Evaluation of persistence, retention "rate" and prescription pattern of original infliximab and infliximab CT-P13 in biologic-naïve patients with ulcerative colitis.

OBJECTIVE: To compare the persistence, retention rate and prescription pattern  of original infliximab and infliximab CT-P13 in biologic- naïve patients with ulcerative colitis. METHOD: This was an ambispective study of biologic-naive patients with  ulcerative colitis who received non-simultaneous first-line treatment with  Remicade ® (infliximab) and Remsima® (infliximab CT-P13) over a 10-year  study period (2012-2021). Data on their age, weight, persistence, retention  rate and on whether they required intensification or deintensification  throughout the study period was collected. The real patient/year cost of  Remicade® and Remsima® was determined individually based on the amounts  administered during the study period. RESULTS: 27 biologic-naive patients were treated with Remicade® and 53 with  Remsima®. Neither patient group presented with differences in terms of  weight and age. Persistence (median ± interquartile range) with Remicade ®  was 42.49 ± 57.48 months, as compared to 27.50 ± 58.50 months for  Remsima®, without significant differences (p = 0.455). The retention rate at  6, 12, and 24 months was 81%, 63%, and 33%, respectively, for the Remicade® group and 71%, 47%, and 37%, respectively, for the Remsima® group. Nine subjects in the Remicade® group vs 11 patients in the Remsima ® group were intensified. Regarding deintensification, five patients treated with  Remicade® were deintensified, as compared with 7 patients on Remsima®.  Savings obtained with the use of Remsima® amounted to 203,649 €, which  would allow treating an additional 118 patients with biosimilar infliximab for  one year. CONCLUSIONS: There are no significant differences in persistence, retention, and number of intensifications or deintensifications between  iologicnaïve patients treated with Remicade® and those treated with  Remsima®, the latter being an effective, safe and economical alternative for  the treatment of ulcerative colitis.

OBJETIVO: Comparar la persistencia, tasa de retención y pauta de prescripción de infliximab original e infliximab CT-P13 en pacientes naive a biológicos con colitis ulcerosa.Método: Estudio ambispectivo de pacientes naive a biológicos en colitis ulcerosa que recibieron tratamiento en primera línea con Remicade® (infliximab) y Remsima® (infliximab CT-P13) de forma no  simultánea durante un periodo de estudio de 10 años (2012-2021). Se  tomaron datos de su edad, peso, persistencia, tasa de retención y si precisó de  intensificación o desintensificación a lo largo del periodo de estudio. Se  determinó el coste paciente/año real de Remicade® y Remsima® de forma  individualizada en función de las administraciones durante el periodo del  estudio. RESULTADOS: Un total de 27 pacientes naive a biológicos fueron tratados con  Remicade® y 53 con Remsima®. Ambos grupos de pacientes no presentaron diferencias en cuanto al peso y edad. La persistencia (mediana ±  rango intercuartílico) con Remicade® fue de 42,49 ± 57,48 meses frente a  27,50 ± 58,50 meses para Remsima®, sin demostrar diferencias significativas (p = 0,455). La tasa de retención a los 6, 12 y 24 meses fue del  81%, 63% y 33%, respectivamente, para el grupo de Remicade®, y del 71%, 47% y 37%, respectivamente, para el grupo de Remsima®. En el grupo de pacientes tratados con Remicade®, 9 pacientes fueron intensificados frente a  11 pacientes en el grupo de Remsima®. En cuanto a las desintensificaciones, 5  pacientes que recibieron tratamiento con Remicade® fueron  desintensificados frente a 7 pacientes en tratamiento con Remsima®. El ahorro obtenido con el uso de Remsima® fue de 203.649 €, que equivaldría a tratar a  118 pacientes adicionales con infliximab biosimilar durante un año. CONCLUSIONES: No existen diferencias significativas en la persistencia, tasa de  retención y número de intensificaciones y desintensificaciones entre los  pacientes naive que fueron tratados con Remicade® y aquellos tratados con  Remsima®, siendo una alternativa eficaz, segura y económica en el  tratamiento biológico de la colitis ulcerosa.

Evaluación de la persistencia, tasa de retención y pauta de prescripción de infliximab original e infliximab CT-P13 en pacientes naive biológicos con colitis ulcerosa / Evaluation of persistence, retention “rate” and prescription pattern of original infliximab and infliximab CT-P13 in biologic-naïve patients with ulcerative colitis

Objetivo: Comparar la persistencia, tasa de retención y pauta de prescripción de infliximab original e infliximab CT-P13 en pacientes naive abiológicos con colitis ulcerosa.Método: Estudio ambispectivo de pacientes naive a biológicos en colitis ulcerosa que recibieron tratamiento en primera línea con Remicade®(infliximab) y Remsima® (infliximab CT-P13) de forma no simultánea duranteun periodo de estudio de 10 años (2012-2021). Se tomaron datos de suedad, peso, persistencia, tasa de retención y si precisó de intensificacióno desintensificación a lo largo del periodo de estudio. Se determinó elcoste paciente/año real de Remicade® y Remsima® de forma individualizada en función de las administraciones durante el periodo del estudio.Resultados: Un total de 27 pacientes naive a biológicos fueron tratadoscon Remicade® y 53 con Remsima®. Ambos grupos de pacientes no presentaron diferencias en cuanto al peso y edad. La persistencia (mediana ± rangointercuartílico) con Remicade® fue de 42,49 ± 57,48 meses frente a27,50 ± 58,50 meses para Remsima®, sin demostrar diferencias significati vas (p = 0,455). La tasa de retención a los 6, 12 y 24 meses fue del 81%,63% y 33%, respectivamente, para el grupo de Remicade®, y del 71%,47% y 37%, respectivamente, para el grupo de Remsima®. En el grupo depacientes tratados con Remicade®, 9 pacientes fueron intensificados frentea 11 pacientes en el grupo de Remsima®. En cuanto a las desintensificaciones, 5 pacientes que recibieron tratamiento con Remicade® fueron desintensificados frente a 7 pacientes en tratamiento con Remsima®. El ahorroobtenido con el uso de Remsima® fue de 203.649 €, que equivaldría atratar a 118 pacientes adicionales con infliximab biosimilar durante un año. (AU)

Objective: To compare the persistence, retention rate and prescription pattern of original infliximab and infliximab CT-P13 in biologic-naïvepatients with ulcerative colitis.Method: This was an ambispective study of biologic-naive patients withulcerative colitis who received non-simultaneous first-line treatment with Remicade® (infliximab) and Remsima® (infliximab CT-P13) over a 10-year studyperiod (2012-2021). Data on their age, weight, persistence, retention rateand on whether they required intensification or deintensification throughoutthe study period was collected. The real patient/year cost of Remicade®and Remsima® was determined individually based on the amounts administered during the study period.Results: 27 biologic-naive patients were treated with Remicade® and53 with Remsima®. Neither patient group presented with differences in termsof weight and age. Persistence (median ± interquartile range) with Remicade® was 42.49 ± 57.48 months, as compared to 27.50 ± 58.50 monthsfor Remsima®, without significant differences (p = 0.455). The retention rate at 6, 12, and 24 months was 81%, 63%, and 33%, respectively, for theRemicade® group and 71%, 47%, and 37%, respectively, for the Remsima®group. Nine subjects in the Remicade® group vs 11 patients in the Remsima® group were intensified. Regarding deintensification, five patientstreated with Remicade® were deintensified, as compared with 7 patientson Remsima®. Savings obtained with the use of Remsima® amounted to203,649 €, which would allow treating an additional 118 patients withbiosimilar infliximab for one year. (AU)

Ferric Carboxymaltose Improves the Quality of Life of Patients with Inflammatory Bowel Disease and Iron Deficiency without Anaemia.

Background: Iron deficiency (ID) without anaemia is a common comorbidity associated with inflammatory bowel disease (IBD) that has a negative impact on health-related quality of life (HRQoL). Methods: This multicentre, prospective, observational study examined the response to, safety of and impact on HRQoL of a single 500 mg dose of intravenous ferric carboxymaltose (FCM) in patients with IBD and ID without anaemia. The diagnostic criteria for ID were low serum ferritin (<30 µg/L in the absence of inflammatory activity or <100 µg/L with inflammation) and transferrin saturation index (TSAT) < 16%. The effect on iron levels and HRQoL, according to the health status questionnaires SF-12v2 and EQ-5D, was evaluated 1 month after FCM infusion in an outpatient setting. Results: Of the 105 patients who received FCM, 98 patients completed the study. After 1 month, a single dose of FCM significantly increased serum ferritin, serum iron and TSAT. Importantly, patients reported fewer ID symptoms and problems on all EQ-5D dimensions. They also had higher EQ-5D visual analogue scale and SF-12v2 scores after treatment. FCM had similar clinical effects on men and women and on patients with Crohn's disease (n = 66) and ulcerative colitis (n = 32). Conclusion: A single dose of FCM rapidly restored iron parameters and significantly improved patients' symptoms and HRQoL at 1 month after treatment.

Impact of BMGIM Music Therapy on Emotional State in Patients with Inflammatory Bowel Disease: A Randomized Controlled Trial.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high prevalence of emotional disturbances which worsen the symptoms of the disease. As a therapeutic alternative that is part of a comprehensive care alongside medication, the Bonny Method of Guided Imagery and Music (BMGIM) music-assisted therapy has achieved promising emotional improvements in patients with chronic diseases. The objective of the study was to determine the impact of a treatment based on a BMGIM group adaptation on patients with inflammatory bowel disease (IBD) and their emotional state, therefore analyzing state of mind, quality of life, anxiety, depression, immunocompetence as a marker of well-being, and levels of acute and chronic stress. METHODS: Longitudinal, prospective, quantitative, and experimental study including 43 patients with IBD divided into an intervention group (22 patients), who received eight sessions over eight weeks, and a control group (21 patients). A saliva sample was taken from each patient before and after each session in order to determine cortisol and IgA levels. Similarly, a hair sample was taken before the first and after the last session to determine the cumulative cortisol level. All molecules were quantified using the ELISA immunoassay technique. In addition, patients completed several emotional state questionnaires: HADS, MOOD, and CCVEII. RESULTS: An improvement was observed in the following states of mind: sadness, fear, anger, and depression. No significant effect was observed in state of mind in terms of happiness or anxiety, in the levels of cortisol in hair, and in patients' perceived quality of life. A reduction in cortisol was observed in saliva, although this did not significantly affect the IgA titer. CONCLUSIONS: BMGIM seems to improve the emotional state of patients with IBD.

Real-world data on the infliximab biosimilar CT-P13 (Remsima®) in inflammatory bowel disease.

BACKGROUND: In recent years, biological therapies have revolutionized the management of inflammatory bowel disease (IBD); however, they are expensive. The development of biosimilar products has allowed us to reduce healthcare costs and improve patients' access to these treatments. Although various studies support the similarity between infliximab and its biosimilar CT-P13 in terms of efficacy and safety, there are unmet needs regarding research on these agents in the context of IBD. AIM: To analyze clinical response rates to CT-P13 and adverse events in IBD patients treated in real-life practice. METHODS: An observational, prospective, multicenter study of IBD patients treated with CT-P13 in clinical practice who were naïve to biological treatments or failed to respond to other anti-tumor necrosis factor drugs or had switched from infliximab originator was carried out. No diagnostic or follow-up interventions were conducted on patients outside usual clinical practice. The primary endpoints were clinical response rates and number of adverse events. The primary efficacy variable was the proportion of patients who were in clinical remission and/or had a clinical response at 3, 6, 9, and 12 mo. RESULTS: A total of 220 IBD patients treated with CT-P13 (Remsima®) were included in the study: 87 (40%) with ulcerative colitis and 133 (60%) with Crohn's disease. Mean age of the patients was 41.47 (SD 15.74) years, and 58% were female. Nineteen (9%) patients started treatment with CT-P13 after switching from infliximab. Of the remaining 201 patients, 142 (65%) were naïve to biologic agents. At baseline, 68.6% (n = 138/201) of patients presented with active disease. After 12 mo of treatment, 14.8% (n = 12/81) presented with active disease, and 64.2% (n = 52/81) were in clinical remission without corticosteroids. After 3 mo, 75.5% (n = 115/152) had a clinical response or achieved clinical remission, which was sustained for 12 mo (85.2%; n = 69/81). There was a decrease in specific IBD indices at 3, 6, 9, and 12 mo (P < 0.001). A total of 34 adverse events were reported by 27 (12.3%) patients, 9 (26.5%) of which were serious. CONCLUSION: CT-P13 is an effective and safe infliximab biosimilar for the treatment of IBD in real-life practice and may be a valid and attractive alternative for the treatment of IBD.

Successful use of golimumab in a patient with ulcerative colitis refractory to infliximab and adalimumab.

OBJECTIVE: To report a case of successful use of golimumab (GLB) in a patient with ulcerative colitis (UC) refractory to infliximab (IFX) and adalimumab (ADA). CASE SUMMARY: A 60-year-old man was diagnosed with left UC and was given azathioprine 2.5 mg/kg to control UC symptoms and decrease corticosteroid patient dependence. Four years later, he developed adverse reaction to azathioprine and began treatment with mercaptopurine 1.5 mg/kg/day. Despite this treatment, he developed a severe relapse (Truelove-Witts modified: 15 points). Treatment with IFX 5 mg/kg at weeks 0, 2, 6, and every 8 weeks was started. After 1 year in clinical remission, the patient developed an infusion reaction to IFX, and IFX was suspended. The patient started treatment with ADA 40 mg every other week. After 2 years in clinical remission, ADA was suspended. 20 months after ADA discontinuation, the patient developed an acute episode of UC with a Truelove-Witts modified score of 16 points. ADA plus corticosteroid therapy was restarted. Despite these treatments, the patient's clinical condition did not improved. ADA 40 mg per week was started with not clinical improvement and with corticosteroid dependence after 4 months of ADA intensive therapy. The patient denied surgery, and cyclosporine was discarded because of its inability to be used as a maintenance drug. The patient started GLB with an induction dosage regimen of 200 mg subcutaneous at week 0, followed by 100 mg at week 2, and then maintenance therapy with 100 mg every 4 weeks (patient's weight = 84 kg), combined with mercaptopurine and corticosteroids. After 6 weeks of treatment, the patient achieved clinical remission, with just three non-bleeding stools per day, without stomach ache, apyretic, and no urgency or tenesmus rectal symptoms. One year later, the patient continued to be asymptomatic with a Truelove-Witts modified score of 2 points, corticoid-free treatment, and a complete clinical and endoscopic remission and normal calprotectin levels (< 15 µg/g). We decided to suspend mercaptopurine in order to avoid side effects derived from the combined treatment. After 1 year on GLB therapy, the patient continued in clinical remission. CONCLUSIONS: Based on our case, GLB could be selected as an effective approach for patients with UC refractory to IFX and ADA. However, further studies need to be performed to evaluate the efficacy of GLB therapy as a rescue treatment.

The effect of a mindfulness-based therapy on different biomarkers among patients with inflammatory bowel disease: a randomised controlled trial.

Mindfulness-based interventions have shown some efficacy in decreasing stress levels and improving quality of life. However, so far, only a few studies have studied this type of intervention among patients with inflammatory bowel disease and none of them have studied their effects on inflammatory biomarkers. This current study was a two-armed, single-centre, randomised (2:1 ratio) controlled trial used to evaluate the effects of a mindfulness-based intervention (n = 37) compared to standard medical therapy (n = 20) in patients with Crohn's disease or ulcerative colitis. The mindfulness intervention blended four internet-based therapy modules with four face-to-face support sessions. The outcomes we assessed were faecal calprotectin (primary outcome), C-reactive protein, and cortisol levels measured in hair samples at several timepoints. The between-group analysis highlighted significant decreases in faecal calprotectin and in C-reactive protein levels in the mindfulness-based intervention group compared to the standard medical therapy group at the six-month follow-up (faecal calprotectin: -367, [95% CI: -705, -29], P = 0.03; C-reactive protein: -2.82, [95% CI: -5.70, 0.08], P = 0.05), with moderate to large effect sizes (faecal calprotectin: ηp2 = 0.085; C-reactive protein: ηp2 = 0.066). We concluded that mindfulness-based therapy administered as part of standard clinical practice effectively improves inflammatory biomarkers in patients diagnosed with inflammatory bowel disease.

Impact of comorbidities on anti-TNFα response and relapse in patients with inflammatory bowel disease: the VERNE study.

Objective: To evaluate the impact of comorbidities and extraintestinal manifestations of inflammatory bowel disease on the response of patients with inflammatory bowel disease to antitumour necrosis factor alpha (anti-TNFα) therapy. Design: Data from 310 patients (194 with Crohn's disease and 116 with ulcerative colitis) treated consecutively with the first anti-TNFα in 24 Spanish hospitals were retrospectively analysed. Univariate and multivariate logistic regression analyses were performed to assess the associations between inflammatory bowel disease comorbidities and extraintestinal manifestations with anti-TNFα treatment outcomes. Key clinical features, such as type of inflammatory bowel disease and concomitant treatments, were included as fixed factors in the model. Results: Multivariate logistic regression analyses (OR, 95% CI) showed that chronic obstructive pulmonary disease (2.67, 1.33 to 5.35) and hepato-pancreato-biliary diseases (1.87, 1.48 to 2.36) were significantly associated with primary non-response to anti-TNFα, as was the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn's disease). It was also found that myocardial infarction (3.30, 1.48 to 7.35) and skin disease (2.73, 1.42 to 5.25) were significantly associated with loss of response, along with the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn's disease). Conclusions: Our results suggest that the presence of some comorbidities in patients with inflammatory bowel disease, such as chronic obstructive pulmonary disease and myocardial infarction, and of certain extraintestinal manifestations of inflammatory bowel disease, such as hepato-pancreato-biliary conditions and skin diseases, appear to be related to failure to anti-TNFα treatment. Therefore, their presence should be considered when choosing a treatment. Trial registration number: NCT02861118.

The experience of inflammatory bowel disease patients with healthcare: A survey with the IEXPAC instrument.

To assess inflammatory bowel disease (IBD) patients' experience of chronic illness care and the relationship with demographic and healthcare-related characteristics.This cross-sectional survey used the Instrument to Evaluate the EXperience of PAtients with Chronic diseases (IEXPAC) questionnaire to identify parameters associated with a better healthcare experience for IBD patients. IEXPAC questionnaire responses are grouped into 3 factors - productive interactions, new relational model, and patient self-management, scoring from 0 (worst) to 10 (best experience). Scores were analyzed by bivariate comparisons and multiple linear regression models.Surveys were returned by 341 of 575 patients (59.3%, mean age 46.8 (12.9) years, 48.2% women). Mean (SD) IEXPAC score was 5.9 (2.0); scores were higher for the productive interactions (7.7) and patient self-management factors (6.7) and much lower for the new relational model factor (2.2). Follow-up by a nurse, being seen by the same physician, and being treated with a lower number of medicines were associated with higher (better) overall patient experience score, and higher productive interactions and self-management factor scores. A higher productive interactions score was also associated with patients receiving medication subcutaneously or intravenously. Higher new relational model scores were associated with follow-up by a nurse, affiliation to a patients' association, receiving help from others for healthcare, a lower number of medicines and a higher educational level.In patients with IBD, a better overall patient experience was associated with follow-up by a nurse, being seen by the same physician, and being treated with a lower number of medicines.

Withdrawal of Azathioprine in Inflammatory Bowel Disease Patients Who Sustain Remission: New Risk Factors for Relapse.

BACKGROUND: The benefits of immunosuppressants for sustaining remission and preventing flares of IBD are well known. However, optimal timing for withdrawal has not been determined. AIMS: The objective of this study was to calculate the risk of relapse and predictors after withdrawal of azathioprine (AZA) monotherapy in patients who sustain deep remission. METHODS: This was a multicenter observational study of patients with IBD in remission whose immunosuppressant had been withdrawn. We recorded demographic variables, disease data, laboratory values, and the results of imaging tests performed at withdrawal and, in patients who relapsed, time to relapse and the efficacy of reintroducing the drug. RESULTS: Ninety-five patients were included (35 UC and 60 CD). The mean duration of AZA treatment was 87 and 77 months for UC and CD, respectively. Endoscopic remission was evaluated in 23 patients with UC and 35 with CD. After AZA withdrawal, 91% patients with UC and 67% with CD received high doses of salicylates. A total of 26 patients relapsed. The cumulative relapse rate at 5 years was 46% for CD and UC. AZA was reintroduced in 19 patients, of whom 14 responded. Predictors of relapse were corticosteroid dependence, early introduction of AZA (CD), and late introduction of AZA (UC). CONCLUSIONS: Almost half of the patients in whom AZA was withdrawn were in remission at 5 years. The candidates for withdrawal could be better identified based on corticosteroid dependence, previous surgery, timing of initiation, and indication for AZA.

Inflammatory bowel disease in patients over the age of 70 y. Does the disease duration influence its behavior?

INTRODUCTION: The fastest growing segment of our population is that of people above 70 years of age. Elderly patients with IBD exhibit several specific problems. Our objective was to evaluate the clinical course, the side effects of the treatments and the need for surgery of elderly patients, regardless of the age of onset. MATERIALS AND METHODS: This was a cross-sectional study wherein retrospective data were collected from multiple centers from seven hospitals within the Valencia metropolitan area. Data were collected on patients older than 70 y with inflammatory bowel disease. RESULTS: We identified a total of 331 patients older than 70 years of age (5.3% of patients monitored at our centers). The mean age at the time of the study was 77.34 y (±5.39). Mesalamine were the most frequently used medications. Corticosteroids were used in 66% of the patients. However, the use of corticosteroids and biologics was less probable in older patients (OR 0.96, p = .06). The longer the disease progressed, the more immunosuppressive medications were used (OR 1.3, p = .052). Neoplasms appeared in 41 patients (13%). Of the 36 patients with tumors that appeared after the onset of the disease, 20 patients had not been treated with immunomodulators or biologics. CONCLUSIONS: Mesalamine was the most frequently used medication. There is no increased risk of tumors regarding the medications used. The use of immunosuppressive medications is more prevalent with longer disease progression times, although with a high rate of adverse events.

Legionella pneumophila pneumonia possibly due to ustekinumab therapy in a patient with Crohn's disease.

PURPOSE: A case report of Legionella pneumophila pneumonia associated with off-label use of ustekinumab in a patient with Crohn's disease (CD) is presented. SUMMARY: A 57-year-old man with longstanding CD was hospitalized with a four-day history of fever (38.5 °C), dyspnea, left pleuritic pain, and weight loss (more than 6 kg) about six weeks after beginning treatment with ustekinumab, a human monoclonal antibody approved in the United States for two indications (plaque psoriasis and psoriatic arthritis) and currently under investigation as a potential treatment for CD and other inflammatory disorders. During the preceding 25 years, the man had been treated for severe CD with a number of agents (e.g., infliximab, adalimumab, certolizumab); ultimately, off-label ustekinumab therapy (90 mg subcutaneously weekly) was initiated due to persistent severe CD symptoms. Chest x-ray studies at the time of admission demonstrated left upper lobar consolidation, and a urine antigen test was positive for L. pneumophila. The patient was treated with i.v. levofloxacin and methylprednisolone and discharged after two weeks. Ustekinumab was reintroduced (45 mg subcutaneously every two weeks), and the patient continued to receive the drug for 16 months, with clinical remission of CD symptoms and no further adverse events. A literature search identified two case reports of pneumonia associated with ustekinumab use, but neither case involved L. pneumophila. CONCLUSION: Pneumonia caused by L. pneumophila developed in a patient with CD treated with ustekinumab. Pneumonia symptoms resolved after ustekinumab was discontinued.

Effectiveness of a systematic vaccination program in patients with autoimmune inflammatory disease treated with anti-TNF alpha drugs.

OBJECTIVE: The objective of this is manuscript is to evaluate the impact of a vaccination protocol in the prevention of infection in autoimmune inflammatory disease (AUTID) patients treated with Anti-TNF-alpha therapies. RESEARCH DESIGN AND METHODS: The authors conducted an observational study to test the effect of a vaccination program in AUTID patients that received anti-TNF-alpha therapies in hospital admissions related to infections. This effect was evaluated by comparing patients admitted before the program started (prevaccination period, 2009-2011) and after the program (postvaccination period, 2011-2014). RESULTS: The study included 581 patients: 280 in the pre-vaccination group and 301 in the post-vaccination group. During the prevaccination period, 27.3% of patients treated with anti-TNF-alpha drugs were vaccinated before biological therapy. During the postvaccination period, this percentage increased to 97.0%. Statistically significant differences were detected in emergency room visits per 10.000 treatment days, in hospital admissions related to an infectious disease and in the rate of invasive pneumococcal disease due to Streptococcus pneumoniae infection per 10.000 days of treatment. CONCLUSIONS: This vaccination program decreases infectious complications and was associated with a lower amount of hospital admissions due to infections, emergency room visits and the rate of invasive pneumococcal disease.

Diagnostic Performance of the Simple Clinical Colitis Activity Index Self-Administered Online at Home by Patients With Ulcerative Colitis: CRONICA-UC Study.

OBJECTIVES: New e-health technologies can improve patient-physician communication and contribute to optimal patient care. We compared the diagnostic performance of the Simple Clinical Colitis Activity Index (SCCAI) self-administered by patients with ulcerative colitis (UC) at home (through a website) with the in-clinic gastroenterologist-assessed SCCAI. METHODS: Patients were followed-up over 6 months. At months 3 and 6, patients completed the SCCAI online at home; within 48 h, gastroenterologists (blinded to patients' scores) completed the in-clinic SCCAI (reference). SCCAI scores were dichotomized to remission or active disease, and SCCAI changes in disease activity from month 3 to 6 were classed as worsening, stability, or improvement. RESULTS: A total of 199 patients (median age: 38 years; 56% female) contributed with 340 pairs of questionnaires. Correlation of SCCAI scores by patients and physicians was good (Spearman's ρ=0.79), with 85% agreement for remission or activity (95% CI: 80.8-88.6, κ=0.66). The negative predictive value for active disease was 94.5% (91.4-96.6); the positive predictive value was 68.0% (58.8-69.2). Agreement between patient and physician was higher in the 168 month 6 pairs than in the 172 month 3 pairs of questionnaires (89.3% (83.6-93.1) vs. 80.8% (74.2-86.0), P=0.027). CONCLUSIONS: In patients with UC, SCCAI self-administration via an online tool resulted in a high percentage of agreement with evaluation by gastroenterologists, with a remarkably high negative predictive value for disease activity. Remote monitoring of UC patients is possible and might reduce hospital visits.

Successful use of infliximab and tacrolimus combination therapy in a patient with ulcerative colitis refractory to infliximab dose intensification plus azathioprine.

OBJECTIVE: To report of a case successful use of infliximab (IFX) and tacrolimus (TAC) in a patient with ulcerative colitis (UC). CASE SUMMARY: A 22-year-old woman diagnosed with UC started treatment with azathioprine 2.5 mg/kg. After 3 years of therapy, she developed a severe relapse. A colonoscopy was performed showing diffuse continuous mucosal disease and multiple erosions (< 5 mm) with no signs of spontaneous bleeding. Treatment with IFX 5 mg/kg at weeks 0, 2, and 6 was started. After IFX induction, she remained with symptoms: six stools per day, as well as presenting bloody diarrhea, tenesmus, and no abdominal pain. An IFX dose intensification of 5 mg/kg every 6 weeks was prescribed. After 6 months of azathioprine plus IFX therapy, patient's clinical condition was improved: 3 - 4 stools per day, 20% of bloody diarrhea, tenesmus, and no abdominal pain. Her Mayo endoscopic subscore was 6.3 months later, and a severe relapse of ulcerative colitis was presented. The patient refused a surgical treatment. Azathioprine 2.5 mg/kg/day was suspended and TAC 0.2 mg/kg/day (12 mg/day) as a compassionate use was added to IFX dose intensification of 10 mg/kg every 8 weeks and mesalamine 800 mg 3 times daily. After the first month of combined therapy, the patient's clinical condition improved with no bloody stools and abdominal pain. After 6 months of combination therapy, the patient was in remission, with two stools per day, no tenesmus and no abdominal pain. Due to the patient's clinical remission, IFX was suspended. Tacrolimus was continued on 10 mg/day. After 6 months of TAC monotherapy, the patient continued without symptoms (1 - 2 normal stools per day). CONCLUSIONS: Based on our case, the combination therapy of IFX and TAC could be selected as an effective approach for the patients with UC refractory to IFX dose intensification plus AZA. However, further studies need to be performed to evaluate the efficacy of this combination therapy.

Short-term effectiveness of golimumab for ulcerative colitis: Observational multicenter study.

AIM: To evaluate the real-world effectiveness of golimumab in ulcerative colitis (UC) and to identify predictors of response. METHODS: We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at week 0 and 14 with the physician's global clinical assessment (PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS database. RESULTS: Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC (E2) and 70% had extensive UC (E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor (TNF) treatment naïve, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at week 14 (a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 µg/g, and 170.5 µg/g at week 14. Being anti-TNF treatment naïve was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of follow-up. Only three adverse effects (AEs) were observed during the study; all were mild and golimumab was not interrupted. CONCLUSION: This real-life practice study endorses golimumab's promising results, demonstrating its short-term effectiveness and confirming it as a safe drug during the induction phase.

Dealing with the high cost of biological therapies: developing and implementing a biological therapy prioritization protocol for ankylosing spondylitis patients in a tertiary hospital.

OBJECTIVE: In January 2011, a biological therapies commission was created in our hospital to fully address the management of biological drugs. A biological therapy prioritization protocol was developed for ankylosing spondylitis (AS) patients. Here, we describe it and report on its economic impact to illustrate how we are optimizing the use of these expensive new drugs. METHODS: The biological therapies commission established several procedures for the rational use of biological drugs such as cost-efficiency therapeutic protocols, pharmacovigilance, and therapeutic drug monitoring programs. The AS protocol was based on clinical and economic aspects. We estimated the economic impact of the protocol by comparing the cost of treating AS patients with biological drugs in the pre-commission (2009 - 2010) vs. post-commission period (2011 - 2013). AS patients treated with adalimumab (ADA), etanercept (ETN) or infliximab (IFX) for at least 6 months in the 2009 - 2013 period were included. RESULTS: 107 patients were included. In the pre-commission period, total expenses increased by +30,944 Euro (+4%). After protocol implementation, total expenses decreased by 11,441 Euro (-1%) during 2011, and by an additional 36,781 Euro (-4%) and 53,872 Euro (-8%) in 2012 and 2013, respectively. In the 2010 - 2013 period the cost of biological therapy per patient-year decreased by 869 €, suggesting the positive effects of the biological therapy prioritization protocol instauration. CONCLUSION: We describe the establishment of a multidisciplinary biological therapy commission to optimize the use of biological therapies. We illustrate its work in developing a protocol for the management of AS patients with such therapies. We show that after 3-years of implementation, the biological therapy prioritization protocol allowed us to steadily decrease the direct cost of biological drug therapies per patient, up to 869 Euro.

Successful use of infliximab and tacrolimus in a patient with Crohn's disease.

OBJECTIVE: To report a case of successful use of infliximab (IFX) and tacrolimus (TAC) in a patient with Crohn's disease (CD). CASE SUMMARY: A 42-year-old man with no significant previous medical history was referred to our emergency department because of a 3-month history of weight loss, severe abdominal pain, and bloody diarrhea. His Harvey Bradshaw Index was 39. Ileocolonoscopic revealed severe Crohn colitis. Treatment with IFX 5 mg/kg, azathioprine 2.5 mg/kg/day and corticosteroids was started. After a second IFX infusion, he remained with symptoms with a Harvey Bradshaw Index of 17. An IFX dose intensification of 10 mg/kg every 8 weeks was prescribed. After 16 weeks, a new colonoscopic examination revealed multiple deep ulcerations in sigma and rectum. IFX was intensified to 10 mg/kg every 6 weeks. After 4 doses of IFX intensified dose, the patient's clinical condition was not improved, with a Harvey Bradshaw Index of 10. Azathioprine (AZA) 2.5 mg/kg/day was suspended. Tacrolimus 0.2 mg/kg/day as a compassionate use was added to IFX 10 mg/kg every 6 weeks. After 6 months of combination therapy, the patient was in clinical remission. His Harvey Bradshaw Index was 3. After 1 year on combination IFX and TAC therapy, the patient continued in clinical remission. CONCLUSIONS: This case documents that the combination therapy of IFX and TAC could be selected as an effective approach for patients with CD refractory to IFX dose-intensification plus AZA. However, further studies need to be performed to evaluate the efficacy of this combination therapy.

Safety of ferric carboxymaltose immediately after infliximab administration, in a single session, in inflammatory bowel disease patients with iron deficiency: a pilot study.

AIM: To obtain preliminary safety and efficacy data on intravenous (IV) administration of infliximab (IFX) and ferric carboxymaltose (FCM) to inflammatory bowel disease (IBD) patients in a single treatment session. METHODS: A two-phase non-interventional, observational, prospective pilot study was performed to evaluate safety and efficacy of FCM given immediately after IFX. IBD patients were recruited consecutively in the outpatient clinic in two groups. Control group patients (n = 12) received FCM on a separate day from IFX. Subsequently, single-session group patients (n = 33) received FCM after IFX on the same day. All patients received 5mg/kg IFX and 1000mg FCM for iron-restricted anemia (IRA) or 500mg FCM for iron deficiency without anemia. Safety assessment was performed by recording adverse events (AEs) during and immediately after infusion, 30 minutes afterwards, and via follow-up at 7 days and 8 weeks. For efficacy assessment, hematological parameters were assessed prior to FCM infusion (pre-FCM) and after 8 weeks. Economic impact of FCM given immediately after IFX was assessed. RESULTS: All 45 patients (35 Crohn´s disease, 10 ulcerative colitis) received IFX 5mg/kg. 21 patients received 500mg FCM and 24 received 1000mg. FCM administration immediately after IFX corrected iron deficiency or IRA as shown by increases in hematological parameters. No AEs were reported during the safety evaluation at the end of FCM or IFX administration, 30 minutes, 7 days and 8 weeks afterwards, in either control or single-session groups. Total cost per patient for single-session administration was 354.63€; for patients receiving IFX and FCM on separate days, it was 531.94€, giving a 177.31€ per-patient cost saving. CONCLUSION: Single-session administration of FCM after IFX was safe and effective in IBD patients and can offer a good cost-benefit ratio and improve treatment adherence. To our knowledge, this study is the first to evaluate FCM and IFX administration in a single treatment session.