Use of Oral Low-dose Cyclophosphamide Therapy in Patients With Refractory Extensive Crohnʼs Disease
Bibliographic record
Abstract
Introduction Cyclophosphamide (CPM) is one of the oldest chemotherapeutic agents available, which also has immunosuppressive properties. It was first used for inflammatory bowel disease (IBD) in 1985, when given to 4 patients who developed pancreatitis on azathioprine. The first case series using pulse IV CPM for steroid-refractory IBD was described in 2003. Case presentation We describe a case of a 23-year-old Caucasian male diagnosed with Crohn's disease (CD) at 14 years of age (Montreal Classification A1L1L4B1p). He was initially treated with infliximab but developed an anaphylactic reaction prompting a transition to adalimumab combined with methotrexate. His disease, however, remained active involving the entire small bowel. He was started on vedolizumab with methotrexate but did not achieve remission. A subsequent transition to ustekinumab allowed tapering off prednisone, but 1 month later, he developed symptoms, which persisted despite dose escalation. A short course of mycophenolate mofetil was attempted but it was unsuccessful.By the end of 2016, he developed arthralgias and osteoporosis, both attributed to steroid use. Given the persistence of inflammation despite conventional medical therapy, he was started on oral CPM (1.5 mg/kg/day), alongside prednisone. At 10 days follow-up, the patient reported significant improvement in his energy levels and abdominal pain. His symptoms continued improving, and he was able to taper prednisone to 15 mg daily at 5 weeks from starting CMP, and achieve clinical remission. Two months into starting therapy, he noted worsening of his symptoms with loose stools, nausea and weight loss. However, CRP (C reactive protein) was trending down. Discontinuation of abaloparatide, which was taken concomitantly, lead to symptom resolution. At his most recent follow-up visit, at 24 weeks from starting CPM, the patient was in clinical remission, on CMP and prednisone 7.5 mg/day. Discussion: The use of oral low-dose CPM offers an improvement in efficacy but also a mild increase in the rate of leukopenia. We chose the oral regimen for its rapid onset, efficacy and steroid-sparing properties, with the convenience of avoiding IV administration. A lower dose was selected to reduce the risk of leukopenia. Besides the 4 cases described in 1985, this is the first description of oral CPM use for induction of remission in a patient with CD. This case highlights another treatment option for highly refractory IBD patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".