Safety of Biological Therapy in Children With Inflammatory Bowel Disease.

OBJECTIVES: Retrospective, observational, single-center, cohort study investigating the safety profile of biological therapy in children with inflammatory bowel disease (IBD). METHODS: Retrospective, observational, cohort study of pediatric patients with IBD, receiving infliximab, adalimumab, vedolizumab, or ustekinumab for at least 2 months. Data related to the immediate and delayed adverse events (AEs) were collected, focusing on the reaction type and severity, the time of onset, the outcome and the temporary or definitive therapy discontinuation secondary to the AE. Number of suspected and confirmed coronavirus disease-209 (COVID-19) cases and their outcomes, as well as flu vaccination coverage were collected. RESULTS: One hundred eighty-five children were included (101 [55%] CD, 82 [44%] UC, and 2 [1%] IBDU): 149 received infliximab (IFX) (81%), 88 (48%) adalimumab (ADA), 18 (21%) vedolizumab, and 4 (2%) ustekinumab. The overall AE rates were 49%, 67% of whom likely medication-related. Eleven (6%) patients experienced more than 1 AE, 18 patients (10%) presented an immediate reaction, and 82 (45%) a delayed AE. Among the 90 patients experiencing at least 1 AE, 97% had mild-to-moderate AEs. Only 4 SAEs were reported (4%). Treatment discontinuation because of AE occurred in 25 patients (14%). Four COVID-19 cases were reported, all with a mild course. CONCLUSIONS: Our findings confirm a good safety profile of biologics. Infusion reactions to IFX administration remain one of the main issues, significantly linked to its immunogenicity and consequently with an impact on its efficacy and durability.

Efficacy of adalimumab as second-line therapy in a pediatric cohort of Crohn's disease patients who failed infliximab therapy: the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition experience.

BACKGROUND: Adalimumab (Ada) treatment is an available option for pediatric Crohn's disease (CD) and the published experience as rescue therapy is limited. OBJECTIVES: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. METHODS: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. RESULTS: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3-11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. CONCLUSION: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients.

Biological therapy in a pediatric Crohn disease population at a referral center.

OBJECTIVE: The antitumor necrosis factor α (TNFα) antibodies infliximab and adalimumab are effective in inducing and maintaining remission in pediatric patients with Crohn disease (CD). The aim of the study was to evaluate the long-term efficacy and safety of biological therapy in pediatric patients with CD followed at a referral center. METHODS: This work is a retrospective observational study enrolling patients with CD treated with infliximab or adalimumab beyond the induction protocol. The patients' data were collected from the unit's IBD database (maximum follow-up evaluation after 36 months of treatment). The efficacy was evaluated by the Pediatric Crohn Disease Activity Index score and by analysis of the cumulative probability of continuing therapy; the safety was assessed in terms of adverse events. RESULTS: We enrolled 78 patients; the mean therapy duration was 27.2 ± 16.7 months, and the mean age at enrollment was 15 ± 3.1 years. The Kaplan-Meier analysis showed a cumulative probability of continuing therapy of 81%, 54%, and 33% at 1, 2, and 3 years, respectively, from the introduction of therapy. No association between the patients' baseline characteristics and the long-term outcome was found. The evaluation of the concomitant therapy with immunomodulators and anti-TNFα therapy versus anti-TNFα alone did not show a different outcome. No serious adverse events were recorded. CONCLUSIONS: The study indicates that biological therapy is effective and safe in pediatric patients with CD in a longer follow-up period. The response to treatment was not influenced by the patients' baseline characteristics or by the immunomodulator association.

Advances in the medical management of paediatric IBD.

IBD includes two classic entities, Crohn's disease and ulcerative colitis, and a third undetermined form (IBD-U), characterized by a chronic relapsing course resulting in a high rate of morbidity and impaired quality of life. Children with IBD are vulnerable in terms of growth failure, malnutrition and emotional effects. The aims of therapy have now transitioned from symptomatic control to the achievement of mucosal healing and deep remission. This type of therapy has been made possible by the advent of disease-modifying drugs, such as biologic agents, which are capable of interrupting the inflammatory cascade underlying IBD. Biologic agents are generally administered in patients who are refractory to conventional therapies. However, there is growing support that such agents could be used in the initial phases of the disease, typically in paediatric patients, to interrupt and cease the inflammatory process. Until several years ago, most therapeutic programmes in paediatric patients with IBD were borrowed from adult trials, whereas paediatric studies were often retrospective and uncontrolled. However, guidelines on therapeutic management of paediatric IBD and controlled, prospective, randomized trials including children with IBD have now been published. Here, the current knowledge concerning treatment options for children with IBD are reported. We also highlight the effectiveness and safety of new therapeutic advances in these paediatric patients.