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Lauren V Collen, Rapid Clinical Remission With Upadacitinib in a Pediatric Patient With Refractory Crohn’s Disease, Inflammatory Bowel Diseases, Volume 29, Issue 7, July 2023, Pages 1175–1176, https://doi.org/10.1093/ibd/izad048
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Lay Summary
A pediatric patient with Crohn’s disease refractory to anti-tumor necrosis factor therapy, vedolizumab, ustekinumab, and 6-mercaptopurine achieved rapid clinical remission with upadacitinib. This is the first report of successful use of upadacitinib in pediatric inflammatory bowel disease.
Case
A 12-year-old female patient with nonstricturing, nonpenetrating ileocolonic Crohn’s disease diagnosed at 6 years of age, refractory to anti-tumor necrosis factor (anti-TNF) therapy, vedolizumab, ustekinumab, 6-mercaptopurine, and ileocecectomy, was hospitalized with severe disease. At time of admission, she was having 10 stools per day, completely unformed, all containing blood. She was reporting significant abdominal pain and nocturnal symptoms and low energy, and had not attended school in over 1 month. Her Pediatric Crohn’s Disease Activity Index (PCDAI) score was 45, indicating severe disease activity. Laboratory values were as summarized in Table 1. Endoscopic restaging was performed on ustekinumab 90 mg every-4-week dosing and was notable for patchy, primarily left-sided colonic inflammation that was graded as severe, as well as for aphthae at the ileocolonic anastomosis. The patient was initiated on intravenous steroids and was transitioned to oral steroids as an outpatient, but after 2 weeks her PCDAI score was minimally improved at 42.5, reflecting ongoing severe disease. She had become reliant on tramadol for pain control and experienced significant school absenteeism. At this time, ustekinumab was discontinued and upadacitinib was initiated at 45 mg daily dosing. By 2 weeks after upadacitinib initiation, the patient was noticing improvement in symptoms. By 4 weeks after upadacitinib initiation, the patient was in clinical and biomarker remission, with PCDAI score of 0, was no longer using tramadol, and had returned to school. By 8 weeks after upadacitinib initiation, the patient had tapered off steroids completely and remained in clinical remission, tolerating decrease to 15 mg maintenance dosing. The patient did not experience any adverse effects during the observation period.
| . | Week 0 . | Week 4 . | Reference Range . |
|---|---|---|---|
| White blood cell count, 1000 cells/μL | 18.7a | 14.9a | 4.85-9.69 |
| Hemoglobin, g/dL | 13.1 | 13.2 | 11.4-14.7 |
| ESR, mm/h | 55a | 9 | 0-30 |
| ALT, units/L | 46a | 49a | 3-30 |
| Albumin, g/dL | 4.3 | 4.6 | 3.0-4.6 |
| CRP, mg/dL | 2.28a | <0.06 | ≤0.50 |
| Cholesterol, fasting | 171a | 182a | <170 (acceptable) 170-199 (borderline high) ≥200 (high) |
| Triglycerides, fasting | 97a | 55 | <90 (acceptable) 90-129 (borderline high) ≥130 (high) |
| HDL, fasting | 80.5 | 63.6 | <40—low 40-45—borderline ≥45 (acceptable) |
| Non-HDL cholesterol | 90 | 118 | <120 (acceptable) 120-144 (borderline high) ≥145 (high) |
| LDL, fasting | 71 | 107 | <110 (acceptable) 110-129 (borderline high) ≥130 (high) |
| Cholesterol/HDL | 2.1 | 2.9 | <3.5 |
| . | Week 0 . | Week 4 . | Reference Range . |
|---|---|---|---|
| White blood cell count, 1000 cells/μL | 18.7a | 14.9a | 4.85-9.69 |
| Hemoglobin, g/dL | 13.1 | 13.2 | 11.4-14.7 |
| ESR, mm/h | 55a | 9 | 0-30 |
| ALT, units/L | 46a | 49a | 3-30 |
| Albumin, g/dL | 4.3 | 4.6 | 3.0-4.6 |
| CRP, mg/dL | 2.28a | <0.06 | ≤0.50 |
| Cholesterol, fasting | 171a | 182a | <170 (acceptable) 170-199 (borderline high) ≥200 (high) |
| Triglycerides, fasting | 97a | 55 | <90 (acceptable) 90-129 (borderline high) ≥130 (high) |
| HDL, fasting | 80.5 | 63.6 | <40—low 40-45—borderline ≥45 (acceptable) |
| Non-HDL cholesterol | 90 | 118 | <120 (acceptable) 120-144 (borderline high) ≥145 (high) |
| LDL, fasting | 71 | 107 | <110 (acceptable) 110-129 (borderline high) ≥130 (high) |
| Cholesterol/HDL | 2.1 | 2.9 | <3.5 |
aIndicates values outside of reference range.
Abbreviations: ALT, alanine transaminase; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
| . | Week 0 . | Week 4 . | Reference Range . |
|---|---|---|---|
| White blood cell count, 1000 cells/μL | 18.7a | 14.9a | 4.85-9.69 |
| Hemoglobin, g/dL | 13.1 | 13.2 | 11.4-14.7 |
| ESR, mm/h | 55a | 9 | 0-30 |
| ALT, units/L | 46a | 49a | 3-30 |
| Albumin, g/dL | 4.3 | 4.6 | 3.0-4.6 |
| CRP, mg/dL | 2.28a | <0.06 | ≤0.50 |
| Cholesterol, fasting | 171a | 182a | <170 (acceptable) 170-199 (borderline high) ≥200 (high) |
| Triglycerides, fasting | 97a | 55 | <90 (acceptable) 90-129 (borderline high) ≥130 (high) |
| HDL, fasting | 80.5 | 63.6 | <40—low 40-45—borderline ≥45 (acceptable) |
| Non-HDL cholesterol | 90 | 118 | <120 (acceptable) 120-144 (borderline high) ≥145 (high) |
| LDL, fasting | 71 | 107 | <110 (acceptable) 110-129 (borderline high) ≥130 (high) |
| Cholesterol/HDL | 2.1 | 2.9 | <3.5 |
| . | Week 0 . | Week 4 . | Reference Range . |
|---|---|---|---|
| White blood cell count, 1000 cells/μL | 18.7a | 14.9a | 4.85-9.69 |
| Hemoglobin, g/dL | 13.1 | 13.2 | 11.4-14.7 |
| ESR, mm/h | 55a | 9 | 0-30 |
| ALT, units/L | 46a | 49a | 3-30 |
| Albumin, g/dL | 4.3 | 4.6 | 3.0-4.6 |
| CRP, mg/dL | 2.28a | <0.06 | ≤0.50 |
| Cholesterol, fasting | 171a | 182a | <170 (acceptable) 170-199 (borderline high) ≥200 (high) |
| Triglycerides, fasting | 97a | 55 | <90 (acceptable) 90-129 (borderline high) ≥130 (high) |
| HDL, fasting | 80.5 | 63.6 | <40—low 40-45—borderline ≥45 (acceptable) |
| Non-HDL cholesterol | 90 | 118 | <120 (acceptable) 120-144 (borderline high) ≥145 (high) |
| LDL, fasting | 71 | 107 | <110 (acceptable) 110-129 (borderline high) ≥130 (high) |
| Cholesterol/HDL | 2.1 | 2.9 | <3.5 |
aIndicates values outside of reference range.
Abbreviations: ALT, alanine transaminase; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Discussion
To the author’s knowledge, this is the first report to highlight the successful use of upadacitinib in pediatric inflammatory bowel disease (IBD). There is an urgent need for expansion of available therapies for pediatric IBD. Multiple studies have found higher and earlier biologic use in pediatric compared to adult-onset IBD,1,2 yet despite this, anti-TNF therapy remains the only biologic or small-molecule therapy approved by the Food and Drug Administration for use in patients <18 years of age. Clinicians caring for patients with disease refractory to anti-TNF therapy must resort to off-label treatment, which poses challenges including insurance denials, delays in treatment, and lack of clarity around dosing and safety. Clinical trials of upadacitinib in adult ulcerative colitis and Crohn’s disease have demonstrated promising results.3-6 Inclusion of pediatric patients in IBD clinical trials is essential to advancing quality care for this vulnerable population.
Funding
L.V.C. is supported by a Crohn’s and Colitis Foundation Research Fellows Award (Award Number 830997).
Conflict of Interest
None declared.
