Dual Biologic Therapy in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Retrospective Study

Background: Inflammatory bowel diseases in children are characterized by a wide variety of symptoms and often a severe clinical course. In the treatment, we aimed to induce and maintain remission. We focused on assessing the efficacy and safety of the concomitant use of two biologic therapies including: anti-TNF (infliximab, adalimumab) vedolizumab and ustekinumab in a refractory pediatric IBD cohort. Methods: Fourteen children (nine ulcerative colitis, one ulcerative colitis/IBD-unspecified, four Crohn’s disease) with a disease duration of 5.2 (8 months–14 years) years, initiated dual therapy at an age of 11.7 (3–17) years after failure of monotherapy with a biological drug. Five patients (36%) were treated with vedolizumab/adalimumab (VDZ + ADA), five (36%) with ustekinumab/adalimumab (UST + ADA), and three (21%) with infliximab/vedolizumab (IFX + VDZ). One patient (7%) was switched from a combination of vedolizumab and adalimumab to ustekinumab and adalimumab during follow-up. Results: A clinical improvement was obtained in ten children (73%; 5 UC, 1 UC/IBD-unspecified, 4 CD) on the PCDAI/PUCAI scale after 4 months of a second biological drug being added. The median fecal calprotectin decreased from 1610 µg/g (140–10,100) to 586 µg/g (5–3410; p = 0.028) between baseline and 4 months. Conclusions: Our clinical experience suggests that dual therapy may be an option for pediatric patients with moderate and severe courses of IBD with limited therapeutic option

Experience with biosimilar infliximab (CT-P13) in paediatric patients with inflammatory bowel diseases

Infliximab was the first monoclonal antibody used in the treatment of inflammatory bowel disease (IBD). Over several years, this antitumour necrosis factor (TNF) treatment proved its efficacy in both induction and maintenance therapy. In many cases this biological treatment stopped the progression of the disease, probably also decreasing morbidity and hospitalization rates, and improving patients’ comfort. When the patent on infliximab started to expire, the first biosimilar of a monoclonal antibody was introduced onto the pharmacological market. Biosimilar infliximab was studied in rheumatology and proved a high similarity to the reference drug. Based on extrapolation, biosimilars were approved to treat adult and paediatric IBD patients. Biosimilar infliximab, mainly because of its lower cost, has started to be in common use in Europe. The first studies have shown a similar efficacy and safety profile in comparison with reference drug. Biosimilar infliximab is raising hopes for improving the availability of this effective treatment

Effect of the Crohn’s Disease Exclusion Diet (CDED) on the Fecal Calprotectin Level in Children with Active Crohn’s Disease

(1) Background: The CDED + PEN (partial enteral nutrition) is a promising method of nutritional treatment in active Crohn’s disease (CD). An increase in fecal calprotectin (FCP) level—a marker of mucosal inflammation—happens to be the first evidence of Crohn’s disease exacerbation that appears ahead of clinical symptoms and usually co-exists with them. In this study, we present our own experience with using the CDED + PEN in the treatment of children with CD and an increased FCP level. (2) Methods: In total, 48 children (male/female: 27/21) aged 4–17 years (median value = 13.43; IQR = 4.00) were treated with CDED + PEN between June 2019 and July 2021. The main inclusion criteria for the study was active CD defined as an FCP level ≥ 250.00 µg/g. Patients with severe clinical manifestation of CD (PCDAI >40.00), as well as ones who started any new concomitant CD treatment later than at least 4 weeks before the start of dietary intervention, were excluded from the analysis. The PCDAI and fecal calprotectin level were assessed at weeks 0 and 12. The primary endpoint was ITT normalization of FCP level, i.e., a result < 250.00 µg/g at week 12. The Wilcoxon Matched Pairs Test was used for statistical analysis. (3) Results: The normalization of the FCP level was obtained in 17 children (35.42%) and an FCP level decrease of at least 50% occurred in 26 patients (54.17%). The reduction in fecal calprotectin level between week 0 and week 12 was statistically significant with a median value of 1045.00 µg/g; IQR = 1188.00, and 363.00 µg/g; IQR = 665.00, respectively (p < 0.05). Among 29 patients who were not in clinical remission at baseline, 16 (55.17%) achieved clinical remission (PCDAI < 10.00) at week 12 and 20 (68.97%) obtained a clinical response defined as at least a 12.50 point drop in PCDAI or remission. In this group, the reduction in PCDAI between baseline and week 12 was statistically significant (median value = 20.00 points; IQR = 7.50 and 5.00 points; IQR = 5.00, respectively (p < 0.05)). All patients with a normal FCP level at week 12 were in clinical remission and 16 (94.13%) of them had a normal CRP (C-reactive protein) value. In 10 children (20.83%) the full course of 12 weeks with CDED + PEN was not completed or the concomitant therapy had been started before week 12 due to the lack of efficacy/intolerance of nutritional treatment. (4) Conclusions: The 12-week course of treatment with the CDED + PEN has a beneficial effect on the fecal calprotectin level in children with active CD. The dietary intervention led to a significant decrease in the FCP level in the studied group and to the normalization of this parameter in every third patient