Ruth Garcia-Romero1, José Miguel Martinez de Zabarte Fernandez2, Gemma Pujol-Muncunill3, Ester Donat-Aliaga4, Oscar Segarra-Cantón5, Iñaki Irastorza-Terradillos6, Enrique Medina-Benitez7, Carlos José Ruiz-Hernández8, Marta Carrillo-Palau9, Ignacio Ros-Arnal10, Alejandro Rodriguez-Martínez11, Laura Escartin-Madurga12, Carolina Gutiérrez-Junquera13, Saioa Vicente-Santamaría14, Marta Velasco Rodriguez-Belvis15, Sonia Fernández-Fernández16, José Ramón Alberto-Alonso17, Montserrat Montraveta18, Ricardo Torres-Peral19, María Navalon-Rubio20, Víctor Manuel Navas-López21, Javier Martin de Carpi3. 1. Paediatric Gastroenterology, Hepatology and Nutrition, Paediatric University Hospital Miguel Servet, Zaragoza, Spain. ruthgarciaromero@yahoo.es. 2. Paediatric Gastroenterology and Nutrition, Hospital Obispo Polanco, Teruel, Spain. 3. Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain. 4. Paediatric Gastroenterology, Hepatology and Nutrition, Polytechnic University Hospital La Fe, Valencia, Spain. 5. Paediatric Gastroenterology, Hepatology and Nutrition, Mother-Child University Hospital, Vall Hebrón, Barcelona, Spain. 6. Paediatric Gastroenterology, Hepatology and Nutrition, University Hospital of Cruces, Barakaldo, Spain. 7. Paediatric Gastroenterology, Hepatology and Nutrition Unit, University Hospital 12 de Octubre, Madrid, Spain. 8. Paediatric Gastroenterology and Nutrition, Department of Paediatrics, Hospital Parc Taulí, Sabadell, Spain. 9. Department of Gastroenterology, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain. 10. Paediatric Gastroenterology, Hepatology and Nutrition, Paediatric University Hospital Miguel Servet, Zaragoza, Spain. 11. Paediatric Gastroenterology, Hepatology and Nutrition, University Hospital Virgen del Rocío, Sevilla, Spain. 12. Paediatric Gastroenterology, Hepatology and Nutrition, University Clinic Hospital Lozano Blesa, Zaragoza, Spain. 13. Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain. 14. Paediatric Gastroenterology, Hepatology and Nutrition, University Hospital Ramon y Cajal, Madrid, Spain. 15. Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Niño Jesús, Madrid, Spain. 16. Paediatric Gastroenterology, Hepatology and Nutrition, University Hospital Severo Ochoa, Leganés, Madrid, Spain. 17. Paediatric Gastroenterology, Hepatology and Nutrition, University Hospital Ntra. Sra. de Candelaria, Tenerife, Spain. 18. Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Germans Trias i Pujol, Badalona, Spain. 19. Paediatric Gastroenterology and Nutrition Unit, Department of Paediatrics, University Hospital Complex, Salamanca, Spain. 20. Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Virgen de la Arrixaca, Murcia, Spain. 21. Paediatric Gastroenterology and Nutrition Section, Regional University Hospital of Malaga, Málaga, Spain.
Abstract
Vedolizumab is a humanised monoclonal antibody that binds to integrin α4β7 expressed in T-cells, inhibiting its binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is specifically expressed in the small intestine and colon, playing a fundamental role in T-cell migration to the gastrointestinal tract. Vedolizumab has been shown to be effective in treating adults with inflammatory bowel disease; however, efficacy data for paediatric use are scarce. The objective of the present study was to assess the effectiveness and safety of vedolizumab for inducing and maintaining clinical remission in children with inflammatory bowel disease. We conducted a retrospective multicentre study of patients younger than 18 years with inflammatory bowel disease refractory to anti-tumour necrosis factor alpha (anti-TNF-α) drugs, who underwent treatment with vedolizumab. Clinical remission was defined as a score < 10 points in the activity indices. We included 42 patients, 22 of whom were male (52.3%), with a median age of 13.1 years (IQR 10.2-14.2) at the start of treatment. Of the 42 patients, 14 (33.3%) had Crohn's disease (CD) and 28 (66.7%) had ulcerative colitis (UC). At the start of treatment with vedolizumab, the Paediatric Crohn's Disease Activity Index was 36 (IQR 24-40) and the Paediatric Ulcerative Colitis Activity Index was 47 (IQR 25-65). All of them had received prior treatment with anti-TNF and 3 patients ustekinumab. At week 14, 69% of the patients responded to the treatment (57.1% of those with CD and 75% of those with UC; p=0.238), and 52.4% achieved remission (35.7% with CD and 60.7% with UC; p=0.126). At 30 weeks, the response rate was 66.7% (46.2% and 78.3% for CD and UC, respectively; p=0.049), and 52.8% achieved remission (30.8% and 65.2% for CD and UC, respectively; p=0.047). Among the patients with remission at week 14, 80% of the patients with CD and 84.5% of those with UC maintained the remission at 52 weeks. Adverse effects were uncommon and mild. Three patients (7.1%) presented headaches, 1 presented alopecia, 1 presented anaemia and 1 presented dermatitis. Conclusion: The results show that treatment with vedolizumab is a safe and effective option for achieving clinical remission in paediatric patients with inflammatory bowel disease with primary failure or loss of response to other treatments, especially in UC. What is Known: • Vedolizumab is effective in inducing and maintaining remission in adult patients with inflammatory bowel disease. • Most studies and clinical trials have been performed on adult populations, and there is currently no indication for paediatric populations. What is New: • Children with inflammatory bowel disease refractory to anti-TNF presented higher clinical remission rates than those published for adults. • There are few publications of this magnitude on paediatric populations treated with vedolizumab and with long-term follow-up (52 weeks).
Vedolizumab is a humanised monoclonal antibody that binds to integrin α4β7 expressed in T-cells, inhibiting its binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is specifically expressed in the small intestine and colon, playing a fundamental role in T-cell migration to the gastrointestinal tract. Vedolizumab has been shown to be effective in treating adults with inflammatory bowel disease; however, efficacy data for paediatric use are scarce. The objective of the present study was to assess the effectiveness and safety of vedolizumab for inducing and maintaining clinical remission in children with inflammatory bowel disease. We conducted a retrospective multicentre study of patients younger than 18 years with inflammatory bowel disease refractory to anti-tumour necrosis factor alpha (anti-TNF-α) drugs, who underwent treatment with vedolizumab. Clinical remission was defined as a score < 10 points in the activity indices. We included 42 patients, 22 of whom were male (52.3%), with a median age of 13.1 years (IQR 10.2-14.2) at the start of treatment. Of the 42 patients, 14 (33.3%) had Crohn's disease (CD) and 28 (66.7%) had ulcerative colitis (UC). At the start of treatment with vedolizumab, the Paediatric Crohn's Disease Activity Index was 36 (IQR 24-40) and the Paediatric Ulcerative Colitis Activity Index was 47 (IQR 25-65). All of them had received prior treatment with anti-TNF and 3 patients ustekinumab. At week 14, 69% of the patients responded to the treatment (57.1% of those with CD and 75% of those with UC; p=0.238), and 52.4% achieved remission (35.7% with CD and 60.7% with UC; p=0.126). At 30 weeks, the response rate was 66.7% (46.2% and 78.3% for CD and UC, respectively; p=0.049), and 52.8% achieved remission (30.8% and 65.2% for CD and UC, respectively; p=0.047). Among the patients with remission at week 14, 80% of the patients with CD and 84.5% of those with UC maintained the remission at 52 weeks. Adverse effects were uncommon and mild. Three patients (7.1%) presented headaches, 1 presented alopecia, 1 presented anaemia and 1 presented dermatitis. Conclusion: The results show that treatment with vedolizumab is a safe and effective option for achieving clinical remission in paediatric patients with inflammatory bowel disease with primary failure or loss of response to other treatments, especially in UC. What is Known: • Vedolizumab is effective in inducing and maintaining remission in adult patients with inflammatory bowel disease. • Most studies and clinical trials have been performed on adult populations, and there is currently no indication for paediatric populations. What is New: • Children with inflammatory bowel disease refractory to anti-TNF presented higher clinical remission rates than those published for adults. • There are few publications of this magnitude on paediatric populations treated with vedolizumab and with long-term follow-up (52 weeks).