Small Bowel Crohn's Disease Recurrence is Common After Total Proctocolectomy for Crohn's Colitis.

BACKGROUND: Surgical intervention for Crohn's disease involving the colon is often a total proctocolectomy with end ileostomy. There are limited data regarding postoperative small bowel recurrence rates in the recent era. OBJECTIVE: The purpose of this study was to determine the rate of small bowel Crohn's disease recurrence following total proctocolectomy and secondarily define risk factors for disease recurrence. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at four hospitals within a single healthcare system. PATIENTS: Patients were those with Crohn's disease undergoing total proctocolectomy with end ileostomy between 2009-2019. MAIN OUTCOME MEASURES: Main outcome measures were clinical, endoscopic, radiographic, and/or surgical Crohn's disease recurrence. RESULTS: In total, 193 patients were included with a median follow-up of 1.8 years (IQR 0.4-4.6). Overall, 74.6% (n = 144) of patients had been previously exposed to biologic therapy, and 51.3% (n = 99) had a history of small bowel Crohn's disease. Postoperatively, 14.5% (n = 28) of patients received biologic therapy. Crohn's disease recurrence occurred in 23.3% (n = 45) of patients with an estimated median 5-year recurrence rate of 40.8% (95% CI' 30.2-51.4). Surgical recurrence occurred in 8.8% (n = 17) of patients with an estimated median 5-year recurrence rate of 16.9% (95% CI' 8.5-25.3). On multivariable analysis, prior small bowel surgery for Crohn's disease (HR 2.61; 95% CI' 1.42-4.81) and Crohn's diagnosis at age <18 years (HR 2.56; 95% CI' 1.40-4.71) were associated with Crohn's recurrence. In patients without prior small bowel Crohn's disease, 14.9% (n = 14) had Crohn's recurrence with an estimated 5-year overall recurrence rate of 31.1% (95% CI' 13.3-45.3) and 5-year surgical recurrence rate of 5.7% (95% CI' 0.0-12.0). LIMITATIONS: The study was limited by its retrospective design and lack of consistent follow-up on all patients. CONCLUSIONS: Greater than one third of patients who underwent total proctocolectomy for Crohn's disease were estimated to have small bowel Crohn's recurrence at 5 years after surgery. Patients with a history of small bowel surgery for Crohn's and diagnosis at any early age may benefit from more intensive postoperative surveillance and consideration for early medical prophylaxis. See Video Abstract at http://links.lww.com/DCR/B762. RECURRENCIA FRECUENTE DE LA ENFERMEDAD DE CROHN DEL INTESTINO DELGADO DESPUS DE LA PROCTOCOLECTOMA TOTAL POR COLITIS DE CROHN: ANTECEDENTES:La cirugia para la enfermedad de Crohn que involucra el colon es a menudo una proctocolectomía total con ileostomía terminal. Hay datos limitados con respecto a las tasas de recurrencia posoperatoria de la enfermedad de Crohn del intestino delgado en la actualidad.OBJETIVO:Buscamos determinar la tasa de recurrencia de la enfermedad de Crohn del intestino delgado después de la proctocolectomía total y, en segundo lugar, definir los factores de riesgo de recurrencia de la enfermedad.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:Cuatro hospitales de un mismo sistema sanitario.PACIENTES:Pacientes con enfermedad de Crohn sometidos a proctocolectomía total con ileostomía terminal entre 2009-2019.PRINCIPALES MEDIDAS DE VALORACIÓN:Recurrencia clínica, endoscópica, radiográfica y / o quirúrgica de la enfermedad de Crohn.RESULTADOS:Se incluyeron 193 pacientes con un seguimiento promedio de 1,8 años (IQR 0,4-4,6). El 74,6% (n = 144) de los pacientes habían recibido previamente terapia biológica y el 51,3% (n = 99) tenían antecedentes de enfermedad de Crohn del intestino delgado. Después de la operación, el 14,5% (n = 28) de los pacientes recibieron terapia biológica. La recurrencia de la enfermedad de Crohn ocurrió en el 23,3% (n = 45) de los pacientes con una tasa de recurrencia media estimada a los 5 años del 40,8% (IC del 95%: 30,2-51,4). La recidiva quirúrgica se produjo en el 8,8% (n = 17) de los pacientes con una tasa de recidiva media estimada a los 5 años del 16,9% (IC del 95%: 8,5-25,3). En el análisis multivariable, la cirugía previa del intestino delgado para la enfermedad de Crohn (HR 2,61, IC del 95%: 1,42-4,81) y el diagnóstico de Crohn a la edad <18 (HR 2,56, IC del 95%: 1,40-4,71) se asociaron con la recurrencia de Crohn. En pacientes sin enfermedad previa de Crohn del intestino delgado, el 14,9% (n = 14) tuvo recurrencia de Crohn con una tasa de recurrencia general estimada a 5 años del 31,1% (IC del 95%: 13,3-45,3) y una tasa de recurrencia quirúrgica a 5 años del 5,7% (IC del 95%: 0,0-12,0).LIMITACIONES:Diseño retrospectivo, falta de seguimiento constante de todos los pacientes.CONCLUSIONES:Se estimó que más de un tercio de los pacientes que se sometieron a proctocolectomía total tenían recurrencia de Crohn del intestino delgado a los 5 años después de la cirugía. Los pacientes con antecedentes de cirugía por enfermedad de Crohn del intestino delgado y diagnóstico a una edad temprana pueden beneficiarse de una vigilancia posoperatoria más intensiva y la consideración de una profilaxis médica temprana. Consulte Video Resumen en http://links.lww.com/DCR/B762. (Traducción- Dr. Ingrid Melo).

Encuesta de satisfacción de tratamientos biológicos en un hospital comarcal / Survey of satisfaction of biological treatments in a regional hospital

No disponible

Decreasing major surgical rates for Crohn's disease in an emerging economy over two decades: Is it due to biologic therapy?

BACKGROUND: Alteration in the natural history of Crohn's disease (CD) since the advent of biologic therapy remains to be proven. Our aim was to look at the intestinal surgical rates and the association with biologic therapy over the last two decades. METHODS: This was a retrospective study in which all CD patients seen in two tertiary referral hospitals in Malaysia were recruited. Patients were stratified into two cohorts; cohort 1 was patients diagnosed from year 1991 to 2000 and cohort 2 was patients diagnosed from year 2001 to 2010. These time cohorts were selected based on initial availability of biologic agents in Malaysia in year 2000. Details of demography, disease location, medications and cumulative surgical rates over 7 years were recorded. RESULTS: A total of 207 patients were recruited: 70 from cohort 1 and 137 from cohort 2. Differences seen in terms of disease location, phenotype, and use of immunomodulatory therapy between the two cohorts were not significant. Patients who were ever exposed to biologics were significantly different between the two cohorts, approximately two times higher at 35.8% (n = 49) in cohort 2, and 18.6% (n = 13) in cohort 1, p = 0.011. There was a significant reduction in the 7-year cumulative intestinal surgical rates between cohort 1 and cohort 2, from 21.4% (n = 15) to 10.2% (n = 14), p = 0.028. However, there was no statistically significant difference in biologic exposure between those who underwent surgery and those who did not. CONCLUSIONS: There has been a significant reduction in intestinal surgical rates for Crohn's disease over the last two decades but does not appear to be associated with the increased use of biologics.

[Biotherapies in elderly patients]. / Biothérapies chez le sujet âgé.

The ageing of the population leads health professionals to question the tolerance and the effectiveness of the different biotherapies used in autoimmune diseases. Due to the exponential increase of biotherapies and their indications, several studies have been carried out to evaluate their impact on elderly patients suffering from autoimmune disease. However, these studies are still too few to take into account all the different specificities of elderly patients and their comorbidities; prescribers are therefore hesitant with their introduction after 75 years or even 65. More than the age of patients, it is necessary to evaluate the comorbidities before introducing this kind of treatments. Every biotherapy has different indications and contraindications, which must be known to adapt each treatment to each patient. This focus aims to remind of the adaptations and contraindications of the different biological disease-modifying anti-rheumatic drugs for geriatric population, and improve their uses since the treatments for these patients are sometimes not enough. Here we resume the methods allowing supervisors to identify errors of clinical reasoning in medical students and interns and we explain remediation techniques adapted to the types of error identified. Access to short illustrative videos of a MOOC (Massive Open On line Course) devoted to the supervision of clinical reasoning constitutes practical help for supervisors who are not expert in the complexity of medical pedagogy at the bedside.

A Six-Year Analysis of Biological Therapy for Severe Psoriasis in a Lithuanian Reference Centre of Dermatovenereology.

Background and Objectives: Biological therapy is widely used for the treatment of severe psoriasis. The objective of this study was to evaluate the efficacy and safety of biological therapy for patients with severe psoriasis. Materials and Methods: A retrospective study of 79 patients with severe psoriasis, who have been treated with biological therapy between 2012 and 2018, was conducted. During this study, the following data were collected and evaluated: sex, age, body mass index (BMI), duration of illness, the results of treatment with biological therapy, concomitant therapy, Psoriasis Area and Severity Index (PASI) and adverse events. Results: In total, 74.7% (n = 59) of subjects were male. Their overall average age was 47.4 ± 11.4 (range: 18-73) years. Their baseline BMI was 27.6 ± 5.9, which increased to 29.6 ± 4.5 after 6 years of treatment. The mean duration of psoriasis was 25.7 ± 12.5 years. In total, 39.2% (n = 31) of subjects received infliximab, 36.7% (n = 29)-etanercept, 24.1% (n = 19)-ustekinumab. The treatment duration for infliximab, etanercept and ustekinumab was 201.6 ± 86.8, 156.2 ± 137.4 and 219.1 ± 95.7 weeks (p < 0.01), respectively. Overall, 65.8% (n = 52) of subjects were also on methotrexate; 30.8% (n = 16) of them discontinued it due to clinical improvement (31.3% (n = 5)), impaired liver function (31.3% (n = 5)), and intolerance (25% (n = 4)). Baseline PASI was 20.8 ± 8.8. PASI 50 was achieved by 96.2% (n = 76) of patients at week 11, PASI 75 by 86.1% (n = 68) at week 16, PASI 90 by 54.4% (n = 43) at week 35, and PASI 100 by 13.9% (n = 11) at week 33. The overall incidence rate of adverse events was 0.362 per patient year of follow-up. Conclusion: Biological therapy is an effective and safe treatment for patients with severe psoriasis.

What's new in atopic eczema? An analysis of systematic reviews published in 2018. Part 2: systemic therapies.

This review forms part of an annual update series on atopic eczema (AE), where systematic reviews (SRs) are gathered and appraised to provide a summary of key recent research findings. The focus of this article is systemic therapies used in AE, while a review on prevention and topical therapies is provided in Part 1. In total, 17 SRs on various systemic treatments used in AE were first published or indexed in 2018. There is a lack of evidence to support vitamin D supplementation, montelukast and naltrexone in AE treatment. The adverse effects of systemic corticosteroids are the main barrier to their use, and there is also a lack of data to determine the optimal delivery and duration of treatment with them. Of other immunosuppressants, ciclosporin has the most robust evidence of efficacy. Biologic therapies in AE treatment are being increasingly investigated, and to date, the greatest quantity of data and evidence of efficacy relates to dupilumab. The most commonly reported adverse effects are injection-site reactions and conjunctivitis. Other biologics showing some evidence of efficacy include nemolizumab, lebrikizumab and tralokinumab, although further data are needed. There are currently insufficient data on oral small molecules, including Janus kinase inhibitors, in the treatment of AE. A Cochrane review on probiotics showed no significant benefit, and SRs and meta-analyses on complementary and alternative medicines, including probiotics, in paediatric AE demonstrated significant heterogeneity, thereby limiting their interpretation. This summary of recent SRs provides up-to-date evidence for clinicians on systemic therapies in AE.

The landscape of psoriasis provision in the UK.

Psoriasis remains one of the commonest conditions seen in dermatological practice, and its treatment is one of the greatest cost burdens for the UK National Health Service. Treatment of psoriasis is complex, with numerous overlapping lines and therapies used in combination. This complexity reflects the underlying pathophysiology of the disease as well as the heterogeneous population that it affects. National Institute for Health and Care Excellence (NICE) guidance for the treatment of psoriasis has been available since 2013, and has been the subject of three national audits conducted by the British Association of Dermatologists. This report synthesizes the results of the most recent of those exercises and places it in the context of the NICE guidance and previous audits. It clearly shows the significant burden of disease, issues with provision of services and long waiting times and the marked shift in therapies towards targeted biologic therapies.

Systematic review with meta-analysis: biologics and risk of infection or cancer in elderly patients with inflammatory bowel disease.

BACKGROUND: Uncertainty exists concerning the risk of infection and cancer associated with biologic therapies in elderly patients with inflammatory bowel disease (IBD). AIMS: To identify, synthesise and critically appraise the available evidence on the topic. METHODS: We systematically searched Medline/PubMed, Embase and Scopus, through October 2019, and recent conference proceedings, to identify studies investigating the risk of serious infections, opportunistic infections, any infection and cancer in elderly IBD patients (>60 years) exposed to biologics as compared to those unexposed to biologics. Two reviewers independently extracted study data and assessed each study's risk of bias. We examined heterogeneity, and calculated summary effect estimates using fixed- and random effects models. Quality of evidence was determined with GRADE. RESULTS: We included 15 studies (one post hoc analysis of a randomised trial, nine cohort and five case-control studies). Elderly IBD patients treated with biologics were at increased risk of developing serious infections (random effects summary relative risk: 2.70, 95% CI: 1.56-4.66; seven studies; I2  = 57%) and opportunistic infections (3.16, 1.09-9.20; four studies; I2  = 73%). The occurrence of any infection (1.67, 0.51-5.43; five studies; I2  = 75%) and cancer (0.90, 0.64-1.26; nine studies; I2  = 0%) was not significantly affected. Nevertheless, our confidence in the effect estimates is rather limited; the quality of evidence is low to very low. CONCLUSIONS: Biologics are likely to increase the risk of serious and opportunistic infections in old IBD patients. Large prospective studies are needed to further assess the biologic treatments' long-term safety profile in this population.

Predicting response to anti-TNFα therapy among patients with axial spondyloarthritis (axSpA): results from BSRBR-AS.

OBJECTIVES: While many axSpA patients, eligible to receive anti-TNFα therapy, derive benefit when prescribed them, some patients do not. The current study aims to identify modifiable targets to improve outcome as well as non-modifiable targets that identify groups less likely to derive benefit. METHODS: The BSRBR-AS is a prospective cohort study of axSpA patients who, at recruitment, were naïve to biologic therapy. Those in the 'biologic' sub-cohort commenced their first anti-TNFα therapy at recruitment or during follow-up. Prior to commencement, information was collected on socio-economic, clinical and patient-reported factors. Outcome was assessed according to ASAS20, ASAS40, ASDAS reduction and achieving a moderate/inactive ASDAS disease state. RESULTS: 335 participants commenced their first anti-TNFα therapy and were followed up at a median of 14 (inter-quartile range 12-17) weeks. Response varied between 33% and 52% according to criteria used. Adverse socio-economic factors, fewer years in education predicted lower likelihood of response across outcome measures as did not working full-time. Co-morbidities and poor mental health were clinical and patient-reported factors, respectively, associated with lack of response. The models, particularly those using ASDAS, were good at predicting those who did not respond (negative predictive value (NPV) 77%). CONCLUSION: Some factors predicting non-response (such as mental health) are modifiable but many (such as social/economic factors) are not modifiable in clinic. They do, however, identify patients who are unlikely to benefit from biologic therapy alone. Priority should focus on how these patients receive the benefits that many derive from such therapies.

Pregnant women with IBD are more likely to be adherent to biologic therapies than other medications.

BACKGROUND: There are differences in the efficacy and safety profiles of medications used to treat IBD that may impact a woman's perceived risk of medication exposure during pregnancy, potentially leading to medication non-adherence, poor disease-control and adverse pregnancy outcomes. AIM: To assess whether medication adherence patterns differ by drug class during pregnancy and influence birth outcomes for women with IBD. METHODS: Of 143 491 women, a validated case definition was used to identify 370 women with IBD in five administrative health databases in Alberta, Canada (2012-2015). Women who had ≥2 consecutive medications prescription for maintenance therapy for IBD in the year prior to pregnancy were included (n = 230). Prescription-based medication possession ratio ≥0.8 defined adherence. Chi-squared tests were used to compare adherence patterns by drug class and outcomes. RESULTS: Of the 159/230 women who were adherent during the year prior to pregnancy, 20 (12.6%; 95% CI: 8.2%, 18.8%) were not adherent and 21 (13.2%; 95% CI: 8.7%, 19.5%) discontinued their medications during pregnancy. Medication adherence during pregnancy differed significantly by drug class. A greater proportion of women on biologics (41.5%; 95% CI 32.9%, 50.7%) were adherent during pregnancy than women on thiopurines (22.9%; 95% CI 16.1%, 31.5%; P = 0.006); adherence was not significantly different for 5-aminosalicylates (35.6%; 95% CI 27.4%, 44.8%; P = 0.204). Women were more likely to be adherent to biologics (49.3%, 95% CI 37.3%, 61.3%) than thiopurines (20.9%; 95% CI 12.6%, 32.6%; P = 0.014) and 5-aminosalicylates (29.9%; 95% CI 19.9%, 42.1%; P = 0.030) in the first trimester. This was similar in the third trimester. In the second trimester, adherence pattern did not significantly differ by drug class (biologics vs thiopurines: P = 0.348; biologics vs 5-aminosalicylate: P = 0.999). Infants born to women with IBD (adherent: RR 1.58. 95% CI 1.02, 2.27; non-adherent: RR 1.32, 95% CI 0.97, 1.81) were more likely to be admitted into the neonatal intensive care unit than the general obstetric population, but this was not significantly different between women who were adherent or not adherent to their IBD medication (P = 0.711). CONCLUSION: Almost a quarter of women with IBD who were previously adherent to medical therapy were not adherent during pregnancy. Adherence pattern differed by drug class.

Adherence to biological therapies in patients with chronic inflammatory arthropathies.

INTRODUCTION: The aims of the study were to quantify adherence, determine the factors that can  predict adherence and identify the consequences of poorer adherence in patients with chronic  inflammatory arthropathies treated with biological therapies in daily clinical practice. METHOD: A descriptive, observational and retrospective study was carried out. Patients with  rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who started a biologic therapy  between 1 January 2009 and 31 December 2016 were included. Variables related to socioeconomic  status, the disease, the biological therapy and hospital resources were included. Adherence was  calculated by using the medication possession ratio. RESULTS: Three hundred and sixty-two patients and 423 lines of biological therapy were included.  Mean age ± standard deviation was 50.3 ± 13.9 years, and 228 (53.9%) were women. The  percentage of adherent patients was 187 out of 216 (87%) in rheumatoid arthritis, 91 out of 107  (85%) in ankylosing spondylitis and 84 out of 100 (84%) in psoriatic arthritis. Greater adherence was  associated with more frequent visits to the pharmacy service (odds ratio 1.2, 95% confidence  interval: 1.1-1.3 [p = 0.001]) and poorer adherence with a failure to attend scheduled appointments  at the rheumatology clinic (odds ratio 0.2, 95% confidence interval: 0.1-0.9 [p = 0.030]). There were  no differences between  adherent and non-adherent patients in terms of the number of hospital resources used. CONCLUSIONS: There are no differences in adherence to biological therapies among patients with  chronic inflammatory arthropathies. Adherence correlates with attendance at outpatient  appointments, but this does not imply an increase in the use of hospital resources.

Objetivo: Los objetivos del estudio fueron cuantificar la adherencia, determinar los factores  predictivos y conocer las consecuencias de una menor adherencia, en la práctica clínica diaria, en  pacientes con artropatías inflamatorias crónicas tratados con terapias biológicas. Método: Estudio descriptivo, observacional y retrospectivo. Se incluyeron pacientes con artritis  reumatoide, espondilitis anquilosante y artritis psoriásica que iniciaron una terapia biológica entre el 1  de enero de 2009 y el 31 de diciembre de 2016. Se recogieron variables sociodemográficas, relacionadas con la enfermedad, sobre las terapias biológicas y los recursos  hospitalarios. La adherencia se calculó mediante la ratio media de posesión.Resultados: Se incluyeron 362 pacientes y 423 líneas de terapia biológica. La media de edad ±  desviación estándar fue de 50,3 ± 13,9 años; 228 (53,9%) fueron mujeres. El porcentaje de  adherentes fue de 187 de 216 (87%) en artritis reumatoide, 91 de 107 (85%) en espondilitis  anquilosante y 84 de 100 (84%) en artritis psoriásica. La adherencia se relacionó con acudir con más  frecuencia a la consulta del servicio de farmacia(odds ratio de 1,2; intervalo de confianza 95%: 1,1- 1,3 [p = 0,001]) e inversamente con no acudir a las consultas de reumatología en la fecha prevista (odds ratio de 0,2; intervalo de confianza 95%: 0,1-0,9 [p = 0,030]). No hubo diferencias en  el número de recursos hospitalarios utilizados por pacientes adherentes y no adherentes.Conclusiones: La adherencia a las terapias biológicas entre las artropatías inflamatorias crónicas es  similar. Dicha adherencia se correlaciona con la frecuentación a consultas externas, pero no implica  un aumento del consumo de recursos.

[Use of biotherapy in the management of Behçet's disease in a department of internal medicine]. / Recours à la biothérapie dans la prise en charge de la maladie de Behçet dans un service de médecine interne.

BACKGROUND: Behçet's disease (BD) is a recurrent multisystemic disease responsible for occlusive vasculitis with arterial, venous and capillary involvement. The aim of this study was to determine the frequency and the features associated with the use of biotherapy in the management of patients followed in our department for BD. METHODS: This is a retrospective study of patients medical records followed for BD in a department of internal medicine from January 2005 to August 2018. RESULTS: A total of 41 patients were included with a mean age at diagnosis of 42.5±12.1 years (range 16 to 63) and a sex ratio men/women of 1.05. Oral and/or genital aphtosis was present in 70.7% of the patients. Other lesions were: ocular (78.0%), articular (46.3%), cutaneous (41.5%), central neurological (34.1%), vascular (26.8%), digestive (7.3%), pericardial (2.4%) and epididymal (2.4%). A biotherapy, interferon α and monoclonal antibodies, was used in 15 patients (36.6%), after failure of conventional treatments. The monoclonal antibodies were anti-TNFα (infliximab, adalimumab, certolizumab and golimumab) except in one patient for whom ustekinumab was used. Biotherapy was used in 46.9% of the patients with ocular involvement and never used in those patients without ocular involvement (P=0.01). CONCLUSION: Biotherapy is effective and represents a solution to the failures of conventional treatments in severe forms of Behçet's disease with ocular involvement.

Autologous Blood Patch Injection versus Hydrogel Plug in CT-guided Lung Biopsy: A Prospective Randomized Trial.

Purpose To compare the effect of autologous blood patch injection (ABPI) with that of a hydrogel plug on the rate of pneumothorax at CT-guided percutaneous lung biopsy. Materials and Methods In this prospective randomized controlled trial ( https://ClinicalTrials.gov , NCT02224924), a noninferiority design was used for ABPI, with a 10% noninferiority margin when compared with the hydrogel plug, with the primary outcome of pneumothorax rate within 2 hours of biopsy. A type I error rate of 0.05 and 90% power were specified with a target study population of 552 participants (276 in each arm). From October 2014 to February 2017, all potential study participants referred for CT-guided lung biopsy (n = 2052) were assessed for enrollment. Results The data safety monitoring board recommended the trial be closed to accrual after an interim analysis met prespecified criteria for early stopping based on noninferiority. The final study group consisted of 453 participants who were randomly assigned to the ABPI (n = 226) or hydrogel plug (n = 227) arms. Of these, 407 underwent lung biopsy. Pneumothorax rates within 2 hours of biopsy were 21% (42 of 199) and 29% (60 of 208); chest tube rates were 9% (18 of 199) and 13% (27 of 208); and delayed pneumothorax rates within 2 weeks after biopsy were 1.4% (three of 199) and 1.5% (three of 208) in the ABPI and hydrogel plug arms, respectively. Conclusion Autologous blood patch injection is noninferior to a hydrogel plug regarding the rate of pneumothorax after CT-guided percutaneous lung biopsy. © RSNA, 2018 Online supplemental material is available for this article.

Regional differences in anti-TNF-α therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study.

BACKGROUND AND AIMS: During the last decades, substantial progress has been made in both medical and surgical treatment of inflammatory bowel disease (IBD). The aim of this study was to determine the use of anti-TNFs and surgery during the first 3 years after diagnosis in IBD patients across the four health regions in Norway using nationwide patient registry data. METHODS: This study used nationwide data from the Norwegian Patient Registry. Cumulative incidence of anti-TNF exposure and major surgery was calculated for patients diagnosed in 2010-2012. The analyses were stratified by diagnosis and health region. All patients were followed for an equal period of 3 years from diagnosis. RESULTS: The study population included 8,257 IBD patients first registered between 2010 and 2012, of whom 2,829 were diagnosed with Crohn's disease (CD) and 5,428 with ulcerative colitis (UC). Across Norway's health regions, the cumulative incidence of major surgery after 3 years varied from 11.4% to 17.1% for CD and from 4.6% to 6.9% for UC. The cumulative incidence of anti-TNF exposure varied from 20.9% to 31.4% for CD and from 8.0% to 13.5% for UC. The region with the lowest anti-TNF use had the highest surgery rates for both UC and CD. CONCLUSIONS: Cumulative incidence of anti-TNF exposure and surgery varied significantly across Norway's health regions during the three first years after IBD diagnosis.

Persistence rates and medical costs of biological therapies for psoriasis treatment in Japan: a real-world data study using a claims database.

BACKGROUND: Biological therapies (BTs) including infliximab (IFX), adalimumab (ADL), secukinumab (SCK) and ustekinumab (UST) are approved in Japan for the treatment of psoriasis. Although the persistence rates and medical costs of BTs treatment have been investigated in multiple foreign studies in recent years, few such studies have been conducted in Japan and the differences between patients who adhered to treatment and those who did not have not been reported. This study is aimed at investigating the persistence rates and medical costs of BTs in the treatment of psoriasis in Japan, using the real-world data from a large-scale claims database. METHODS: Claims data from the JMDC database (August 2009 to December 2016) were used for this analysis. Patient data were extracted using the ICD10 code for psoriasis and claims records of BT injections. Twelve-month and 24-month persistence rates of BTs were estimated by Kaplan-Meier methodology, and 12-month-medical costs before and after BT initiation were compared between persistent and non-persistent patient groups at 12 months. RESULTS: A total of 205 psoriasis patients treated with BTs (BT-naïve patients: 177) were identified. The 12-month/24-month persistence rates for ADL, IFX, SCK, and UST in BT-naïve patients were 46.8% ± 16.6%/46.8 ± 16.6%, 53.0% ± 14.9%/41.0% ± 15.5%, 55.4%/55.4% (95% CI not available) and 79.4% ± 9.9%/71.9% ± 12.2%, respectively. Statistically significant differences in persistence were found among different BT treatments, and UST was found to have the highest persistence rate. The total medical costs during the 12 months after BT initiation in BT-naïve patients were (in 1000 Japanese Yen): 2218 for ADL, 3409 for IFX, 465 for SCK, 2824 for UST (average: 2828). Compared with the 12-month persistent patient group, the total medical costs in the persistent group was higher (Δ:+ 118), but for some medications such as IFX or UST cost increases were lower for persistent patients. CONCLUSIONS: UST was found to have the highest persistence rate among all BTs for psoriasis treatment in Japan. The 12-month medical costs after BT initiation in the persistent patient group may not have increased as much as in the non-persistent patient group for some medications.

Marco legal europeo y español para el desarrollo de las terapias avanzadas y herramientas regulatorias y legales impulsadas a nivel internacional para facilitar el acceso de los pacientes / European and Spanish legal framework for the development of advanced therapies and regulatory and legal tools promoted at international level to facilitate patient access

El marco regulatorio de los medicamentos de terapias avanzadas (terapia celular somática, terapia génica, ingeniería de tejidos y combinados con productos sanitarios) se caracteriza por su singularidad debido a la complejidad en el desarrollo de estos medicamentos poniéndose de manifiesto en el escaso número que han alcanzado una autorización de comercialización. En Europa, al igual que en múltiples países de otros continentes, se han puesto en marcha diferentes medidas regulatorias y legales para intentar facilitar el acceso de los pacientes a estas terapias cuya principal barrera, más allá de la dificultad logística que conllevan, se encuentra en los elevados precios que alcanzan en el mercado

The legal framework of Advanced Therapy Medicinal Products (somatic cell therapy, gene therapy, tissue engineering and combined products with medical devices) is singular due to the complexity of the development of these products resulting in few medicines granted marketing authorization. In Europe, as well as in other countries from different continents, several legal and regulatory measures have been put in place to facilitate patients' accessibility to these medicinal products. Beyond the logistic challenge that ATMPs pose, the high price of marketed products represents a major barrier for accessibility

High rate of serious infection in juvenile idiopathic arthritis patients under biologic therapy in a real-life setting.

OBJECTIVES: To assess the rate of serious and/or opportunistic infections in juvenile idiopathic arthritis (JIA) patients from a single tertiary center under biologic therapy and to identify possible risk factors associated to these complications. METHODS: A total of 107 JIA patients followed at the biologic therapy center of our tertiary university hospital using a standardized electronic database protocol including demographic data, clinical and laboratorial findings and treatment at baseline and at the moment of infection. Opportunistic infections included tuberculosis, herpes zoster and systemic mycosis. RESULTS: A total of 398 patient-yrs(py) were included. The median time of biologic exposure was 3.0 years (0.15-11.5). We observed 35 serious/opportunistic infectious events in 27 (25%) patients: 31(88.6%) were serious infections and four (11.4%) opportunistic infections. Serious/opportunistic infections rates were 10.6/100py for ETN, 10.9/100py for ADA, 2.6/100py for ABA and 14.8/100py for TCZ. Comparison of 27 patients with and 80 without infection showed a higher frequency of systemic-onset JIA, lower age at biologic therapy initiation and a history of previous serious infection (p < .05) in the former group. CONCLUSIONS: This study demonstrated a high rate of serious infections in JIA patients under biologic therapy in a real-life setting. Systemic-onset JIA, lower age at biologic therapy start and history of previous serious infections were important risk factors for these complications. Also, higher rates of severe infections comparing to the former studies was possibly due to elevated MTX doses in our patients.

Persistency of Biologic Therapies for Plaque Psoriasis in 2 Large Community Practices.

BACKGROUND: Biologics have transformed the management of moderate to severe psoriasis. The persistency of biologics lacks real-world data. OBJECTIVES: To quantify drug survival of infliximab (IFX), adalimumab (ADA), etanercept (ETA), and ustekinumab (UST) and to identify potential factors affecting drug survival. METHODS: An observational, retrospective 2-centre study consisting of 906 patients from private practices in Ontario between July 2003 and June 13, 2016, was conducted, including patients with plaque psoriasis receiving commercial treatment with ADA, ETA, IFX, and UST. Paper and electronic records of each patient were reviewed. RESULTS: Median survival times for UST, IFX, ADA, and ETA were respectively, in months, 68, 23, 33, and 28. Female sex was determined to be a statistically significant positive predictor of drug survival. Our study was consistent with the literature in that UST had the highest survival rate compared to the other biologics, and the shape of our drug survival curve suggested that loss of drug efficacy is a stochastic occurrence. Compared to other studies, our data exhibited lower survival rates at various time points for all the biologics studied, and female sex did not predict drug survival in other studies. We also investigated potential reasons for differences in biologic survival times between different practices; the main differentiator was drug dosage, as higher dosages were associated with greater survival. CONCLUSION: UST has a higher drug survival rate than ADA, ETA, and IFX, as observed in other studies. When practice patterns are compared, dosage difference is the main factor that may cause differing survival rates.

Market share and costs of biologic therapies for inflammatory bowel disease in the USA.

BACKGROUND: Real-world data quantifying the costs of increasing use of biologics in inflammatory bowel disease (IBD) are unknown. AIM: To determine the outpatient IBD drug utilization trends, relative market share, and costs in the USA during a 9-year period. METHODS: The Truven MarketScan® Database was analysed for patients with Crohn's disease (CD) and ulcerative colitis (UC) during 2007-2015. National drug codes were used to identify prescription drugs; Healthcare Common Procedure Coding System J-codes were used to capture biologic out-patient infusions. Proportion of drug usage, relative market share and per-member per-year (PMPY) costs were analysed for biologics, immunomodulators, 5-ASAs and corticosteroids. RESULTS: In 415 405 patients (188 842 CD; 195 183 UC; 31 380 indeterminate colitis; 54.67% female), utilization trends show a consistent rise in the market share of biologics during the 9-year study period. The proportion of patients using biologics increased from 21.8% to 43.8% for CD and 5.1%-16.2% for UC. This contrasts a small decrease in immunomodulator and 5-ASA use for CD and relative constancy of other classes including corticosteroids-only use as primary IBD medication from 2007 to 2015. The average biologic-taking patient accounted for $25 275 PMPY in 2007 and $36 051 PMPY in 2015. The average paediatric biologic-taking patient accounted for $23 616 PMPY in 2007 and $41 109 PMPY in 2015. In all patients, the share of costs for biologics increased from 72.9% in 2007 to 85.7% in 2015 (81.7% in 2007 to 94.9% in 2015 in paediatrics). CONCLUSION: The vast majority of costs allocated to out-patient IBD medications in the USA is attributed to increasing use of biologic therapies despite the relative minority of biologic-taking patients.