Daniel Ceballos

Usefulness of oral beclometasone dipropionate in the treatment of active ulcerative colitis in clinical practice: The RECLICU Study

BACKGROUND Beclometasone dipropionate (BDP) is a relatively new topically acting oral steroid to treat mild to moderately active ulcerative colitis (UC). We estimate that 20,000 patients have received oral BDP in Spain in the last two years. Our aim was to evaluate the efficacy and safety of oral BDP in clinical practice. METHODS Retrospective and multicenter study that included 434 patients with active UC treated with BDP. The partial Mayo Clinic score (pMS, 0-9) was used to measure disease activity. Remission was defined as post-treatment pMS of 0 or 1; response as a decrease in pMS of 3 points or 2 points and >30%, and failure as lack of remission or response. RESULTS BDP dose was 5 mg/day in 88% of patients and mean treatment duration was 6.2 weeks. BDP achieved remission in 44.4%, response in 22.3% and failed in 33.2% of patients. Mean pMS decreased from 4.9 ± 1.3 to 2.4 ± 2.3 (p<0.0001). Remission rate was higher in mild and moderate than in severe UC (p<0.043) and tended to be higher in left-sided and extensive UC than in proctitis (p<0.06). Failure was less frequent in patients treated for >4 weeks (p<0.02). Mild adverse events were reported in 7.6% of patients. CONCLUSION BDP induces response or remission in two thirds of active UC patients, with a good safety profile. Patients with mild to moderate, left-sided or extensive UC, receiving BDP for more than 4 weeks are most likely to benefit from this treatment.

Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn’s Disease Recurrence. A GETECCU Randomised Trial

Background and Aims Postoperative recurrence of Crohns disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting. Methods We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader. Results We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions. Conclusions ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. ClinicalTrials.gov NCT01564823.

Resources Utilization and Costs the Year Before and After Starting Treatment with Adalimumab in Crohnʼs Disease Patients

Background:This study examines the resources utilization in patients with Crohns disease (CD) during the year before (Y − 1) and after (Y + 1) starting treatment with adalimumab and the drugs efficiency. Methods:Observational, multicenter, prospective cohort study of patients with CD naive to biological drugs. The proportion of patients with CD Activity Index (CDAI) <150 was considered as the effectiveness variable. Costs considered were direct costs (DC) related to the use of health care resources, and indirect costs (IC) related to sick leave in Y − 1 and Y + 1. Adalimumab efficiency was estimated as the incremental cost/effectiveness ratio. A deterministic sensitivity analysis was performed building 3 scenarios: base case, the least favorable, and the most favorable case for adalimumab. Results:In the cohort of 126 patients (50.8% men; age 39.1 ± 13.8 yr), the proportion of patients in remission increased from 34.1% by the end of Y − 1 to 83.3% by the end of Y + 1. Although the DC increase by the use of adalimumab, the use of doctor visits, emergency room visits, laboratory tests, diagnostic examinations, and nonbiological drug treatment were lower (P < 0.05) in Y + 1 than Y − 1. In the base case scenario, considering only DC, the incremental cost/effectiveness ratio was &OV0556;31,308 and including IC, it was &OV0556;28,936. In patients with CDAI > 150 at the onset, incremental cost/effectiveness ratio was &OV0556;20,119 and &OV0556;18,223, considering DC alone or included IC, respectively. Conclusions:In patients with CD, adalimumab increases pharmacological costs at the expense of biological therapy but reduces the cost of other drugs, the use of health care resources, and IC. Adalimumab efficiency is 30% greater in patients with CDAI > 150.

Serial Tuberculin Skin Tests Improve the Detection of Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease

Aim To assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST. Methods In this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up. Results Of the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years]. Conclusions Serial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.

Early Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease

Background and Aim Sensitivity of tuberculin skin test [TST] during screening for latent tuberculosis infection [LTBI] is affected by steroid and/or immunosuppressant therapy. The aim of this study was to compare performance of the two-step TST in inflammatory bowel disease patients immediately before anti-tumour necrosis factor [TNF] therapy as part of routine screening for LTBI vs control patients when the TST was carried out at an early stage. Methods In this multicentre prospective controlled study, we evaluated the performance of two-step TST with 5-mm threshold. Factors associated with TST results were determined by logistic regression. Results We evaluated 243 candidates for anti-TNF therapy and 337 control patients. Overall, 105 patients [18.1%] had an induration ≥ 5 mm in the first TST or in TST retest. LTBI was diagnosed in 25% of patients by TST retest. Twenty-eight [11.5%] anti-TNF group patients vs 77 [22.8%] control patients had a positive TST (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.28-0.70; P < 0.001]. In multivariate analysis, positive TST was associated with higher age [OR 2.63, 95% CI 1.21-5.72; P < 0.001] and 5-aminosalicylate therapy [OR 1.86, 95% CI 1.14-3.05; P = 0.013]. Negative TST was associated with steroid therapy [OR 0.36, 95% CI 0.16-0.83; P = 0.016], immunosuppressant therapy [OR 0.36, 95% CI 0.21-0.62; P < 0.001], or steroids + immunosuppressant therapy [OR 0.20, 95% CI 0.07-0.59; P = 0.004]. Conclusions The sensitivity of routine TST performed just before starting anti-TNF therapy is low. TST performed at an early stage enables screening in the absence of immunosuppressive treatment and thus maximises the diagnostic yield of TST for detecting LTBI.

P257 Surgical and hospital admission in adults newly diagnosed with inflammatory bowel disease (IBD) in the biological era in Spain: Results of the nationwide EpidemIBD study of GETECCU

M. Chaparro1,2,3,4*, J.L. Cabriada5, M.J. Casanova1,2,4, D. Ceballos6, M. Esteve4,7, H. Fernández8, M. Barreiro-de Acosta9, V. GarcíaSánchez10,11, D. Ginard12, F. Gomollón4,13,14, R. Llorente Poyatos15, P. Nos4,16, S. Riestra17, M. Rivero18, P. Robledo19, C. Rodríguez Gutiérrez20, B. Sicilia21, E. Torrella22, E. García Esquinas23,24,25, J.P. Gisbert1,2,3,4, on behalf of the EpidemIBD group 1Hospital Universitario de La Princesa, Gastroenterology Unit, Madrid, Spain, 2Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain, 3Universidad Autónoma de Madrid, Madrid, Spain, 4Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain, 5Hospital de Galdakao-Usansolo, Gastroenterology Unit, Vizcaya, Spain, 6Hospital Universitario de Gran Canaria Doctor Negrín, Gastroenterology Unit, Las Palmas de Gran Canaria, Spain, 7Consorci Sanitari Terrassa, Gastroenterology Unit, Tarrasa, Spain, 8Hospital San Pedro, Gastroenterology Unit, Logroño, Spain, 9Hospital Clínico Universitario de Santiago, Gastroenterology Unit, Santiago de Compostela, Spain, 10Hospital Universitario Reina Sofía, Gastroenterology Unit, Córdoba, Spain, 11IMIBIC, Córdoba, Spain, 12Hospital Universitario Son Espases, Gastroenterology Unit, Palma de Mallorca, Spain, 13Hospital Clínico Universitario Lozano Blesa, Gastroenterology Unit, Zaragoza, Spain, 14ISS Aragón, Zaragoza, Spain, 15Hospital General Universitario de Ciudad Real, Gastroenterology Unit, Ciudad Real, Spain, 16Hospital Universitario y Politécnico de La Fe, Gastroenterology Unit, Valencia, Spain, 17Hospital Universitario Central de Asturias, Gastroenterology Unit, Oviedo, Spain, 18Hospital Universitario de Marqués de Valdecilla, Gastroenterology Unit, Santander, Spain, 19Hospital San Pedro de Alcántara, Gastroenterology Unit, Cáceres, Spain, 20Complejo Hospitalario de Navarra, Gastroenterology Unit, Pamplona, Spain, 21Hospital Universitario de Burgos, Gastroenterology Unit, Burgos, Spain, 22Hospital General Universitario Morales Meseguer, Gastroenterology Unit, Murcia, Spain, 23Universidad Autónoma de Madrid, Preventive Medicine and Public Health, Madrid, Spain, 24IdiPAZ, Madrid, Spain, 25Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

Clinical status, quality of life, and work productivity in Crohn’s disease patients after one year of treatment with adalimumab

OBJECTIVE Clinical trials have shown the efficacy of adalimumab in Crohns disease, but the outcome in regular practice remains unknown. The aim of the study was to examine clinical status, quality of life, and work productivity of Crohns disease patients receiving adalimumab for one year in the context of usual clinical practice. MATERIAL AND METHODS This was a prospective, observational study with a one-year follow-up. After baseline, Crohns disease patients were evaluated at 1, 3, 6, 9, and 12 months after starting treatment with adalimumab. Outcome variables included: clinical status (measured with CDAI), quality of life (measured with EuroQoL-5D and IBDQ), and work productivity (measured with WPAI questionnaire). These outcome variables were compared using the Students t test or Wilcoxon test for paired comparison data according to the data distribution. Statistical significance was set at two-sided p < 0.05. RESULTS The sample was composed of 126 patients (age [mean] 39.1 ± [standard deviation] 13.8 years; 51% male). Significant changes were observed during the follow-up period: CDAI decreased from [median] 194 ([25-75 percentiles] 121-269) to 48.2 (10.1-122.0) (p < 0.05); the EuroQoL-5D increased from 0.735 (0.633-0.790) to 0.797 (0.726-1.000) (p < 0.05); the EuroQoL-5D visual analogue scale increased from 50.0 (40-70) to 80.0 (60-90); (p < 0.05) and the IBDQ increased from 56.7 (51.6-61.5) to 67.5 (60.1-73.6) (p < 0.05). The total work productivity impact decreased from 53% to 24% (p < 0.05). CONCLUSIONS In regular practice, adalimumab is clinically effective in the treatment of Crohns disease patients and results in a significant improvement in quality of life and work productivity.