Numerous national and international guidelines on dry eye treatment have been published, but they differ in dosing, concentration and indication of AS eye drops. Consequently, there is no consensus about the best therapy with AS. In this article we describe the clinical practice of AS eye drops. In the study, indications for AS therapy were mostly: corneal diseases; Sjögren syndrome; and dry eye resulting from autoimmune disease; and blepharitis or blepharospasm. Patients went to the hospital pharmacy to pick up AS eye drops before 90 days, it ensures the stability of eye drops. AS is an effective, safe and well tolerated treatment.

Drug cost avoidance in clinical trials of breast cancer.

BACKGROUND: The objectives of this study were to determine if clinical trials in breast cancer, with an investigational drug, created direct drug cost savings for the healthcare system related to cost avoidance of the best standard of care treatments used in these studies. The aim was to quantify this potential drug cost avoidance. METHODS: We conducted a retrospective observational study of the drug cost avoidance during the study period (2014-2016). We included clinical trials with investigational drug, managed by pharmacy department and provided by the sponsor. The patients included had a therapeutic alternative defined as standard treatment that should have been received in case of not participating in the clinical trial. Direct cost savings, to national healthcare system, associated to clinical trials were calculated. RESULTS: Thirty-seven clinical trials with a total of 89 breast cancer patients were included in the study. A total of 62.2% were phase III and 75.7% belonged to the pharmaceutical industry. They provided a total cost avoidance of 957,246€ (1,130,028$), an average cost avoidance per patient of 10,756€ (12,697$). CONCLUSIONS: Our study suggests that those clinical trials in which investigational drug are provided or refunded by the sponsor provide substantial cost savings. Due to the shortage of published articles that calculate the cost avoided in medication, we cannot compare directly the results obtained in the different institutions.

[Failure mode and effects analysis to improve quality in clinical trials]. / Análisis modal de fallos y efectos para mejorar la calidad en los ensayos clínicos.

INTRODUCTION: The failure mode and effects analysis (FMEA) has been used as a tool in risk management and quality improvement. The objective of this study is to identify the weaknesses in processes in the clinical trials area, of a Pharmacy Department (PD) with great research activity, in order to improve the safety of the usual procedures. METHODS: A multidisciplinary team was created to analyse each of the critical points, identified as possible failure modes, in the development of clinical trial in the PD. For each failure mode, the possible cause and effect were identified, criticality was calculated using the risk priority number and the possible corrective actions were discussed. RESULTS: Six sub-processes were defined in the development of the clinical trials in PD. The FMEA identified 67 failure modes, being the dispensing and prescription/validation sub-processes the most likely to generate errors. All the improvement actions established in the AMFE were implemented in the Clinical Trials area. DISCUSSION: The FMEA is a useful tool in proactive risk management because it allows us to identify where we are making mistakes and analyze the causes that originate them, to prioritize and to adopt solutions to risk reduction. The FMEA improves process safety and quality in PD.

Pharmacotherapy follow-up of key points in the safety of oral antineoplastic agents.

We assessed the impact of a pharmacotherapy follow-up programme on key safety points [adverse events (AE) and drug administration] in outpatients treated with oral antineoplastic agents (OAA). We performed a comparative, interventional, quasi-experimental study of outpatients treated with OAA in a Spanish hospital to compare pre-intervention group patients (not monitored by pharmacists during 2011) with intervention group patients (prospectively monitored by pharmacists during 2013). AE data were collected from medical records. Follow-up was 6 months, and 249 patients were included (pre-intervention, 115; intervention, 134). After the first month, AE were detected in 86.5% of patients in the pre-intervention group and 80.6% of patients in the intervention group, P = 0.096. During the remaining months, 79.0% patients had at least one AE in the pre-intervention group compared with 78.0% in the intervention group, P = 0.431. AE were more prevalent with sorafenib and sunitinib. In total, 173 drug interactions were recorded (pre-intervention, 80; intervention, 93; P = 0.045). Drug interactions were more frequent with erlotinib and gefitinib; food interactions were more common with sorafenib and pazopanib. Our follow-up of cancer outpatients revealed a reduction in severe AE and major drug interactions, thus helping health professionals to monitor the safety of OAA.

Impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome.

WHAT IS KNOWN AND OBJECTIVE: Regular blood transfusions in the management of myelodysplastic syndrome (MDS) often lead to iron overload. The main objective of this study was to evaluate the impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in patients with MDS. Secondary objectives were to describe treatment effectiveness and safety in daily clinical practice. METHODS: A longitudinal, retrospective, observational study was carried out in a university hospital. The inclusion criteria were age over 18 years, MDS diagnosis and treatment with deferasirox for transfusion-dependent iron overload during the period of study (from January 2011 to April 2015). Treatment effectiveness was estimated by serum ferritin (SF), and adherence was measured by medication possession ratio (MPR). Clinically relevant analytical alterations during the treatment and reasons for treatment discontinuation were also assessed. RESULTS: Thirty-five patients were included in the study. Median SF at baseline was 1636 µg/L, and it decreased to 1399 µg/L during follow-up. The median adherence rate was 92%, although only 54·8% of the patients maintained deferasirox adherence ≥90% during the whole duration of treatment. Adherence rate was inversely correlated to SF (r = -0·288, P = 0·004). The median (p25, p75) duration of treatment was 11 (3·0, 37·8) months. The most common reasons for treatment discontinuation were renal toxicity (35%) and patient's death (25%). WHAT IS NEW AND CONCLUSION: Deferasirox's effectiveness, measured by the decrease in SF, was significantly better in adherent patients. The most frequent reason for treatment discontinuation was renal toxicity. Developing strategies to improve deferasirox treatment adherence and monitoring renal function in those patients should be key points in pharmaceutical care.

Dose Modification in Biologic Therapy for Moderate to Severe Psoriasis: A Descriptive Analysis in a Clinical Practice Setting.

INTRODUCTION: In biologic therapy, dose modification in carefully selected patients when psoriasis is in remission could reduce treatment costs and the risks associated with drug exposure. MATERIAL AND METHODS: Observational, descriptive, crosssectional study, performed in January 2014, of 112 patients with moderate to severe psoriasis who had been on biologic therapy for at least 6 months. The therapeutic objective in all cases was to achieve and maintain a 75% reduction in Psoriasis Area and Severity Index (PASI 75). All the patients had started treatment with the standard regimen. During treatment, the dose had been reduced in patients who achieved the therapeutic objective and escalated in those who failed to respond adequately to standard doses. RESULTS: At the time of the study, 42.9% of the patients were receiving the standard dose, 50% were on a reduced dose, and 7.1% were on an escalated regimen. The agent with which the dose was most often reduced was adalimumab (57.7%), and the agents with which therapy was most often escalated were ustekinumab (17.9%) and infliximab (12.5%). Patients who received reduced doses had significantly longer-standing disease (P=.049) and longer treatment duration with the same biologic agent (P=.009). In the group that did not fulfill the criteria for dose reduction, the proportion of patients with psoriatic arthritis was significantly higher (P=.023). Cost savings were as follows: 21.5% with adalimumab, 13.8% with etanercept, .9% with ustekinumab, and .55% with infliximab. CONCLUSIONS: Patients with longer-standing disease and longer treatment duration with the same biologic agent were significantly more likely to be candidates for dose reduction. The proportion of patients with psoriatic arthritis was greater in the group of patients who did not fulfill the conditions for dose reduction. The overall cost saving achieved using the dose modification algorithm described in this study was 13%. Controlled studies are needed to define the profile of the patients best suited for dose reduction strategies without loss of treatment efficacy.

[Evaluation of drug administration through enteral feeding tubes in hospitalized patients]. / Evaluación de las prácticas de administración de fármacos por sonda nasoentérica y enterostomía en pacientes hospitalizados.

OBJECTIVE: To describe the administration of drugs through nasogastric tubes by the nursing staff of a tertiary hospital and to identify the most common administration errors. METHODS: An observational study was carried out between November of 2010 and March of 2011. The study population was the nursing staff of the hospital. A questionnaire was created asking about the daily practice of drugs administration through the nasogastric tube; a score was assigned to each question. A document on correct administration techniques of drugs through the nasogastric tube was elaborated, which served for the comparison of the answers obtained. RESULTS: A total of 162 surveys were answered. Most of the staff (44.5%) had a deficient knowledge on the proper administration techniques. 69.7% of the staff stated to have grinded some time a tablet with enteric coverage, and 66.2% a tablet with modified release. A significant lower number of perceived obstructions per month was obtained in those nurses with higher degree of knowledge, in those consulting the Pharmacy Department when they had doubts, and in those never having grinded a tablet with enteric coverage of modified release. CONCLUSIONS: It is observed that the knowledge on proper administration of drugs through the nasogastric tube by the nursing staff is deficient; therefore, it would be convenient to carry out specific training courses as well as a closer collaboration between the Pharmacy department and the Nursing units.