Retrospective study of apremilast drug survival in psoriasis patients in a daily practice setting: A long-term experience.

There is limited evidence about the real-world survival of apremilast in patients with psoriasis, especially over the long term. To evaluate the long-term survival of apremilast and its predictive factors when used to treat psoriasis. A retrospective hospital-based study, including data collected from 104 patients. Survival curves were estimated using the Kaplan-Meier estimator. Proportional hazard Cox regression models were used for multivariate analysis. The average duration of the treatment before discontinuation was 28.82 months (95% CI, 22.08-35.57 months) and the median was 12 months (95% CI, 2.68-21.31 months). The retention rates were 51% (1 year), and 33% (5 years). The survival study revealed statistically significant differences between patients with PASI<10 and those in the PASI≥10 group (log-rank test, p < 0.001). The 5-year prevalences were 64% for patients with a PASI of <10 and 5% for those with an index ≥10. In the PASI < 10-patient group, the retention rates were 77% (1 year) and 64% (5 years). Furthermore, 66% of patients who continued apremilast treatment for more than 2 years were receiving off-label doses (30 mg/day). Apremilast may be a suitable and efficient alternative for the treatment of psoriasis patients in the PASI<10 group.

Safety of biological disease-modifying antirheumatic drugs in rheumatoid arthritis.

OBJECTIVE: The aim of this study was to assess the safety of the most frequently used biologic disease-modifying antirheumatic drugs in  rheumatoid arthritis patients in clinical practice. METHOD: A retrospective longitudinal observational study was performed. Clinical information was obtained from the electronic health records of patients diagnosed and treated for rheumatoid arthritis, who had received at least one biologic disease-modifying antirheumatic drug  dispensed between 2001 and 2013 from a third-level Hospital pharmacy. Adverse reactions during biologic disease-modifying antirheumatic  drugs treatments were analysed, as well as the reasons for treatment  discontinuation. A disproportionality analysis (odds ratio with 95% confidence interval) was performed to compare adverse drug reactions related  o different system organ classes, the period between the drug start date and  the reaction start date (latency period), and previous knowledge of the adverse reactions. RESULTS: In total, 210 patients were included in the analysis (73% women, median age 47 years), with 399 prescriptions for biologic  diseasemodifying antirheumatic drugs and 1,515 adverse reactions potentially  related to them. The increased frequency of adverse reactions for  each system organ class related to each biologic disease-modifying  antirheumatic drug was as follows: general disorders and administration site disturbances with infliximab (2.3 [1.3-4.0]), infections (1.6 [1.3-2.1]) and immune system reactions with etanercept (4.2 [1.2-14.6]), hepatobiliary  disorders with adalimumab (2.1 [1.2-3.6]), ophthalmic adverse  reactions  (1.9 [1.2-3.1]) and cardiac disorders (2.9 [1.0-8.4]) with rituximab,  and blood and lymphatic system disorders with tocilizumab (2.9 [1.8-4.7])  and abatacept (3.0 [1.6-5.8)]. The mean latency period was 5 to 33 months.  Most adverse reactions were related to adalimumab (93.6%; P < 0.01),  whereas the fewest adverse reactions were related to tocilizumab (55.2%; P <  0.01). Most treatment withdrawals related to adverse reactions were identified  during the first year of biologic disease-modifying antirheumatic drugs  treatment. CONCLUSIONS: Tumour necrosis factor α inhibitors were associated with general  disorders and administration site disturbances, infections and immune system reactions, and hepatobiliary abormalities, whereas  ontumour necrosis factor α inhibitors were associated with cardiac disorders as  well as blood and lymphatic system disorders. Treatment  ithdrawals mainly occurred during the first year of treatment. Most of the  adverse reactions have been previously described.

OBJETIVO: Analizar la seguridad del tratamiento con fármacos biológicos modificadores de la enfermedad prescritos con mayor frecuencia en pacientes con artritis reumatoide en la práctica clínica habitual. Método: Estudio observacional retrospectivo, a partir de la historia clínica digitalizada de pacientes con artritis reumatoide de un hospital de tercer  nivel, sobre la seguridad de los fármacos biológicos modificadores de  la enfermedad, entre los años 2001 y 2013. Además de  analizar las reacciones adversas que motivaron la retirada del tratamiento, se  hizo un análisis de desproporcionalidad comparando los órganos y sistemas  implicados en las reacciones adversas asociadas a los diferentes  fármacos biológicos modificadores de la enfermedad calculando la odds ratio con un intervalo de confianza del 95% [odds ratio (IC95%)], del periodo de latencia entre el inicio del tratamiento y el diagnóstico de los efectos adversos, y de su conocimiento previo. RESULTADOS: Se analizaron las historias clínicas de 210 pacientes (73% mujeres; mediana de edad: 47 años), que incluían 399 líneas de  tratamiento con algún fármaco biológico modificado de la enfermedad y 1.545 reacciones adversas potencialmente relacionadas con ellos. Se identificó un incremento significativo de reacciones adversas en los siguientes  órganos y sistemas afectados: trastornos generales y del lugar de  administración [2,3 (1,3-4,0)] para infliximab; infecciones [1,6 (1,3­2,1)] y  trastornos del sistema inmunológico [4,2 (1,2-14,6)] para etanercept;  trastornos hepatobiliares [2,1 (1,2-3,6)] para adalimumab; trastornos oculares  [1,9 (1,2-3,1)]y cardiacos [2,9 (1,0-8,4)] para rituximab; trastornos  de la sangre y del  sistema linfático [2,9 (1,8-4,7)] para tocilizumab y  abatacept [3,0 (1,6-5,8)]. La latencia media osciló entre 5 y 33 meses. La  mayor y menor proporción de reacciones adversas conocidas correspondieron a  adalimumab (93,6%; p < 0,01) y tocilizumab (55,2%; p < 0,01),  respectivamente. Más de la mitad de las retiradas de fármacos biológicos  modificadores de la enfermedad asociadas a reacciones adversas se produjeron  en el primer año de tratamiento. CONCLUSIONES: Los fármacos biológicos modificadores de la enfermedad inhibidores del factor de necrosis tumoral α se asociaron a la  presentación de trastornos generales, infecciones y trastornos del sistema  inmunológico y a alteraciones hepatobiliares, mientras que los no inhibidores del factor de necrosis tumoral α se relacionaron con un incremento  en los trastornos oculares y cardiacos, trastornos de la sangre y del sistema linfático. La interrupción del tratamiento por reacciones adversas  sucedió durante el primer año. La mayoría de las reacciones adversas  registradas eran conocidas.

Medicines under additional monitoring in the European Union.

OBJECTIVE: The objective of this study was to analyse the characteristics of  medicines subject to additional monitoring. We assessed the following aspects:  the criteria applied to approve a medicine as being subject to additional  monitoring; the authorized dispensing conditions; the pharmacological groups to which they belong; and their post-authorisation safety. METHOD: We analysed the list published by the European Medicines Agency in  January 2017 (EMA/245297/2013 Rev.41). Information for the analysis was  obtained from the web sites of the European Medicines Agency and the Spanish  Agency of Medicines and Medical Devices. RESULTS: We assessed 316 medicines subject to additional monitoring. The most  common criterion used to assign a medicine as being subject to additional  monitoring was it being a new active substance (n = 197 [62.3%]). Other  common criteria were requiring a post-authorisation safety study (n = 52  [16.5%]) and being a biologic medicine but not a new active substance (n = 49  [15.5%]). Regarding dispensing conditions, nearly 66% of these medicines were authorized under restricted conditions. Until January 2017, the Spanish Agency  of Medicines and Medical Device published 14 safety reports related to medicines subject to additional monitoring. CONCLUSIONS: The group of medicines subject to additional monitoring mainly  includes new active substances. The most common pharmacological group is antineoplastic and immunomodulating agents. The postauthorisation safety  study has already produced information published by the Spanish Agency of  Medicines and Medical Devices.

Objetivo: El objetivo de nuestro estudio fue analizar las características de los  medicamentos sujetos a seguimiento adicional. Para ello, estudiamos: los  criterios aplicados para su designación, los criterios de dispensación autorizados,  los grupos farmacológicos a los que pertenecen y su seguridad postcomercialización.Método: Se analizó la lista publicada por la Agencia Europea de Medicamentos en enero de 2017 (EMA/245297/2013 Rev.41). La información para el análisis se extrajo de las páginas web de la Agencia Europea  de Medicamentos y la Agencia Española de Medicamentos y Productos  Sanitarios.Resultados: Se estudiaron 316 medicamentos sujetos a seguimiento adicional.  El criterio de designación más común fue ser un nuevo principio activo (n = 197  [62,3%]). Otros criterios de designación comunes fueron: requerir un estudio  postautorización de seguridad (n = 52 [16,5%]) y ser un medicamento  biológico, aunque no un nuevo principio activo (n = 49 [15,5%]). Con respecto a las condiciones de dispensación, casi el 66% de estos medicamentos se  autorizaron con criterios de dispensación restringidos. Hasta enero de 2017, la  Agencia Española de Medicamentos y Productos Sanitarios había publicado 14  notas informativas de seguridad referidas a los medicamentos sujetos a  seguimiento adicional.Conclusiones: Los medicamentos sujetos a seguimiento adicional incluyen mayoritariamente nuevas sustancias activas. El grupo farmacológico más frecuente es el de los fármacos antineoplásicos e  nmunomoduladores. La revisión postcomercialización de su seguridad ha  generado ya alguna información publicada por la Agencia Española de  Medicamentos y Productos Sanitarios.

What can we learn from the public's understanding of drug information and safety? A population survey.

OBJECTIVE: The aim of our study was to analyse the perceptions of the public on medicine information and safety and on consumer reporting of suspected adverse drug reactions (ADR). METHODS: A voluntary survey was conducted in a population ≥18 years of age in Asturias, a region in northern Spain. The survey was designed to be completed in a face-to-face street interview or completed independently by the public. The survey consisted of structured questions organised in four sections: (1) demographic data, (2) use of medicines, (3) reading and understanding of the patient information leaflet (PIL) and (4) awareness and perception about consumer reporting of ADR. KEY FINDINGS: A total of 402 surveys were given and analysed; 295 were completed independently and 107 were completed in street interviews. Of the population surveyed, 82.3% had taken some drug(s) in the previous 3 months, although only 62.4% had performed so by medical prescription. A quarter of respondents claimed that they never read the PIL of medicines, 12.7% that they sometimes read it, and 61.4% that they always read this information. A high percentage (82.8%) of respondents reported that they were not aware of consumer reporting of ADR, and 86.1% stated their agreement with this option. CONCLUSIONS: The public has great interest in useful information about all aspects involved in the use of medicines. This includes consumer reporting of suspected ADR, which is still unknown to many people.

Cardiovascular and gastrointestinal safety of selective cyclooxygenase-2 inhibitors: a case/non-case study.

Background Coxibs cardiovascular (CV) safety continues being a current issue after rofecoxib worldwide withdrawal in 2004. Objective To evaluate the cardiovascular and gastrointestinal (GI) risk of coxibs through case/non-case study. Setting The Spanish Pharmacovigilance System for Human Use Drugs (FEDRA) and the Uppsala Monitoring Centre (VigiBase) databases. Method We identified adverse drug reactions (ADRs) cases reported under the MedDRA system organ classes of "cardiac disorders", "vascular disorders", "nervous system disorder" and "gastrointestinal disorders". Disproportionality was considered when the following criteria were met simultaneously: proportional reporting ratio (PRR) ≥ 2, 95% confidence interval lower limit of reporting odds ratio (ROR) > 1, Chi square test (χ2) ≥ 4; and number of ADR reports (n rep.) > 3. Main outcome measure Potential disproportionality between cardiovascular and GI ADRs as reported to FEDRA and VigiBase and the use of coxibs. Results We found association between coxibs and CV-ADRs in FEDRA [PRR 2.11 (95% CI 1.97-2.27); ROR 2.53 (95% CI 2.29-2.89); χ2 367.81; n rep., 561] and VigiBase [PRR 2.67 (95% CI 2.64-2.71); ROR 3.26 (95% CI 3.20-3.31); χ2 23,950.93; n rep., 21,047]; and between coxibs and GI-ADRs in VigiBase [PRR 2.91 (95% CI 2.84-2.97); ROR 3.08 (95% CI 3.01-3.16); χ2 8762.82; n rep. 6954]. No association was found between coxibs and GI-ADRs in FEDRA. Conclusion The association found support a potential coxibs class effect in terms of cardiovascular safety. Classical NSAIDs GI risk may be higher than that for coxibs.

[The most common STOPP/START criteria in Spain. A review of the literature]. / Los criterios STOPP/START más frecuentes en España. Una revisión de la literatura.

OBJECTIVE: To analyse STOPP/START criteria found most frequently in the studies carried out in Spain, in order to identify the main areas of potentially inappropriate prescribing. METHODS: A literature review was carried out on the original studies performed in Spain that applied the original version of the STOPP/START criteria and that described the most common STOPP and/or START criteria found. In each study, a weighted analysis was performed on the criteria found, by assigning 5 points to the criterion in first position, 4 points to the criterion in second position, and so on to fifth criterion. The total points of each analysed criterion were then obtained. RESULTS: A total of 19 original studies analysing STOPP criteria were selected, 14 of them also studying all START criteria. From the total of studies, 11 were developed in out-of-hospital care, and 8 in hospital care. The STOPP criterion with the highest weighted assessment was B7 (long-term, long-acting benzodiazepines), followed by J (any duplicate drug class prescription). The START criterion with the highest weighted assessment was F4 (statin therapy in diabetes mellitus if coexisting major cardiovascular risk factors present), followed by E3 (calcium and vitamin D supplement in patients with known osteoporosis: previous fragility fracture, acquired dorsal kyphosis). CONCLUSIONS: The most common areas of potentially inappropriate prescribing are well defined, and suggest a particular intervention in some specific therapeutic points.

Updated 2014 STOPP criteria to identify potentially inappropriate prescribing in community-dwelling elderly patients
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OBJECTIVE: To analyze potentially inappropriate prescribing (PIP) using the 2014 version of STOPP criteria. MATERIALS AND METHODS: Prescriptions were analyzed by using invoicing data and electronic medical records. RESULTS: At least one STOPP criterion was observed in 9 out of every 10 patients. The most common STOPP criteria found were: "any drug prescribed without an evidence-based clinical indication" and "any drug prescribed beyond the recommended duration, where treatment duration is well defined". CONCLUSION: The high prevalence of PIP found seems to be due to the inclusion of new criteria related to indication of medication and duration of treatments.
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Spontaneous reporting of hepatotoxicity associated with antiandrogens: data from the Spanish pharmacovigilance system.

PURPOSE: To analyse the type and main features of the hepatotoxicity induced by steroidal and non-steroidal antiandrogens spontaneously reported by physicians, pharmacists and nurses. This analysis could increase the information related to these adverse reactions mainly available from the published isolated cases. METHODS: Using the Spanish Pharmacovigilance database we searched for spontaneous reports recorded since the date of approval of each antiandrogen up to the present time. We analysed the frequency of liver disorders, the preferred terms coded, the presence of other hepatotoxic drugs, and the characteristics of cases of hepatitis. RESULTS: Liver disorders were the most common adverse reactions associated with flutamide and bicalutamide, but not with cyproterone acetate. 'Hepatitis' and 'cholestatic hepatitis' were the most frequent terms coded. In 38% of the reports related to cyproterone acetate, 18% of those related to flutamide and 33% of those related to bicalutamide the patient had simultaneously received other hepatotoxic drugs. The disproportionality analysis of hepatitis showed a strong association with flutamide and a weak association with bicalutamide and cyproterone acetate. Mean doses of flutamide and bicalutamide were very close to their defined daily dose (DDD) to treat prostate cancer, although in the case of cyproterone acetate it was slightly higher. The latency period of hepatitis was between 3 and 10 months for the three antiandrogens, and the recovery period was shorter (0.5-3 months). The majority of the reported cases of hepatitis evolved favourably. CONCLUSION: Our results highlight the hepatotoxic potential of flutamide compared to cyproterone acetate. The data related to bicalutamide should be cautiously considered due to the smaller number of reports.

Hepatotoxicity induced by antiandrogens: a review of the literature.

INTRODUCTION: Hepatotoxicity is a serious adverse reaction potentially induced by all antiandrogens. We have reviewed here the published cases of hepatotoxicity induced by steroidal and nonsteroidal antiandrogens, and compared the type and characteristics of liver damage. METHODS: Using two different databases: MEDLINE and IDIS (Iowa Drug Information Service), we searched for published cases of liver injury induced by antiandrogens. Analysis was made of the type of hepatotoxicity, therapeutic indication, other pharmacological treatments and evolution. Mean values of latency and recovery periods of the adverse reactions and liver function tests were also evaluated. RESULTS: Hepatitis was the most common type of hepatotoxicity reported, and was associated with all antiandrogens. This adverse reaction does not seem to be dependent on the patients age, therapeutic indication or the dose prescribed. Hepatitis showed a longer latency period for cyproterone acetate than for flutamide. Some transaminase levels were significantly higher for flutamide than for cyproterone acetate, although the evolution was no worse in the cases reported for flutamide. We also found occasional reports of hepatocellular carcinoma and hepatic cirrhosis suspected of being induced by cyproterone acetate. CONCLUSION: Although there are differences in the clinical features of hepatotoxicity induced by steroidal and nonsteroidal antiandrogens, these do not predict which patients will develop hepatotoxicity during treatment or evolution. Serial liver function tests are required for early detection of liver damage.