ABSTRACT
Intestinal dysbiosis is key in the onset and development of Crohn's disease (CD). We evaluated the microbiota changes in CD patients before and after a six-month anti-TNF treatment, comparing these changes with the microbiota of healthy subjects. This prospective multicenter observational study involved 27 CD patients initiating anti-TNF treatment and 16 healthy individuals. Inflammatory activity was determined at baseline, 3 and 6 months, classifying patients into responders and non-responders. Fecal microbiota was analyzed by massive genomic sequencing thought 16S rRNA amplicon sequencing before and after six months of anti-TNF treatment. The CD cohort showed a decrease in genera of the class Clostridia, short-chain fatty acid producers, and an increase in the phylum Proteobacteria (p < 0.01) versus the healthy cohort. After anti-TNF treatment, the phylum Proteobacteria also increased in non-responders versus responders (13/27) (p < 0.005), with the class Clostridia increasing. In addition, alpha diversity increased in responders versus non-responders (p < 0.01), tending towards eubiosis. An association was found (p < 0.001) in the F.prausnitzii/E.coli ratio between responders and non-responders. The F/E ratio was the most accurate biomarker of anti-TNF response (area under the curve 0.87). Thus, anti-TNF treatment allows partial restoration of intestinal microbiota in responders and the F.prausnitzii/E.coli ratio can provide a reliable indicator of response to anti-TNF in CD.
Subject(s)
Crohn Disease/microbiology , Gastrointestinal Microbiome/drug effects , Tumor Necrosis Factor Inhibitors/therapeutic use , Adult , Biomarkers , Case-Control Studies , Crohn Disease/drug therapy , Escherichia coli , Faecalibacterium prausnitzii , Female , Humans , Male , Middle Aged , Treatment Outcome , Tumor Necrosis Factor Inhibitors/pharmacology , Young AdultABSTRACT
OBJETIVO: Evaluar la utilidad de la determinación de concentraciones séricas (Cs) de adalimumab (ADA) como factor predictor de la adherencia al fármaco medida a través de la tasa de posesión de medicación (TPM) y del test de Morisky Green (MG) en pacientes con enfermedades crónicas inflamatorias. MATERIAL Y MÉTODO: Diseño prospectivo, descriptivo de cohortes. CRITERIOS DE INCLUSIÓN: pacientes adultos con artropatías inflamatorias (AI) o enfermedad inflamatoria intestinal (EII) en tratamiento con ADA. Criterios de exclusión: pacientes con anticuerpos anti-ADA. VARIABLES: sexo, edad, diagnóstico, pauta posológica, Cs (μg/ml), TPM (TPM ≥ 80% adherentes), y resultado del test de MG (no adherente o adherente). El análisis estadístico se realizó mediante STATA v13.0. RESULTADOS: Cuarenta y cinco pacientes (23 mujeres) con edad de 52,22 (14,39) años, 17 EII (37,78%), 26 AI (57,78%) y 2 con ambas enfermedades (4,44%) tratados con ADA cada 14 días (42/45,93,33%) o cada 7 días (3/45;6,67%). Se detectaron Cs infraterapéuticas en el 22,22% pacientes (10/45): el 10% (1/10) se clasifican como no adherentes y el 90% (9/10) como adherentes según MG y TPM. La Cs con la TPM, así como los métodos indirectos entre sí (TPM y MG) presentaron un índice de acuerdo débil, siendo la asociación ligeramente superior al relacionar los métodos indirectos entre sí (0,244 vs. 0,378). CONCLUSIÓN: La determinación de Cs de ADA presenta, por sí sola, una utilidad limitada en la detección de pacientes no adherentes
OBJECTIVE: to evaluate the usefulness of serum concentrations (Sc) of adalimumab (ADA) as a predictor of medication adherence using the medication possession ratio (MPR) and Morisky Green test (MGT) in patients with chronic inflammatory diseases. MATERIAL AND METHOD: Design a prospective descriptive cohort study. Inclusion criteria: adult patients diagnosed with inflammatory arthropathy (IA) or inflammatory bowel disease (IBD) treated with ADA. Exclusion criteria: positive anti-adalimumab antibody. VARIABLES: sex, age, diagnosis, dosage regimen, Sc (mg/mL), MPR (MPR ≥ 80% adherent) and MGT (non-adherent or adherent). Statistical analysis was performed using STATA v13.0. RESULTS: Forty-five patients (23 women) with an age of 52.22 (14.39) years, 17 IBD (37.78%), 26 IA (57.78%) and 2 with both conditions (4.44%) treated with 40mg ADA every 14 days (42/45; 93.33%) or every 7 days (3/45; 6.67%). We detected subtherapeutic Sc in 22.22% of patients (10/45); 10% (1/10) were classified as non-adherent and 90% (9/10) as adherent according to MGT and MPR. The quantification of Sc shows weak agreement with MPR, as was the case with the indirect methods of each (MPR and MGT). The association was slightly greater when the indirect methods were compared to each other (0.244 vs. 0.378). CONCLUSION: the determination of Sc of ADA alone has limited utility in the detection of non-adherent patients
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Adalimumab/administration & dosage , Adalimumab/adverse effects , Arthritis, Rheumatoid/drug therapy , Treatment Adherence and Compliance , Chronic Disease/drug therapy , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Prospective Studies , Adalimumab/pharmacokineticsABSTRACT
OBJECTIVE: to evaluate the usefulness of serum concentrations (Sc) of adalimumab (ADA) as a predictor of medication adherence using the medication possession ratio (MPR) and Morisky Green test (MGT) in patients with chronic inflammatory diseases. MATERIAL AND METHOD: Design a prospective descriptive cohort study. INCLUSION CRITERIA: adult patients diagnosed with inflammatory arthropathy (IA) or inflammatory bowel disease (IBD) treated with ADA. EXCLUSION CRITERIA: positive anti-adalimumab antibody. VARIABLES: sex, age, diagnosis, dosage regimen, Sc (mg/mL), MPR (MPR ≥ 80% adherent) and MGT (non-adherent or adherent). Statistical analysis was performed using STATA v13.0. RESULTS: Forty-five patients (23 women) with an age of 52.22 (14.39) years, 17 IBD (37.78%), 26 IA (57.78%) and 2 with both conditions (4.44%) treated with 40mg ADA every 14 days (42/45; 93.33%) or every 7 days (3/45; 6.67%). We detected subtherapeutic Sc in 22.22% of patients (10/45); 10% (1/10) were classified as non-adherent and 90% (9/10) as adherent according to MGT and MPR. The quantification of Sc shows weak agreement with MPR, as was the case with the indirect methods of each (MPR and MGT). The association was slightly greater when the indirect methods were compared to each other (0.244 vs. 0.378). CONCLUSION: the determination of Sc of ADA alone has limited utility in the detection of non-adherent patients.