Early dose optimization of golimumab induces late response and long-term clinical benefit in moderately to severely active ulcerative colitis.

Aim: To evaluate outcomes of early dose optimization of golimumab in ulcerative colitis (UC) patients with inadequate response to golimumab induction treatment. Methods: This observational, multicenter, cohort study included patients with moderate-to-severe active UC and with inadequate response to subcutaneous golimumab induction doses, in whom weight-based golimumab maintenance dose (European labeling) of 50 mg every 4 weeks (q4wk) was optimized before week 14 to 100 mg q4wk. At week 14, we assessed clinical response and remission using the partial Mayo score. In the long term we evaluate the cumulative probabilities of golimumab failure-free survival and colectomy-free survival. Results: A total of 209 patients who received golimumab induction doses were eligible. Of these, 151 patients (72.2%) weighing less than 80 kg were assigned to a golimumab maintenance dose of 50 mg q4wk. Twenty-four patients (15.9% [12.5% overall]), in whom scheduled doses of 50 mg q4wk were optimized to 100 mg q4wk before week 14, compose the study population. At week 14, 16 patients (66.7%, 95% CI 45.7-87.6) had clinical response, of these 12 were corticosteroid free. Four patients (16.7%) achieved corticosteroid-free remission. After a median follow-up of 12 months (IQR 10-22), 13 patients (54.2%) maintained clinical benefit. Thirteen of 16 patients (81.2%) with clinical response at week 14 maintained clinical benefit at last follow-up. All patients avoided colectomy. In none of the patients was golimumab dose de-escalated. There were no adverse events leading to golimumab withdrawal. Conclusion: Early optimization of golimumab dose induces clinical response at week 14 in two thirds of UC patients and leads to long-term clinical benefit in over half of patients.

Enfermedades inflamatorias mediadas por inmunidad en pacientes con enfermedad inflamatoria intestinal. Datos basales del estudio Aquiles / Immune-mediated inflammatory diseases in patients with inflammatory bowel disease. Baseline data from the Aquiles study

OBJETIVO: Determinar la prevalencia de enfermedades inflamatorias mediadas por inmunidad (EIMI) en una cohorte de pacientes con enfermedad inflamatoria intestinal (EII) reclutada en consultas hospitalarias de aparato digestivo para el estudio Aquiles, un estudio prospectivo de 2 años de seguimiento. Material y métodos Se incluyeron pacientes de ≥ 18 años con diagnóstico previo o nuevo de EII (enfermedad de Crohn [EC], colitis ulcerosa [CU] o colitis indeterminada). Los diagnósticos se recogieron de forma transversal de la historia clínica en el momento de incorporar a cada paciente al estudio. Resultados Se incluyeron 526 pacientes (edad media 40,2 años; 47,3% hombres, 52,7% mujeres), 300 con EC (57,0%), 218 con CU (41,4%) y 8 colitis indeterminada. Presentaron otra EIMI 71 pacientes (prevalencia: 13,5%, IC 95%: 10,8-16,7): 47 fueron espondiloartritis (prevalencia: 8,9%); 18 psoriasis (3,4%); 5 pioderma gangrenoso (1,0%) y 11 uveítis (2,1%). La prevalencia de EIMI fue mayor en pacientes con EC respecto a pacientes con CU (17,0% [IC 95%: 13,2-21,7] frente a 9,2% [IC 95%: 6,0-13,8], p = 0,011). En el análisis multivariante, las variables asociadas a la presencia de EIMI fueron el diagnóstico de EC (OR = 1,8 [IC 95%: 1,1-3,2]) y un tiempo de evolución de la EII ≥ 4 años (OR = 2,1 [IC 95%: 1,1-4,1] en aquellos con 4-8 años, y OR = 2,1 [IC 95%: 1,2-3,9] en los de ≥ 8 años frente a < 4 años). CONCLUSIONES: En la cohorte de pacientes con EII del estudio Aquiles, el 13,5% presentó otra EIMI, con una prevalencia mayor en pacientes con EC y > 4 años de evolución de la enfermedad

OBJECTIVE: To determine the prevalence of immune-mediated inflammatory diseases (IMID) in a cohort of patients with inflammatory bowel disease(IBD) enrolled in hospital gastroenterology outpatients units for the AQUILES study, a prospective 2-year follow-up study. MATERIAL AND METHODS: We included patients ≥18 years old with a prior or new diagnosis of IBD (Crohn disease [CD], ulcerative colitis [UC] or indeterminate colitis). Diagnoses were collected in a cross-sectional manner from the clinical records at enrollment of a new patient in the study. RESULTS: We included 526 patients (mean age 40.2 years; 47.3% men, 52.7% women), 300 with CD (57.0%), 218 with UC (41.4%) and 8 with indeterminate colitis. Other types of IMID were present in 71 patients (prevalence: 13.5%, 95% CI: 10.8-16.7): 47 were spondyloarthropathies (prevalence: 8.9%); 18 psoriasis (3.4%); 5 pyoderma gangrenosum (1.0%), and 11 uveitis (2.1%). The prevalence of IMID was higher in patients with CD than in those with UC (17.0% [95% CI: 13.2-21.7] vs 9.2% [95% CI: 6.0-13.8], p=0.011). In the multivariate analysis, the variables associated with the presence of IMID were diagnosis of CD (OR=1.8 [95% CI: 1.1-3.2]) and duration of IBD ≥4 years (OR=2.1 [95% CI: 1.1-4.1] in those with disease duration 4-8 years, and OR=2.1 [95% CI: 1.2-3.9] in those with ≥8 years vs. <4 years).CONCLUSIONS: In the cohort of patients with IBD in the AQUILES study, 13.5% had another IMID, with a higher prevalence in patients with CD and>4 years since disease onset (AU)

[Immune-mediated inflammatory diseases in patients with inflammatory bowel disease. Baseline data from the Aquiles study]. / Enfermedades inflamatorias mediadas por inmunidad en pacientes con enfermedad inflamatoria intestinal. Datos basales del estudio Aquiles.

OBJECTIVE: To determine the prevalence of immune-mediated inflammatory diseases (IMID) in a cohort of patients with inflammatory bowel disease (IBD) enrolled in hospital gastroenterology outpatients units for the AQUILES study, a prospective 2-year follow-up study. MATERIAL AND METHODS: We included patients ≥18 years old with a prior or new diagnosis of IBD (Crohn disease [CD], ulcerative colitis [UC] or indeterminate colitis). Diagnoses were collected in a cross-sectional manner from the clinical records at enrollment of a new patient in the study. RESULTS: We included 526 patients (mean age 40.2 years; 47.3% men, 52.7% women), 300 with CD (57.0%), 218 with UC (41.4%) and 8 with indeterminate colitis. Other types of IMID were present in 71 patients (prevalence: 13.5%, 95% CI: 10.8-16.7): 47 were spondyloarthropathies (prevalence: 8.9%); 18 psoriasis (3.4%); 5 pyoderma gangrenosum (1.0%), and 11 uveitis (2.1%). The prevalence of IMID was higher in patients with CD than in those with UC (17.0% [95% CI: 13.2-21.7] vs 9.2% [95% CI: 6.0-13.8], p=0.011). In the multivariate analysis, the variables associated with the presence of IMID were diagnosis of CD (OR=1.8 [95% CI: 1.1-3.2]) and duration of IBD ≥4 years (OR=2.1 [95% CI: 1.1-4.1] in those with disease duration 4-8 years, and OR=2.1 [95% CI: 1.2-3.9] in those with ≥8 years vs. <4 years). CONCLUSIONS: In the cohort of patients with IBD in the AQUILES study, 13.5% had another IMID, with a higher prevalence in patients with CD and>4 years since disease onset.

Open-label infliximab therapy in Crohn’s disease: a long-term multicenter study of efficacy, safety and predictors of response

OBJETIVO: La eficacia de infliximab en la enfermedad deCrohn (EC), demostrada por los diferentes ensayos clínicos,ha de ser confirmada en la práctica clínica. Nuestro objetivofue evaluar la eficacia y la seguridad del infliximab en pacientescon EC del área de Madrid, buscando predictores derespuesta.MÉTODOS: Estudio retrospectivo y multicéntrico que incluyelos pacientes con EC tratados con infliximab en 8 hospitalesde la Comunidad de Madrid, con un seguimiento mínimo de14 semanas.RESULTADOS: Se incluyó a un total de 169 pacientes (un 48%varones, con una edad de 39 ± 12 años), un 64% con enfermedadperianal y un 82% bajo tratamiento inmunosupresor.Se administraron un total de 1.355 perfusiones de infliximab(media, 8; rango, 1-30): un 90% de los pacientesrespondió, un 48% alcanzó la remisión clínica, un 73% siguiótratamiento de mantenimiento, y un 78% mantuvo omejoró su respuesta tras un seguimiento medio de 28 meses(rango, 3,5-86). Se perdió la respuesta durante el seguimientode 24 pacientes, tras una media de 41 semanas (rango, 6-248). Sólo la prescripción de tratamiento de mantenimientofue un predictor favorable de respuesta (p < 0,01); se contabilizaron 17 reacciones infusionales (en el 10% de los pacientes,el 1,2% de las perfusiones; sólo se constató un casograve) y fueron causa de la suspensión del tratamiento en 7pacientes. El cotratamiento con los inmunosupresores y eltratamiento de mantenimiento con infliximab fueron los factoresprotectores para sufrir reacciones infusionales (p <0,05). Otros efectos adversos se produjeron en el 26% de lospacientes, y fueron causa de suspensión del tratamiento en 7pacientes.CONCLUSIONES: Infliximab es eficaz y seguro en el tratamientode la EC, pero deberían prescribirse el tratamientode mantenimiento y el concomitante con inmunosupresorespara obtener los mejores resultados. Esto confirma en un escenariode práctica clínica real los resultados obtenidos enensayos clínicos

BACKGROUND: Efficacy of infliximab in Crohn’s disease(CD) showed by randomized controlled trials must beconfirmed in clinical practice. We aimed to evaluate efficacyand safety of infliximab in CD patients of the Madrid area,looking for clinical predictors of response.METHODS: Multicenter retrospective survey of all CD patientstreated with infliximab in 8 University hospitals of theMadrid area (Spain) with a minimum follow up of 14wks.RESULTS: 169 patients included (48%males, mean age 39 ±12 yrs). 64% of them had perianal disease. 82% were underimmunosuppressants. 1355 infliximab infusions administered(mean 8, range 1-30). 90% response rate and 48%remission rate were obtained with induction therapy. 73%followed maintenance treatment, and 78% of them maintainedor improved the response after a mean follow up of 28months (range 3.5-86). 24 patients lost response during thefollow up, after a mean of 41wks (range 6-248). Only theprescription of maintenance therapy was predictive factorfor favourable response (p < 0.01). 17 infusion reactionswere reported (10% of the patients, 1.2% of the infusions;only one case was severe) and were the cause of treatmentwithdrawal in 7 patients. Co-treatment with immunosuppressivedrugs and maintenance infliximab therapy wereprotective factors for infusion reactions (p < 0.05). Other adverseevents occurred in 26% of the patients, and were causeof treatment withdrawal in 7 patients.CONCLUSIONS: Infliximab is effective and safe for CD managementbut concomitant immunosuppressive drugs andmaintenance treatment should be prescribed to obtain thebest outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials (AU)