Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

Prevalencia, factores de riesgo y respuesta al tratamiento de las manifestaciones extraintestinales en pacientes con enfermedad inflamatoria intestinal / Prevalence, risk factors and response to treatment of extra-intestinal manifestations in patients with inflammatory bowel disease

Introducción: los pacientes con enfermedad inflamatoria intestinal pueden presentar manifestaciones extraintestinales que en ocasiones asocian gran morbilidad. Objetivos: evaluar la prevalencia, las características, los tratamientos y la evolución de las manifestaciones extraintestinales en pacientes con enfermedad inflamatoria intestinal en nuestro centro e identificar los posibles factores de riesgo asociados. Métodos: estudio retrospectivo, observacional, tipo casos y controles. Los pacientes con enfermedad inflamatoria intestinal con manifestaciones extraintestinales fueron considerados casos y los que no las presentaban, controles. Resultados: fueron incluidos 619 pacientes con enfermedad inflamatoria intestinal (327 enfermedad de Crohn, 265 colitis ulcerosa, 27 colitis no clasificada). El 16,5% mostró al menos una manifestación extraintestinal (IC 95% 13,5-19,5; n = 102), siendo las más frecuentes las musculoesqueléticas (n = 50, 40%) y las cutáneas (n = 50, 40%). Respecto al tratamiento, en las artropatías predominó el uso de antiinflamatorios no esteroideos (31%) y corticoides (19%, orales o intraarticulares) y para las alteraciones cutáneas se recurrió mayoritariamente a los corticoides (83%). Globalmente, la eficacia del tratamiento fue del 90%. En el 13% se produjo recidiva de la manifestación extraintestinal. El análisis multivariante identificó el sexo femenino (p = 0,012; OR = 1,61; IC 95% 1,11-2,34) y la gravedad de la enfermedad inflamatoria intestinal (p = 0,009, OR = 1,65, 1,13-2,4, si precisaron terapia inmunosupresora; p = 0,029, OR = 2,28, 1,09-4,78, si requirieron terapia combinada con inmunosupresor y adalimumab) como factores de riesgo asociados al desarrollo de manifestaciones extraintestinales. Conclusiones: las manifestaciones extraintestinales más frecuentes en nuestro medio son las musculoesqueléticas y las cutáneas. El sexo femenino y la gravedad de la enfermedad inflamatoria intestinal asocian un mayor riesgo de desarrollar manifestaciones extraintestinales. El tratamiento individualizado de las mismas es eficaz y el porcentaje de recidiva es bajo (AU)

Introduction: Patients with inflammatory bowel disease can experience extra-intestinal manifestations that may cause significant morbidity. Aims: To describe the prevalence, characteristics, treatment and evolution of extra-intestinal manifestations in inflammatory bowel disease patients treated in our hospital and to identify associated risk factors. Methods: This was a retrospective, observational, case-control study. All inflammatory bowel disease patients with extra-intestinal manifestations were considered as cases and inflammatory bowel disease patients without extra-intestinal manifestations were considered as controls. Results: Six hundred and nineteen patients with inflammatory bowel disease (327 Crohn’s disease, 265 ulcerative colitis, 27 indeterminate colitis) were included in the study; 16.5% experienced at least one extra-intestinal manifestation (CI 95% 13.5-19.5; n = 102). The most frequent extra-intestinal manifestations observed were musculoskeletal (n = 50; 40%) and cutaneous manifestations (n = 50; 40%). With regard to treatment, arthropathies were treated with non-steroidal anti-inflammatory drugs (31%) and corticosteroids (19%, oral or intra-articular), and the majority of the cutaneous manifestations were managed with corticosteroids. Overall, the efficacy of extra-intestinal manifestation treatment was 90% and only 13% of patients had a recurrence of extra-intestinal manifestations. The multivariate analysis showed that female gender (p = 0.012; OR = 1.61; 95% CI 1.11-2.34) and the severity of inflammatory bowel disease (p = 0.009; OR = 1.65; 95% CI 1.13-2.4 if immunosuppressant therapy alone, or p = 0.029; OR = 2.28; 95% CI 1.09-4.78 if in combination with adalimumab) were associated with an increased risk of developing extra-intestinal manifestations. Conclusions: The most frequent extra-intestinal manifestations in our environment were musculoskeletal and cutaneous manifestations. Female gender and a more severe disease were associated with a higher risk of developing extra-intestinal manifestations. Individualized treatment of extra-intestinal manifestations is effective and the risk is low in our series (AU)

Prevalence, risk factors and response to treatment of extra-intestinal manifestations in patients with inflammatory bowel disease.

INTRODUCTION: Patients with inflammatory bowel disease can experience extra-intestinal manifestations that may cause significant morbidity. AIMS: To describe the prevalence, characteristics, treatment and evolution of extra-intestinal manifestations in inflammatory bowel disease patients treated in our hospital and to identify associated risk factors. METHODS: This was a retrospective, observational, case-control study. All inflammatory bowel disease patients with extra-intestinal manifestations were considered as cases and inflammatory bowel disease patients without extra-intestinal manifestations were considered as controls. RESULTS: Six hundred and nineteen patients with inflammatory bowel disease (327 Crohn's disease, 265 ulcerative colitis, 27 indeterminate colitis) were included in the study; 16.5% experienced at least one extra-intestinal manifestation (CI 95% 13.5-19.5; n = 102). The most frequent extra-intestinal manifestations observed were musculoskeletal (n = 50; 40%) and cutaneous manifestations (n = 50; 40%). With regard to treatment, arthropathies were treated with non-steroidal anti-inflammatory drugs (31%) and corticosteroids (19%, oral or intra-articular), and the majority of the cutaneous manifestations were managed with corticosteroids. Overall, the efficacy of extra-intestinal manifestation treatment was 90% and only 13% of patients had a recurrence of extra-intestinal manifestations. The multivariate analysis showed that female gender (p = 0.012; OR = 1.61; 95% CI 1.11-2.34) and the severity of inflammatory bowel disease (p = 0.009; OR = 1.65; 95% CI 1.13-2.4 if immunosuppressant therapy alone, or p = 0.029; OR = 2.28; 95% CI 1.09-4.78 if in combination with adalimumab) were associated with an increased risk of developing extra-intestinal manifestations. CONCLUSIONS: The most frequent extra-intestinal manifestations in our environment were musculoskeletal and cutaneous manifestations. Female gender and a more severe disease were associated with a higher risk of developing extra-intestinal manifestations. Individualized treatment of extra-intestinal manifestations is effective and the risk is low in our series.

Adhesión al tratamiento en la enfermedad inflamatoria intestinal: estrategias para mejorarla / Treatment adherence in inflammatory bowel disease. Strategies for improvement

La enfermedad inflamatoria intestinal constituye una entidad clínica en la que hay un riesgo elevado de baja adhesión al tratamiento, debido a que se trata de una enfermedad crónica que afecta con frecuencia a pacientes jóvenes, y que precisa terapias prolongadas en el tiempo y con períodos de inactividad clínica. Diversos factores infl uyen en la adhesión: las características del paciente y de su enfermedad, la complejidad de su tratamiento y la relación médico-paciente. Debemos intentar detectar la falta de adhesión y tratarla, dada su importancia en los resultados del tratamiento. Para ello podemos realizar un control sistemático en la consulta o centrar la vigilancia en los pacientes no respondedores o en aquellos con factores de riesgo para falta de adhesión. Una buena relación médico-paciente y acciones específi cas, como la optimización de la información que se proporciona al paciente acerca de su enfermedad y la elasticidad en la posología respetando la opinión del paciente, pueden ayudar a lograr una buena adhesión al tratamiento (AU)

Since inflammatory bowel disease (IBD) is a chronic condition that frequently affects young patients, requires prolonged therapy and is characterized by periods of clinical remission, there is a risk of low treatment adherence. Adherence is infl uenced by several factors: disease and patient characteristics, treatment complexity and the physicianpatient relationship. Given the importance of adherence in treatment results, lack of adherence should be detected and treated. To do this, systematic surveillance can be performed in consultations or can be centered on non-responders or patients with risk factors for lack of adherence. Elements that help to achieve good treatment adherence are a good physician-patient relationship and specifi c actions, such as optimizing the information provided to patients on their disease and dosage adjustments taking the patient’s opinion into consideration (AU)