Canakinumab for the treatment of autoinflammatory very early onset- inflammatory bowel disease
IntroductionTherapeutic options are critically needed for children with refractory very early onset inflammatory bowel disease (VEO-IBD). Our aim was to evaluate clinical response to canakinumab, an anti-IL-1β monoclonal antibody, in patients with VEO-IBD whose phenotype resembles those with monogen...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.972114/full |
| _version_ | 1818021348278009856 |
|---|---|
| author | Eliana Shaul Máire A. Conrad Máire A. Conrad Noor Dawany Trusha Patel Trusha Patel Megan C. Canavan Alyssa Baccarella Sarah Weinbrom Daniel Aleynick Kathleen E. Sullivan Kathleen E. Sullivan Judith R. Kelsen Judith R. Kelsen |
| author_facet | Eliana Shaul Máire A. Conrad Máire A. Conrad Noor Dawany Trusha Patel Trusha Patel Megan C. Canavan Alyssa Baccarella Sarah Weinbrom Daniel Aleynick Kathleen E. Sullivan Kathleen E. Sullivan Judith R. Kelsen Judith R. Kelsen |
| author_sort | Eliana Shaul |
| collection | DOAJ |
| description | IntroductionTherapeutic options are critically needed for children with refractory very early onset inflammatory bowel disease (VEO-IBD). Our aim was to evaluate clinical response to canakinumab, an anti-IL-1β monoclonal antibody, in patients with VEO-IBD whose phenotype resembles those with monogenic autoinflammatory disease.MethodsThis is a single center retrospective study of patients with VEO-IBD with autoinflammatory phenotype (AIP) in the absence of identified monogenic disease treated with canakinumab for >6 months. AIP was defined as confirmed IBD with associated signs of systemic inflammation in the absence of infection, including leukocytosis, markedly elevated inflammatory markers, and extraintestinal manifestations (recurrent fevers, oral ulcers, arthritis). Primary outcomes included clinical response in disease activity indices after 6 months of therapy. Secondary outcomes included rate of AIP signs and symptoms, growth, surgery, steroid use, hospitalizations, and adverse events.ResultsNineteen patients were included: 47% with infantile onset, 58% classified as IBD-U, and 42% classified as CD. At baseline, 37% were biologic naïve, and canakinumab was used as dual therapy in 74% of patients. Clinical response was achieved in 89% with statistically significant improvement in PCDAI and PUCAI. Clinical remission was achieved in 32% of patients. There was significant improvement in the clinical manifestations of AIP and the biochemical markers of disease. Number of hospitalizations (p<0.01) and length of stay (p<0.05) decreased. Growth improved with median weight-for-length Z-score increasing from -1.01 to 1.1 in children less than 2 years old. There were minimal adverse events identified during the study period.ConclusionCanakinumab may be an effective and safe treatment for a subset of children with VEO-IBD with AIP, as well as older patients with IBD. This study highlights the importance of a precision medicine approach in children with VEO-IBD. |
| first_indexed | 2024-04-14T08:16:52Z |
| format | Article |
| id | doaj.art-b6ac90a53ff746f68ce9c1bd64b099f7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T08:16:52Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b6ac90a53ff746f68ce9c1bd64b099f72022-12-22T02:04:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.972114972114Canakinumab for the treatment of autoinflammatory very early onset- inflammatory bowel diseaseEliana Shaul0Máire A. Conrad1Máire A. Conrad2Noor Dawany3Trusha Patel4Trusha Patel5Megan C. Canavan6Alyssa Baccarella7Sarah Weinbrom8Daniel Aleynick9Kathleen E. Sullivan10Kathleen E. Sullivan11Judith R. Kelsen12Judith R. Kelsen13Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United StatesDivision of Allergy and Immunology, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United StatesIntroductionTherapeutic options are critically needed for children with refractory very early onset inflammatory bowel disease (VEO-IBD). Our aim was to evaluate clinical response to canakinumab, an anti-IL-1β monoclonal antibody, in patients with VEO-IBD whose phenotype resembles those with monogenic autoinflammatory disease.MethodsThis is a single center retrospective study of patients with VEO-IBD with autoinflammatory phenotype (AIP) in the absence of identified monogenic disease treated with canakinumab for >6 months. AIP was defined as confirmed IBD with associated signs of systemic inflammation in the absence of infection, including leukocytosis, markedly elevated inflammatory markers, and extraintestinal manifestations (recurrent fevers, oral ulcers, arthritis). Primary outcomes included clinical response in disease activity indices after 6 months of therapy. Secondary outcomes included rate of AIP signs and symptoms, growth, surgery, steroid use, hospitalizations, and adverse events.ResultsNineteen patients were included: 47% with infantile onset, 58% classified as IBD-U, and 42% classified as CD. At baseline, 37% were biologic naïve, and canakinumab was used as dual therapy in 74% of patients. Clinical response was achieved in 89% with statistically significant improvement in PCDAI and PUCAI. Clinical remission was achieved in 32% of patients. There was significant improvement in the clinical manifestations of AIP and the biochemical markers of disease. Number of hospitalizations (p<0.01) and length of stay (p<0.05) decreased. Growth improved with median weight-for-length Z-score increasing from -1.01 to 1.1 in children less than 2 years old. There were minimal adverse events identified during the study period.ConclusionCanakinumab may be an effective and safe treatment for a subset of children with VEO-IBD with AIP, as well as older patients with IBD. This study highlights the importance of a precision medicine approach in children with VEO-IBD.https://www.frontiersin.org/articles/10.3389/fimmu.2022.972114/fullcanakinumabvery early onset-inflammatory bowel diseaseinterleukin-1pediatricautoinflammatory |
| spellingShingle | Eliana Shaul Máire A. Conrad Máire A. Conrad Noor Dawany Trusha Patel Trusha Patel Megan C. Canavan Alyssa Baccarella Sarah Weinbrom Daniel Aleynick Kathleen E. Sullivan Kathleen E. Sullivan Judith R. Kelsen Judith R. Kelsen Canakinumab for the treatment of autoinflammatory very early onset- inflammatory bowel disease Frontiers in Immunology canakinumab very early onset-inflammatory bowel disease interleukin-1 pediatric autoinflammatory |
| title | Canakinumab for the treatment of autoinflammatory very early onset- inflammatory bowel disease |
| title_full | Canakinumab for the treatment of autoinflammatory very early onset- inflammatory bowel disease |
| title_fullStr | Canakinumab for the treatment of autoinflammatory very early onset- inflammatory bowel disease |
| title_full_unstemmed | Canakinumab for the treatment of autoinflammatory very early onset- inflammatory bowel disease |
| title_short | Canakinumab for the treatment of autoinflammatory very early onset- inflammatory bowel disease |
| title_sort | canakinumab for the treatment of autoinflammatory very early onset inflammatory bowel disease |
| topic | canakinumab very early onset-inflammatory bowel disease interleukin-1 pediatric autoinflammatory |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.972114/full |
| work_keys_str_mv | AT elianashaul canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT maireaconrad canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT maireaconrad canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT noordawany canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT trushapatel canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT trushapatel canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT meganccanavan canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT alyssabaccarella canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT sarahweinbrom canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT danielaleynick canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT kathleenesullivan canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT kathleenesullivan canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT judithrkelsen canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease AT judithrkelsen canakinumabforthetreatmentofautoinflammatoryveryearlyonsetinflammatoryboweldisease |