The Real-World Effectiveness, Persistence, Adherence, and Safety of Janus Kinase Inhibitor Baricitinib in Rheumatoid Arthritis: A Long-Term Study.

Background/Aim: Baricitinib (BAR) is the first oral selective Janus kinase inhibitor approved in Europe for rheumatoid arthritis (RA). Real-world data are still needed to clarify its long-term benefits/risk profile. This study aimed to evaluate the effectiveness, persistence, adherence, and safety of BAR in a real-world setting. Methods: An ambispective study was conducted between October 2017 and December 2021 in RA patients starting BAR. The effectiveness was evaluated, assessing changes from the baseline of the Disease Activity Score using 28-joint counts-C reactive protein (DAS28CRP), and the achievement of low disease activity/remission. Drug persistence was evaluated using Kaplan-Meier analysis. Adherence was estimated using the medication possession ratio (MPR) and the 5-item Compliance Questionnaire for Rheumatology. Safety was assessed determining global incidence proportion and adverse event adjusted incidence rates. Results: In total, 61/64 recruited patients were finally analyzed, 83.6% were female, 78.7% were seropositive, the mean age was 58.1 (15.4) years, and the disease duration was 13.9 (8.3) years. A total of 32.8% of patients were naïve to biologics and 16.4% received BAR as monotherapy. The median exposure to BAR was 12.4 (6.6-31.2) months (range 3.1-51.4). A significant change in DAS28CRP was observed after treatment (difference -1.2, p = 0.000). 70.5% and 60.7% of patients achieved low disease activity or remission, respectively, and 50.8% (31/61) remained on BAR throughout the follow-up, with a median persistence of 31.2 (9.3-53.1) months. The average MPR was 0.96 (0.08) and all patients exhibited "good adherence" according to the questionnaire. In total, 21.3% of patients discontinued baricitinib due to toxicity. Conclusions: In our real-world practice, BAR demonstrated effectiveness, large persistence, high adherence to treatment, and an acceptable safety profile.

Defining a standard set of health outcomes for patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Standardizing health outcomes is challenging in clinical management, but it also holds the potential for creating a healthcare system that is both more effective and efficient. The aim of the present study is to define a standardized set of health outcomes for managing Relapsing-Remitting Multiple Sclerosis (RRMS). METHODS: The project was led and coordinated by a multidisciplinary scientific committee (SC), which included a literature review, a patient-focused group, three nominal group meetings, and two SC meetings. RESULTS: 36 outcome variables were included in the standard set: 24 clinical (including weight, smoking habit, comorbidities, disability, mobility, diagnosis of secondary progressive multiple sclerosis, relapsed-related variables, radiological variables, cognitive status and disease-related symptoms), nine treatment-related (pharmacological and non-pharmacological information), and 3 related to the impact of RRMS on the patient's life (quality of life, pregnancy desire, work-related difficulties). In addition, experts also agreed to collect 10 case-mix variables that may affect but cannot be controlled as part of the management of the condition: 4 sociodemographic (age, sex, race, and employment status) and 6 clinical (height, date of diagnosis and first episode, serological status, early symptoms, and number of relapses pre-diagnosis). CONCLUSION: The information provided through the present standard set of outcome variables can improve the management of RRMS and promote patient-centred quality care.

Posicionamiento de la Sociedad Española de Farmacia Hospitalaria sobre Telefarmacia. Recomendaciones para su implantación y desarrollo / Spanish Society of Hospital Pharmacy Position Statement on Telepharmacy: Recommendations for its implementation and development

En la práctica asistencial de los farmacéuticos de hospital resulta imprescindible la utilización de las tecnologías de la información y comunicación en el ámbito de la Telefarmacia. Por lo tanto, la Sociedad Española de Farmacia Hospitalaria considera oportuno definir el término y condiciones de Telefarmacia y comunicar su posicionamiento institucional a través de este documento de posicionamiento: "La Telefarmacia es la práctica farmacéutica a distancia a través del uso de las tecnologías de la información y comunicación". La Telefarmacia incluye como principales actividades: validación terapéutica, documentación clínica, consulta de atención farmacéutica, monitorización terapéutica, seguimiento de la adherencia, formación/información sobre medicamentos, coordinación con profesionales sanitarios y evaluación de resultados en salud. Los procedimientos asistenciales en el ámbito de la Telefarmacia deben regirse por un Procedimiento Normalizado de Trabajo, con documentación en la historia clínica y sin discriminación de acceso a pacientes candidatos. Se consideran cuatro procedimientos principales de Telefarmacia: seguimiento farmacoterapéutico; información y/o formación a pacientes y cuidadores; coordinación con el equipo multidisciplinar a nivel intra y extrahospitalario; dispensación y entrega informada de medicamentos a distancia. La implantación de la Telefarmacia requiere adecuación de medios humanos (formación, capacitación) y tecnológicos (validación, interoperatividad, confidencialidad). Asimismo, debe dar cumplimiento a la legalidad y normativa vigente, tanto a nivel autonómico como estatal. Los procedimientos de Telefarmacia deben también ajustarse a las consideraciones éticas y los códigos deontológicos pertinentes. Debe fomentarse la evaluación de la Telefarmacia a través del uso de indicadores y de la investigación de su repercusión sobre los resultados en salud. Por tanto, la Sociedad Española de Farmacia Hospitalaria considera que la Telefarmacia es una herramienta complementaria y necesaria para la provisión de una Atención Farmacéutica Especializada con el objetivo final de mejorar los resultados en salud y maximizar la seguridad y satisfacción de los pacientes

The use of information and communication technologies have nowadays become part and parcel of hospital pharmacy practice. Against this background, it is hardly surprising that Telepharmacy has sparked the interest of a large number of stakeholders. In this respect, the Spanish Society of Hospital Pharmacy has developed a definition of the concept and outlined the conditions under which Telepharmacy should operate. It has also shared its institutional stance on the subject through a position statement that states that Telepharmacy is the provision of pharmaceutical care at a distance through information and communication technologies. Telepharmacy practice includes activities such as therapeutic validation, drafting of clinical documents, provision of pharmaceutical care, therapeutic follow-up, adherence monitoring, drug education and information, coordination between healthcare providers and evaluation of health outcomes. The clinical tasks performed as part of Telepharmacy practice must adhere to a standardized procedure and revolve around the patient's clinical record. Access to Telepharmacy must be provided without discrimination. The service comprises four main activities: pharmacotherapeutic follow-up; patient and caregiver-directed education and information-dissemination; coordination with healthcare providers from the same or different hospitals; and remote informed home drug delivery. Implementation of Telepharmacy requires an adjustment of human (training and capacity-building) and technological resources (validation, interoperability, confidentiality). It must also comply with the laws and regulations in force both at a regional and a national level. Telepharmacy procedures must also be adapted to the relevant ethical standards and codes of good practice. Appropriate indicators must be used to evaluate the performance of Telepharmacy and its impact on health outcomes. According to Spanish Society of Hospital Pharmacy Telepharmacy is a necessary complemetary tool to provide specialized pharmaceutical care and thereby improve health outcomes and maximize patient safety and satisfaction

Spanish Society of Hospital Pharmacy Position Statement on Telepharmacy: Recommendations for its implementation and development.

The use of information and communication technologies have nowadays become  part and parcel of hospital pharmacy practice. Against this background, it is  hardly surprising that Telepharmacy has sparked the interest of a large number  of stakeholders. In this respect, the Spanish Society of Hospital Pharmacy has  developed a definition of the concept and outlined the conditions under which  Telepharmacy should operate. It has also shared its institutional stance on the  subject through a position statement that states that Telepharmacy is the  provision of pharmaceutical care at a distance through information and  communication technologies. Telepharmacy practice includes activities such as  therapeutic validation, drafting of clinical documents, provision of  pharmaceutical care, therapeutic follow-up, adherence monitoring, drug  education and information, coordination between healthcare providers and  evaluation of health outcomes. The clinical tasks performed as part of  Telepharmacy practice must adhere to a standardized procedure and revolve  around the patient's clinical record. Access to Telepharmacy must be provided without discrimination. The service comprises four main activities:  pharmacotherapeutic follow-up; patient and caregiver-directed education and information-dissemination; coordination with healthcare providers from the  same or different hospitals; and remote informed home drug delivery. Implementation of Telepharmacy requires an adjustment of human (training and capacity-building) and technological resources (validation, interoperability, confidentiality). It must also comply with the laws and regulations in force both  at a regional and a national level. Telepharmacy procedures must also be  adapted to the relevant ethical standards and codes of good practice.  Appropriate indicators must be used to evaluate the performance of  Telepharmacy and its impact on health outcomes. According to Spanish Society  of Hospital Pharmacy Telepharmacy is a necessary complementary tool to  provide specialized pharmaceutical care and thereby improve health outcomes  and maximize patient safety and satisfaction.

En la práctica asistencial de los farmacéuticos de hospital resulta imprescindible la utilización de las tecnologías de la información y comunicación en el ámbito de la Telefarmacia. Por lo tanto, la Sociedad Española e Farmacia Hospitalaria considera oportuno definir el término y condiciones de  Telefarmacia y comunicar su posicionamiento institucional a través de este  documento de posicionamiento: "La Telefarmacia es la práctica farmacéutica a  distancia a través del uso de las tecnologías de la información y comunicación".  La Telefarmacia incluye como principales actividades: validación terapéutica,  documentación clínica, consulta de atención farmacéutica, monitorización  terapéutica, seguimiento de la adherencia, formación/información sobre  medicamentos, coordinación con profesionales sanitarios y evaluación de  resultados en salud. Los procedimientos asistenciales en el ámbito de la  Telefarmacia deben regirse por un Procedimiento Normalizado de Trabajo, con  documentación en la historia clínica y sin discriminación de acceso a pacientes  candidatos. Se consideran cuatro procedimientos principales de Telefarmacia:  seguimiento farmacoterapéutico; información y/o formación a pacientes y  cuidadores; coordinación con el equipo multidisciplinar a nivel intra y  extrahospitalario; dispensación y entrega informada de medicamentos a  distancia. La implantación de la Telefarmacia requiere adecuación de medios  humanos (formación, capacitación) y tecnológicos (validación, interoperatividad, confidencialidad). Asimismo, debe dar cumplimiento a la legalidad y normativa  vigente, tanto a nivel autonómico como estatal. Los procedimientos de  Telefarmacia deben también ajustarse a las consideraciones éticas y los códigos  deontológicos pertinentes. Debe fomentarse la evaluación de la Telefarmacia a  través del uso de indicadores y de la investigación de su repercusión sobre los  resultados en salud. Por tanto, la Sociedad Española de Farmacia Hospitalaria  considera que la Telefarmacia es una herramienta complementaria y necesaria  para la provisión de una Atención Farmacéutica Especializada con el objetivo  final de mejorar los resultados en salud y maximizar la seguridad y satisfacción  de los pacientes.

Factores asociados a la persistencia a largo plazo de rituximab en artritis reumatoide en la práctica clínica: Estudio RITAR / Factors associated with long-term persistence of rituximab in rheumatoid arthritis In clinical practice: RITAR Study

ANTECEDENTES Y OBJETIVO: El tratamiento de la artritis reumatoide con rituximab (RTX) requiere ciclos repetidos y no existe una pauta bien establecida en dosis y frecuencia de retratamiento. El objetivo fue analizar la persistencia del tratamiento con RTX y los factores que influyen en condiciones de práctica clínica habitual. MATERIALES Y MÉTODOS: RITuximab en Artritis Reumatoide (Estudio RITAR) es un estudio observacional, retrospectivo que analiza la persistencia de RTX en una cohorte desde 2003 hasta 2015. La persistencia se calculó por análisis de Kaplan-Meier, las curvas se compararon con el test del Log-Rank. Para cuantificar el riesgo de suspensión se utilizó la regresión de Cox, se realizaron análisis multivariables para determinar los factores asociados a la persistencia del tratamiento. RESULTADOS: Se incluyeon 454 ciclos de RTX pertenecientes a 114 pacientes. La mediana de supervivencia fue 10 años y la tasa de incidencia de suspensión 7,7 por cada 100 pacientes-año. Los factores asociados a la persistencia fueron la seropositividad, el uso de RTX combinado con FAMEsc. No estuvieron asociados sexo, edad, n.° de comorbilidades, tiempo de evolución, n.° de complicaciones, DAS28 basal, HAQ basal, número de líneas de tratamiento, pauta de retratamiento fijo o a demanda, año de inicio de RTX. Los modelos multivariables confirmaron la relación entre seropositividad, uso en monoterapia y persistencia de RTX. CONCLUSIONES: La persistencia de RTX en la práctica clínica es elevada en pacientes seropositivos y en aquellos que están tratados con RTX asociado a un FAMEsc. La dosis por ciclo y la frecuencia de retratamiento no tienen un papel determinante en la persistencia

BACKGROUND AND OBJECTIVE: Treatment of rheumatoid arthritis with rituximab (RTX) requires repeated cycles, but there is no well-established retreatment regimen in dose and frequency. The objective was to analyse the persistence of RTX treatment and factors that influence in terms of routine clinical practice. METHODS: Rituximab in Rheumatoid Arthritis (RITAR Study) is an observational, retrospective study that analyses the persistence of RTX in a cohort from 2003 to 2015. Persistence was calculated by the Kaplan-Meier analysis; curves were compared with the Log-Rank test. Cox regression was used to quantify the risk of discontinuation and multivariate analyses were conducted to determine the factors associated with the persistence of the treatment. RESULTS: 454 cycles of RTX in 114 patients were included. Median survival was 10.0 years and incidence rate of discontinuation was 7.7 per 100 patients/year. Factors associated with persistence were autoantibody positivity and use of RTX in combination with csDMARDs. Sex, age, number of comorbidities, rheumatoid arthritis evolution, number of complications, basal DAS28, basal HAQ, number of lines of treatment, fixed or on demand retreatment and year of RTX starting were not associated. Multivariable models confirmed the relationship between autoantibody positivity, monotherapy and persistence of RTX. CONCLUSIONS: The persistence of RTX in clinical practice is higher in seropositive patients and in those who are treated with RTX associated with a csDMARD. Dose per cycle and retreatment frequency do not have a decisive role in rituximab persistence

Factors associated with long-term persistence of rituximab in rheumatoid arthritis In clinical practice: RITAR Study. / Factores asociados a la persistencia a largo plazo de rituximab en artritis reumatoide en la práctica clínica: Estudio RITAR.

BACKGROUND AND OBJECTIVE: Treatment of rheumatoid arthritis with rituximab (RTX) requires repeated cycles, but there is no well-established retreatment regimen in dose and frequency. The objective was to analyse the persistence of RTX treatment and factors that influence in terms of routine clinical practice. METHODS: Rituximab in Rheumatoid Arthritis (RITAR Study) is an observational, retrospective study that analyses the persistence of RTX in a cohort from 2003 to 2015. Persistence was calculated by the Kaplan-Meier analysis; curves were compared with the Log-Rank test. Cox regression was used to quantify the risk of discontinuation and multivariate analyses were conducted to determine the factors associated with the persistence of the treatment. RESULTS: 454 cycles of RTX in 114 patients were included. Median survival was 10.0 years and incidence rate of discontinuation was 7.7 per 100 patients/year. Factors associated with persistence were autoantibody positivity and use of RTX in combination with csDMARDs. Sex, age, number of comorbidities, rheumatoid arthritis evolution, number of complications, basal DAS28, basal HAQ, number of lines of treatment, fixed or on demand retreatment and year of RTX starting were not associated. Multivariable models confirmed the relationship between autoantibody positivity, monotherapy and persistence of RTX. CONCLUSIONS: The persistence of RTX in clinical practice is higher in seropositive patients and in those who are treated with RTX associated with a csDMARD. Dose per cycle and retreatment frequency do not have a decisive role in rituximab persistence.

Inhibidores de la vía de señalización JAK-STAT en el tratamiento de las enfermedades inmunomediadas / JAK-STAT inhibitors for the treatment of immunomediated diseases

La ruta de señalización de las proteínas de la familia Janus cinasa (JAK) está implicada en la patogenia de muchas enfermedades inflamatorias y autoinmunitarias, como la artritis reumatoide (AR), la psoriasis y la enfermedad inflamatoria intestinal. Una gran cantidad de citocinas implicadas en el desarrollo de estas enfermedades utilizan esta vía de señalización para transducir señales intracelulares. En los últimos años, la aparición de los inhibidores de las proteínas JAK (jakinibs) ha demostrado que los fármacos relacionados con esta ruta patogénica pueden tener gran aplicabilidad clínica. Tofacitinib y baricitinib, primeros jakinibs aprobados para el tratamiento de la AR, están en estudio para el tratamiento de otras enfermedades autoinmunitarias. Asimismo, otros jakinibs se encuentran en diferentes fases de desarrollo. En este trabajo se revisan los principales aspectos en cuanto a eficacia, interacciones farmacológicas y seguridad tanto de los jakinibs clásicos como de los de nueva generación

The Janus kinase (JAK) pathway is implicated in the pathogenesis of many inflammatory and autoimmune diseases including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. There are a lot of proinflammatory cytokines involved in such diseases using this pathway to transduce intracellular signals. In the last years, JAK inhibitors (jakinibs) have appeared with a great success, showing that these kinds of drugs have a great applicability in clinical practice. Tofacitinib and baricitinib, the first jakinibs approved for the treatment of RA, are being investigated also for treating other autoimmune systemic diseases. Likewise, other jakinibs are in several phases of development. This review analyses the safety and clinical efficacy of the jakinibs, starting with the classics and continuing with next-generation jakinibs

JAK-STAT inhibitors for the treatment of immunomediated diseases. / Inhibidores de la vía de señalización JAK-STAT en el tratamiento de las enfermedades inmunomediadas.

The Janus kinase (JAK) pathway is implicated in the pathogenesis of many inflammatory and autoimmune diseases including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. There are a lot of proinflammatory cytokines involved in such diseases using this pathway to transduce intracellular signals. In the last years, JAK inhibitors (jakinibs) have appeared with a great success, showing that these kinds of drugs have a great applicability in clinical practice. Tofacitinib and baricitinib, the first jakinibs approved for the treatment of RA, are being investigated also for treating other autoimmune systemic diseases. Likewise, other jakinibs are in several phases of development. This review analyses the safety and clinical efficacy of the jakinibs, starting with the classics and continuing with next-generation jakinibs.

Interacciones farmacológicas de los anticuerpos monoclonales / Pharmacological interactions of monoclonal antibodies

Las interacciones farmacológicas de los agentes biológicos no son bien conocidas. Debido a que los fármacos biológicos no son metabolizados por las enzimas del citocromo P450 (CYP450) ni interaccionan con los transportadores transmembrana, existe la percepción de que estos no presentan interacciones medicamentosas con los fármacos de síntesis química. Sin embargo, el aclaramiento de los agentes biológicos puede variar en función de la respuesta inmune o si se modifica la expresión de sus células diana, lo cual puede ocurrir por la acción de muchos agentes químicos. Además, algunos biológicos son capaces de modular la expresión de las enzimas del sistema CYP450. En esta revisión, se proporciona una descripción de las propiedades farmacocinéticas y posibles interacciones de los fármacos biológicos, centrándonos en los anticuerpos monoclonales, y como estos pueden interaccionar con las moléculas de síntesis química. Creemos que su conocimiento es importante para los clínicos y afecta a varias especialidades médicas

The pharmacological interactions of biological agents are not well known. Because biologic agents are not metabolised by cytochrome P450 (CYP) enzymes and do not interact with cell membrane transporters, it is generally perceived that they are free from interactions with small molecule drugs. However, the clearance of biological agents varies depending on the modulation of the immune response or by either increasing or reducing the expression of target cells of the biological agents, which can occur through the action of multiple synthetic chemical agents. Furthermore, some biological agents may modify the metabolism of chemical drugs through their effects on the expression of P450 system enzymes.. In this review, we will provide an outline of the pharmacokinetics properties and pharmacologic interactions of biological drugs, focusing on monoclonal antibodies, and how these can interact with chemical synthesis molecules. We believe knowledge of them is important for clinicians and affects multiple clinical specialties

Pharmacological interactions of monoclonal antibodies. / Interacciones farmacológicas de los anticuerpos monoclonales.

The pharmacological interactions of biological agents are not well known. Because biologic agents are not metabolised by cytochrome P450 (CYP) enzymes and do not interact with cell membrane transporters, it is generally perceived that they are free from interactions with small molecule drugs. However, the clearance of biological agents varies depending on the modulation of the immune response or by either increasing or reducing the expression of target cells of the biological agents, which can occur through the action of multiple synthetic chemical agents. Furthermore, some biological agents may modify the metabolism of chemical drugs through their effects on the expression of P450 system enzymes.. In this review, we will provide an outline of the pharmacokinetics properties and pharmacologic interactions of biological drugs, focusing on monoclonal antibodies, and how these can interact with chemical synthesis molecules. We believe knowledge of them is important for clinicians and affects multiple clinical specialties.

Fármacos biosimilares: un nuevo escenario en las terapias biológicas / Biosimilars: a new scenario in biologic therapies

No cabe duda de que los productos biológicos aportan un valor añadido a los sistemas de salud, aunque también plantean grandes interrogantes debido a su especial naturaleza, lo que obliga a ser muy rigurosos y exigentes en su control de calidad y seguimiento. Este hecho se ha visto reforzado por la entrada en escena de los fármacos biosimilares, cuyo menor coste está permitiéndoles alcanzar un mayor protagonismo en el mercado mundial. El propósito de este artículo es revisar en profundidad los principales interrogantes que se plantean en su producción, distribución y control, así como los aspectos más importantes relacionados con su seguridad en la práctica clínica. En este trabajo revisamos lo que representa la farmacovigilancia de estos productos, prestando especial atención a su trazabilidad, como herramienta fundamental para la detección precoz de acontecimientos adversos (AU)

There is no doubt that biologic therapies provide added value for health systems. However, due to their special nature, they also raise some questions that make highly rigorous and demanding quality control and monitoring of their use indispensable. This circumstance is reinforced with the appearance on the scene of biosimilars, which, given their lower cost, are having an increasing impact on the international market. The purpose of this article is to review the major issues posed by their manufacture, distribution and control systems, as well as the most important aspects related to their safety in clinical practice. In this report, we assess the pharmacovigilance of these products, with special attention to traceability, as a key tool to enable earlier detection of adverse events (AU)

How to select a nanosimilar.

Nanomedicines in the class of nonbiological complex drugs (NBCDs) are becoming increasingly available. Up to 23 nanomedicines have been approved, and approximately 50 are in clinical development. Meanwhile, the first nanosimilars have entered the market through the generic approval pathway, but clinical differences have been observed. Many healthcare professionals may be unaware of this issue and must be informed of these clinically relevant variances. This article provides a tool for rational decision making for the inclusion of nanomedicines into the hospital formulary, including defined criteria for evaluation of substitutability or interchangeability. The tool was generated by conducting a roundtable with an international panel of experts and follows the same thought process that was developed and published earlier for the selection of biologicals/biosimilars. In addition to the existing criteria for biosimilars, a set of seven criteria was identified that specifically apply to nanosimilars. These include (1) particle size and size distribution, (2) particle surface characteristics, (3) fraction of uncaptured bioactive moiety, (4) stability on storage, (5) bioactive moiety uptake and (6) distribution, and (7) stability for ready-to-use preparation. Pharmacists should utilize their pharmaceutical expertise to use the appropriate criteria to evaluate the comparability of the drug to decide on interchangeability or substitutability.

Biosimilars: A new scenario in biologic therapies. / Fármacos biosimilares: un nuevo escenario en las terapias biológicas.

There is no doubt that biologic therapies provide added value for health systems. However, due to their special nature, they also raise some questions that make highly rigorous and demanding quality control and monitoring of their use indispensable. This circumstance is reinforced with the appearance on the scene of biosimilars, which, given their lower cost, are having an increasing impact on the international market. The purpose of this article is to review the major issues posed by their manufacture, distribution and control systems, as well as the most important aspects related to their safety in clinical practice. In this report, we assess the pharmacovigilance of these products, with special attention to traceability, as a key tool to enable earlier detection of adverse events.

Efficiency of adalimumab, etanercept and infliximab in ankylosing spondylitis in clinical practice.

BACKGROUND: Information on the use of ankylosing spondylitis (AS) therapies in clinical practice is a key factor in decision making, as more efficient treatments may involve substantial savings while maintaining the clinical benefits for the patient. OBJECTIVE: To assess the mean annual doses and associated costs of the three main anti-tumour necrosis factor agents used in Spanish daily clinical practice in ankylosing spondylitis patients and to correlate these costs with disease activity. SETTING: This retrospective, observational study included adult ankylosing spondylitis patients over a 4-year period that had been treated for at least 6 months with adalimumab, etanercept or infliximab at two University Hospitals in Spain. METHODS: Disease activity was estimated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores at the start of anti-tumour necrosis factor (anti-TNF) therapy and in the last visit or whenever the drug was switched. Mean costs were estimated for a 52-week horizon from the delivered doses registered by pharmacy records. Outcomes were the doses and costs of anti TNFs administered to each patient, and the BASDAI score. RESULTS: A total of 119 patients (137 cases) were included (28 cases treated with adalimumab, 48 cases with etanercept and 61 with infliximab). Mean doses of adalimumab and etanercept were 92.8 and 88.8% of the initially prescribed doses, respectively, while the mean dose of infliximab administered was 102%. There were no statistical differences among treatments in terms of clinical effectiveness. Associated mean patient-year costs were significantly higher in the infliximab group (€14,235), compared to the other treatments [adalimumab €11,934; etanercept €10,516; (P < 0.05)]. CONCLUSION: In certain ankylosing spondylitis patients, doses and associated costs of biological therapies can be reduced while controlling disease activity. Mean doses used in our clinical practice vary from the recommended doses and are significantly lower for adalimumab and etanercept than for infliximab. These differences impact directly on associated patient-year costs, and, thus, on treatment efficiency.

Spanish Rheumatology Society and Hospital Pharmacy Society Consensus on recommendations for biologics optimization in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.

OBJECTIVE: The aim of this study was to establish guidelines for the optimization of biologic therapies for health professionals involved in the management of patients with RA, AS and PsA. METHODS: Recommendations were established via consensus by a panel of experts in rheumatology and hospital pharmacy, based on analysis of available scientific evidence obtained from four systematic reviews and on the clinical experience of panellists. The Delphi method was used to evaluate these recommendations, both between panellists and among a wider group of rheumatologists. RESULTS: Previous concepts concerning better management of RA, AS and PsA were reviewed and, more specifically, guidelines for the optimization of biologic therapies used to treat these diseases were formulated. Recommendations were made with the aim of establishing a plan for when and how to taper biologic treatment in patients with these diseases. CONCLUSION: The recommendations established herein aim not only to provide advice on how to improve the risk:benefit ratio and efficiency of such treatments, but also to reduce variability in daily clinical practice in the use of biologic therapies for rheumatic diseases.

Efficiency of adalimumab, etanercept and infliximab in rheumatoid arthritis patients: dosing patterns and effectiveness in daily clinical practice.

OBJECTIVES: This retrospective, multicentre, observational study aimed to assess the mean annual doses and associated costs of three anti-tumour necrosis factor agents in daily clinical practice in rheumatoid arthritis patients, correlating these costs with disease activity. METHODS: Adult rheumatoid arthritis patients were treated and followed at the Rheumatology departments of two Spanish hospitals for at least 6 months, with adalimumab, etanercept or infliximab over a 4-year period. ANOVA and multivariate statistical analyses of dosing patterns, disease activity and annualised costs were carried out. RESULTS: A total of 198 patients, comprising 215 cases, met the inclusion criteria (73 on adalimumab, 81 etanercept and 61 infliximab). Compared to recommended doses, mean doses of adalimumab and etanercept decreased by 7% and 19%, respectively, while the mean dose of infliximab increased by 36%. There were no statistical differences between treatments in terms of clinical effectiveness. The hazard of dose escalation was significantly higher for either adalimumab (4.4-fold) or infliximab (11.8-fold) compared to etanercept (p<0.05). Clinical control was achieved and maintained in more than half of the patients treated with reduced doses of etanercept. Associated mean patient-year costs were significantly higher in adalimumab patients (€11.962.58) (etanercept €9.594.73; infliximab €10.094.53; [p<0.05]). CONCLUSIONS: In rheumatoid arthritis patients, it is possible to reduce doses and associated costs of biological therapies while controlling disease activity. Mean doses used in our clinical practice were significantly lower with etanercept than with the anti-TNF monoclonal antibodies, adalimumab and infliximab. Dose differences impact directly on associated patient-year costs, and thus on treatment efficiency.

Influence on effectiveness of early treatment with anti-TNF therapy in rheumatoid arthritis.

PURPOSE: To evaluate the association between starting early treatment with anti-TNF and effectiveness as well as the possibility of applying therapeutic spacing in daily practice in patients with rheumatoid arthritis (RA). METHODS: Observational, retrospective study conducted in two universitary hospitals in Spain. RA patients who received the first anti-TNF (adalimumab: ADA, etanercept: ETN or infliximab: IFX) during the study period (October 2006-2010) were included. Demographic data, time since diagnosis, disease activity (DAS28-ESR) and anti-TNF dosage were analyzed. Therapeutic objective was defined as DAS28 DAS28 < 2.6. Also the response related to criteria of the European League Against Rheumatism (EULAR) was evaluated. Therapeutic spacing was defined as the use of a lower dose or a higher interval according to label doses. The main endpoint was to assess the association between the effectiveness and the moment when the anti-TNF therapy begins. The secondary target was to evaluate the association between RA activity at the beginning of treatment with anti-TNF and dose used. Results. 82 patients were included. The prescription profile was: ADA (48.8%), ETN (31.7%) and IFX (19.5%). 71.4% of patients treated with anti-TNF during the first year since diagnosis, 57.1% of those who started after 1-5 years and 30.6% of patients who started after 5 years were in remission when the study ended. De-escalation strategy was performed in 25.6% of patients: ETN (38.5%), ADA (20.0%) and IFX (18.8%). The patients treated with a higher dose according to label doses were: IFX (81%), ADA, (12.5%) and ETN (7.7%). CONCLUSIONS: Results suggest that early treatment with anti-TNF can achieve a higher percentage of remissions. Therapeutic spacing is established as a strategy that improves the efficiency in those patients in remission, being the ETN the anti-TNF most susceptible for spacing, although a relation between the early beginning with anti-TNF and the used dose was not found.