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Background: Ustekinumab is used to treat inflammatory bowel disease mainly in patients failing anti-tumour necrosis factor (TNF)-agents. Objectives: To provide real-world data in unselected patients with Crohn's disease (CD), treated with ustekinumab. Design: Longitudinal retrospective study at four hospitals in Stockholm, Sweden. Methods: Disease activity (Harvey-Bradshaw index and physician global assessment), laboratory parameters, endoscopic findings and drug persistence were assessed. Follow-up data were obtained in patients that stopped ustekinumab. Results: In total, 322 patients (median age 38 years, 48% women) were included. All had luminal disease and 22% also fistulizing disease. A total of 271 (84%) had failed ⩾1 and 148 (46%) ⩾2 anti-TNF drugs; 34% failed vedolizumab. At inclusion, 93% had active disease; 28% were on oral corticosteroids and 18% on thiopurines. The median follow-up on treatment was 13.5 months; overall 67% were followed at least 24 months. By intention to treat analysis, response rate at 3 and 12 months was 43% and 42%, respectively. Among patients with ongoing ustekinumab, 19% were in steroid-free remission at 3 months and 64% at 12 months. The median faecal calprotectin level decreased from 460 µg/g at baseline to 156 µg/g at 3 months and was 182 µg/g at 12 months. C-reactive protein remained stable at 4 mg/L whereas serum albumin increased slightly. About 31% of patients were withdrawn during the first 12 months, mainly due to persisting disease activity 21%, adverse events 5%, bowel surgery 0.6% or malignancy 0.3%. The overall persistence on ustekinumab was 88%, 51%, 34% and 20% at 3, 12, 24 and 36 months, respectively. Within 12 months following withdrawal of ustekinumab in 121 patients, 64% had active disease most of the time, 68% needed another biologic and 24% underwent surgery. Conclusion: Among difficult-to-treat patients with CD, ustekinumab was effective in the majority, with high drug persistence at 12 and 24 months in combination with a favourable safety profile.
Study of a new biologic treatment in patients with Crohn's disease that have failed previous medications Why was the study done? New medical treatments become available in routine healthcare after rigorous testing on selected groups of patients in what is called clinical trials. The benefits and possible adverse events then need to be assessed in larger groups of unselected patients to gain a more generalizable knowledge of merits and shortfalls. Therefore studies in real-world settings are vital to complement the experience gained from clinical trials and they can provide robust data and reveal previously undetected safety issues. What did the researchers do? The research team studied the effect of a new injectable biological treatment, ustekinumab, in a large group of Swedish patients with an inflammatory bowel disease, Crohn's disease, since the drug became available in routine health care. All patients had previously over long time periods tried several different treatments without obtaining stable symptom control. Information on the severity of disease, symptoms, laboratory tests, examinations performed, outcome and length of treatment and need for surgical interventions was retrieved from the medical records and further analyzed with statistical methods. What did the researchers find? Of all 322 patients 31% stopped the treatment within the first year, most often due to lack of stable symptom control or side effects. Less than one of 100 patients had to undergo surgery. More than half of all patients continued the treatment for at least one year and one-third for at least two years. Laboratory tests and endoscopic examinations used to assess ongoing inflammation improved. What do the findings mean? This study provides reliable information on the routine use of ustekinumab in patients with Crohn's disease and persisting disease symptoms despite several previous treatments attempts. More than half of these difficult-to-treat patients had long-term benefit of this biologic and the drug was most often well tolerated.
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Background: The association of stress and acute coronary events has been extensively explored. An increased output of catecholamines leading to high blood pressure and alteration of hemostasis may be responsible for this effect. A severe earthquake and tsunami is a major stress. Methods and Results. 280,592 electrocardiograms (ECG) obtained via a telemedicine system in the years 2009 and 2010 were analyzed. The frequency of subepicardial lesions recorded during the weekend in which the earthquake took place (27/2/2010 - 28/2/2010) was compared to that observed in all other weekends throughout the period. 7 subjects had a blood pressure Holter monitoring on that weekend. A subepicardial lesion was diagnosed in 0.64% of ECGs recorded throughout the period, increasing significantly in the earthquake's weekend (p<0.05). The age distribution of subepicardial lesions was similar in all weekends. However, the higher proportion of males with sub epicardial lesions throughout the study period changed to a higher proportion of females in the earthquake's weekend. Significant increases in blood pressure and heart rate were observed in coincidence with the earthquake in patients undergoing blood pressure monitoring. Conclusion: a statistically significant increase in subepicardial lesions demonstrated by telemedicine ECG recordings was associated to the stressful situation of the 2010 earthquake in Chile.
La asociación de estrés y eventos coronarios agudos ha sido extensamente estudiada. En relación a un evento estresante existiría un aumento en la liberación de ca-tecolaminas que incide en un incremento en la presión arterial y alteraciones de hemostasia, como sería el caso de un terremoto. En el presente trabajo se describe la relación contemporánea observada entre el terremoto del 27 de febrero del 2010 y el diagnóstico de lesión subepicárdica, en electrocardiogramas recibidos en ITMS, Telemedicina de Chile. Se analizaron 280.592 electrocardiogramas (ECGs) provenientes de todo el territorio nacional, que corresponden a un periodo de 12 meses de los años 2009 y 2010. Se realizó una comparación estadística entre el porcentaje de lesiones subepicárdicas registradas en el fin de semana del terremoto (27/02/2010 y 28/02/2010) versus los fines de semana de los meses estudiados. Se obtuvieron los datos correspondientes a siete pacientes que se encontraban con monitoreo ambulatorio de presión arterial (MAPA) el día 27/02. El diagnóstico de lesión subepicárdica se hizo en 1.795 trazados, correspondientes a un 0.64% del total de ECGs recibidos. Hubo un aumento estadísticamente significativo de las lesiones subepicárdicas (p<0,05) en el fin de semana del terremoto, la distribución por edad se mantuvo similar al resto de los períodos analizados. Sin embargo se invirtió la distribución por género durante dicho fin de semana siendo mayor en mujeres que en hombres, como es en el resto de los períodos analizados. En los registros MAPA se documentó un aumento de la presión arterial y frecuencia cardíaca en relación al evento estresante. Se confirmó entonces un aumento estadísticamente significativo del diagnóstico electrocardiográfico de lesiones subepicárdicas en relación al estrés producido por el terremoto del 27 de febrero de 2010.