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BACKGROUND AND AIM: There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease. METHODS: All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naïve to ADA and naïve to anti-tumor necrosis factors; group B, naïve to ADA and previously exposed to anti-tumor necrosis factors; and group C: switched from ADA originator to ABP 501. RESULTS: A total of 559 patients (median age 39 years; Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six serious adverse events occurred in 36 patients (6.4%; incidence rate [IR]: 8.9 per 100 person-years [PY]). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY; IR ratio = 3.61; P < 0.001) and among patients in group B compared with group C (16.4 vs 4.8 per 100 PY; IR ratio = 3.42; P = 0.041). Among ADA-naïve patients (group A + B), 188 (85.8%) had a clinical response after 12 weeks, including 165 (75.3%) who achieved steroid-free remission. Higher treatment persistence estimates were reported for patients in group C compared with groups A and B (log-rank P < 0.001). CONCLUSIONS: Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.
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Adalimumab , Biosimilares Farmacéuticos , Enfermedades Inflamatorias del Intestino , Inhibidores del Factor de Necrosis Tumoral , Adalimumab/efectos adversos , Adalimumab/uso terapéutico , Adulto , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
BACKGROUND: The utilization of anti-tumor necrosis factor-α (anti-TNF-α) biosimilars in inflammatory bowel disease (IBD) is constantly increasing. However, pediatric data are limited. This study aimed to assess the effectiveness and safety of adalimumab biosimilar (ADL-BioS) in pediatric IBD patients. METHODS: All consecutive pediatric IBD patients from the Sicilian Network for Inflammatory Bowel Disease cohort treated with ADL-BioS from 2019 to 2021 were recruited. Remission at weeks 14 and 52, treatment persistence, and adverse events were the endpoints of this study. Factors associated with clinical remission and treatment persistence were examined. RESULTS: There were 41 patients in total. Nine (22%) patients were switched from the reference product to ADL-BioS. Two patients had multiple switches. Eleven months was the median follow-up period. Clinical remission was attained by 70.7% and 72.0% of patients on weeks 14 and 52, respectively. Four (9.8%) adverse events occurred (10.1/100 person-year). Treatment persistence was 85.4% at 1 and 2 years. Patients with a longer duration of disease had a higher probability of stopping their treatment (p = 0.036). CONCLUSIONS: This is the first real-world study that particularly addresses the use of ADL-BioS in pediatric IBD. With high rates of treatment persistence and a low frequency of non-serious side effects, ADL-BioS seems to be effective.
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BACKGROUND: Studies have indicated an association between cesarean section (CS), especially elective CS, and an increased risk of celiac disease (CD), but the conclusions of other studies are contradictory. The primary aim of this study (CD-deliver-IT) was to evaluate the rate of CS in a large population of CD patients throughout Italy. METHODS: This national multicenter retrospective study was conducted between December 2020 and November 2021. The coordinating center was the Pediatric Gastroenterology and Liver Unit of Policlinico Umberto I, Sapienza, University of Rome, Lazio, Italy. Eleven other referral centers for CD have participated to the study. Each center has collected data on mode of delivery and perinatal period of all CD patients referring to the center in the last 40 years. RESULTS: Out of 3,259 CD patients recruited in different Italian regions, data on the mode of delivery were obtained from 3,234. One thousand nine hundred forty-one (1,941) patients (60%) were born vaginally and 1,293 (40%) by CS (8.3% emergency CS, 30.1% planned CS, 1.5% undefined CS). A statistically significant difference was found comparing median age at time of CD diagnosis of patients who were born by emergency CS (4 years, CI 95% 3.40-4.59), planned CS (7 years, CI 95% 6.02-7.97) and vaginal delivery (6 years, CI 95% 5.62-6.37) (log rank p < 0.0001). CONCLUSIONS: This is the first Italian multicenter study aiming at evaluating the rate of CS in a large population of CD patients through Italy. The CS rate found in our CD patients is higher than rates reported in the general population over the last 40 years and emergency CS seems to be associated with an earlier onset of CD compared to vaginal delivery or elective CS in our large nationwide retrospective cohort. This suggests a potential role of the mode of delivery on the risk of developing CD and on its age of onset, but it is more likely that it works in concert with other perinatal factors. Further prospective studies on other perinatal factors potentially influencing gut microbiota are awaited in order to address heavy conflicting evidence reaming in this research field.
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Enfermedad Celíaca , Cesárea , Parto Obstétrico , Humanos , Italia/epidemiología , Enfermedad Celíaca/epidemiología , Estudios Retrospectivos , Femenino , Parto Obstétrico/estadística & datos numéricos , Cesárea/estadística & datos numéricos , Embarazo , Prevalencia , Masculino , Preescolar , Niño , AdultoRESUMEN
In pediatric patients with Inflammatory Bowel Disease renal parenchymal disease is infrequent. There are only two reports about the association between IgA Nephropathy and Pediatric Crohn Disease. IgA Nephropathy is a rather uncommon complication of Tumor Necrosis Factor-alpha (TNF-α) inhibition. We describe a case of IgA Nephropathy which has arisen in a 11-year-old child 2 years after Crohn disease diagnosis, during therapy with anti-TNF-α. An ileal e jejunal Crohn disease was diagnosed at 9 years old, initially treated with prednisone, followed by biological therapy with anti-TNF-α (Adalimumab) due to severe disease activity, with gradual improvement of clinical conditions until clinical remission is achieved. Two years after the diagnosis, the child suddenly presented macroscopic hematuria. Subsequent laboratory examinations showed acute renal failure. So kidney biopsy was performed and IgA Nephropathy diagnosis was made. Adalimumab was discontinued and the child has been treated with steroids for sixth months associated with angiotensin-converting enzyme inhibitor resulted in clinical improvement over the following year and remission was maintained. To our knowledge the association of IgA Nephropathy and pediatric IBD during therapy with anti-TNF-α has never been reported. Careful monitoring of renal function, proteinuria, and autoantibodies is advised in patients treated with anti-TNF-α agents.
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Enfermedad de Crohn , Glomerulonefritis por IGA , Adalimumab/efectos adversos , Niño , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Glomerulonefritis por IGA/inducido químicamente , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/tratamiento farmacológico , Humanos , Infliximab , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVE: To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD). METHODS: A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes. RESULTS: Eighty-seven patients [Crohn's disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations ( P = 0.018) and in those who were nonnaïve to anti-TNF-α ( P = 0.027). CONCLUSION: This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events.
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Biosimilares Farmacéuticos , Colitis Ulcerosa , Enfermedad de Crohn , Infliximab , Biosimilares Farmacéuticos/uso terapéutico , Niño , Enfermedad Crónica , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Humanos , Infliximab/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
BACKGROUND: The association between inflammatory bowel disease (IBD) and immune thrombocytopenia (ITP) is still uncertain. In this multicenter retrospective study, the coexistence of both diseases was investigated in children diagnosed from 1 January 2000 to 31 December 2019. METHODS: Clinical characteristics of both IBD and ITP, onset of disorders, and patient's response to treatment were collected through a structured form sent to 55 Italian pediatric referring centers for hematological disorders. RESULT: Centers responded to the survey and reported the coexistence of IBD and ITP in 14 children. The first diagnosis was ITP in 57.1% and IBD in 35.7% of patients: it was simultaneous in 7.1%. IBD was classified as ulcerative colitis (57.1%), Crohn disease (35.7%), and unclassified (7.1%). No therapy for IBD other than steroids had any effect on ITP course. Colectomy resulted in recovery from ITP in 1 of the 2 patients surgically treated. ITP was always mild but turned to be chronic in half of patients. CONCLUSIONS: In all patients, ITP was mild without any evident impact on IBD severity, but the incidence of chronic ITP seems to be higher than what is usually observed in the pediatric age group. Colectomy had unpredictable effects on ITP.
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BACKGROUND: Adult patients with both inflammatory bowel disease (IBD) and celiac disease (CeD) have peculiar phenotypic features. This study aimed at describing the characteristics and natural history of children with both IBD and CeD. METHODS: This was a case-control study based on a national registry. Cases included children diagnosed with both IBD and CeD. Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case. Inflammatory bowel disease phenotype and natural history, comprising growth and pubertal development, were compared between groups. RESULTS: Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97-8.37; P = 0.04). Ileocolonic localization (46.1% vs 73.1%), treatment with azathioprine (46.2% vs 71.2%), and anti-TNF biologics (46.2% vs 69.2%) were less common in patients with Crohn's disease and CeD than in patients with Crohn's disease alone. Patients with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%). Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24; 95% CI, 1.13-33.0; P = 0.02) and CeD alone (14.9% vs 1.1%; P = 0.002). CONCLUSIONS: Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.
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Enfermedad Celíaca , Enfermedades Inflamatorias del Intestino , Enfermedades Autoinmunes/complicaciones , Estudios de Casos y Controles , Enfermedad Celíaca/complicaciones , Niño , Colectomía , Colitis Ulcerosa/complicaciones , Enfermedad de Crohn/complicaciones , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Fenotipo , Pubertad Tardía/etiología , Inhibidores del Factor de Necrosis TumoralRESUMEN
BACKGROUND: Biological therapies have modified the disease course of pediatric inflammatory bowel disease (IBD) and are routinely used in clinical practice. Our observational study aims to evaluate effectiveness and safety of biologics in IBD. METHOD: Clinical benefit and safety data of 93 children with IBD, receiving biologics (Infliximab - IFX, Adalimumab - ADA, Golimumab - GOL) from January 2013 to December 2017, were extracted from the cohort of the Sicilian Network of IBD. RESULTS: Among 87 children aged 7-17 years (63 Crohn's disease [CD], 24 Ulcerative colitis [UC]), 101 out of 108 biologic treatments were considered. Evaluation of 74 biologic treatments in CD patients at 26, 52, 104 weeks showed clinical benefit rates of 84.2%, 93.3%, 66.7% with IFX (n= 38) and 88.9%, 84.4%, 65.2% with ADA (n= 36). Biologic treatments (n=27) evaluated in the UC group at 26, 52, 104 weeks, led to clinical benefit rates of 85.7%, 83.3%, 50% in IFX subgroup (n=21) and 40%, 50%, 33% in the ADA subgroup (n=5), respectively. One patient treated with GOL showed 100% clinical benefit at 26 and 52 weeks. Overall adverse events (AEs) rate was 9.25%. Six younger children, <6 years, receiving 8 treatments (4 ADA, 4 IFX) presented a clinical remission rate of 75% at 12 weeks and 25% at 52 weeks. AEs rate was 25% in this group. CONCLUSION: Our data show that biologic therapy in children, even at a younger age, is effective in allowing long-term remission with a good safety profile.
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Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Productos Biológicos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Infliximab/uso terapéutico , Adolescente , Niño , Femenino , Humanos , Masculino , Estudios Retrospectivos , Sicilia , Resultado del TratamientoRESUMEN
BACKGROUND: No real-life study on the comparative effectiveness of Vedolizumab (VDZ), Adalimumab (ADA), and Golimumab (GOL) in ulcerative colitis (UC) is currently available. AIMS: To compare the effectiveness of the three biologics in consecutive patients with UC. METHODS: A three-arms propensity score-adjusted analysis was performed using the Inverse Probability of Treatment Weighting method. RESULTS: 463 treatments (VDZ: nâ¯=â¯187; ADA: nâ¯=â¯168; GOL: nâ¯=â¯108) were included (median follow-up: 47.6 weeks). At 12 weeks (nâ¯=â¯463), a steroid-free remission was reported in 24.1% patients in the VDZ group, in 33.3% patients in the ADA group, and in 30.6% patients in the GOL group (pâ¯=â¯n.s. for all comparisons). At 52 weeks (nâ¯=â¯377), a steroid-free remission was reported in 51.5% patients in the VDZ group, in 31.2% patients in the ADA group, and in 29.4% patients in the GOL group (pâ¯=â¯0.002 for VDZ vs. ADA, pâ¯=â¯0.001 for VDZ vs. GOL, pâ¯=â¯n.s. for ADA vs. GOL). Cox survival analysis demonstrated that patients treated with VDZ had reduced probability of treatment discontinuation compared to those treated with ADA (HR: 0.42, 95% CI 0.28-0.64, p < 0.001) and GOL (HR: 0.30, 95% CI 0.19-0.46, p < 0.001), while patients treated with ADA had reduced risk of treatment discontinuation compared to those treated with GOL (HR: 0.71, 95% CI 0.50-1.00, pâ¯=â¯0.048). CONCLUSIONS: VDZ was superior to ADA and GOL at 52 weeks and as treatment persistence, while ADA showed a superior treatment persistence compared to GOL.
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Adalimumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Adulto , Análisis Costo-Beneficio , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: There is an unmet need to better understand the effectiveness of different biologics in inflammatory bowel diseases. We aimed at performing a multicentre, real-life comparison of the effectiveness of infliximab [IFX] and adalimumab [ADA] in Crohn's disease [CD]. METHODS: Data of consecutive patients with CD treated with IFX and ADA from January 2013 to May 2017 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. We used propensity score-matching accounting for the main baseline characteristics in TNF-α inhibitor-naïve and non-naïve patients. RESULTS: A total of 632 patients [735 total treatments] were included. Among naïve patients, a clinical benefit [the sum of steroid-free remission plus clinical response] was achieved in 81.8% patients treated with ADA and in 77.6% patients treated with IFX (adjusted odds ratio [OR]: 1.23, 95% CI 0.63-2-44, p = 0.547] at 12 weeks; after 1 year, a clinical benefit was achieved in 69.2% of patients treated with ADA and in 64.5% patients treated with IFX [adjusted OR: 1.10, 95% CI 0.61-1.96, p = 0.766]. Among non-naïve patients, a clinical benefit was achieved in 61.7% of patients treated with ADA and in 68.1% of patients treated with IFX [adjusted OR: 0.72, 95% CI 0.21-2.44, p = 0.600] at 12 weeks; after 1 year, a clinical benefit was achieved in 48.9% of patients treated with ADA and in 40.4% patients treated with IFX [adjusted OR: 1.23, 95% CI 0.54-2.86, p = 0.620]. CONCLUSIONS: In this propensity score-matched comparison of ADA and IFX in CD, both drugs showed high rates of clinical benefit, without significant differences between them.