Ustekinumab for the Treatment of Anti-TNF-resistant Crohnʼs Disease: The McGill Experience
Bibliographic record
Abstract
Purpose: Ustekinumab is a fully human IgG1κ monoclonalantibody that blocks the biologic activity of interleukin-12/23 through their common p40 subunit. Ustekinumab has been approved for treatment of plaque psoriasis. It was demonstrated to be effective for induction and maintenance of clinical response in anti-TNF resistant Crohn's disease (CD). The aim of this study was to analyse a real-life experience with open-label use of ustekinumab in anti-TNF=resistant CD patients in a tertiary referral center setting. Methods: This was a retrospective observational study. Clinical response was defined by physician's global assessment combined with decision to continue therapy. Patients were followed for up to 12 (8.6± 6) months or until discontinuation of ustekinumab. Sixteen (88.9%) patients received a loading dose ranging from 45 mg at week 0 and 4-90 mg at weeks 0,1, and 2. Initial maintenance doses included: 90 mg q8 weeks - 11 (61.1%), 90 mg q4 weeks -4 (22.2%), 45 mg q12 weeks-2 (12.5%), and 90 mg q12- in 1 (6.2%) patient. The primary endpoint was clinical response by week 12. Results: Patient characteristics: 18 patients treated at the McGill University IBD Centers (February, 2011-December, 2012) were included. The demographic and clinical characteristics of the patients were as follows: male-50%, age-32.9 ±13.8 years, age of onset of disease - 20.3 ±12.6 years. The disease characteristics were as following: location- ileocolonic-72.3%, colonic - 27.7, perianal disease - 27.7%, disease phenotype - luminal -44.4%, penetrating -38.9%, stricturing - 16.7%. Five (27.7%) patients had undergone total colectomy and ileostomy prior to initiation of ustekinumab. Previous therapies included a thiopurine drug in 100%, infliximab-in 100%, adalimumab-in 87.5%, certolizumab- in 25%, and methotrexate in 77.2% of the patients. Eleven (61.1%) patients were steroid-dependent at the time of initiation of ustekinumab. Treatment outcomes: Clinical response by 12 weeks was achieved in 11 (61.1%) patients. Six (54.5%) of these patients were steroid-dependent at treatment onset, three (50%) were able to discontinue steroids, and three (50%) decreased their prednisone dose by 50%. One additional patient achieved a clinical response after 16 weeks. Eight patients with short-term response were followed for 6 months, and six (75%) maintained their response. Five (83.3%) patients with maintained clinical response at six months were steroid-free. Four (66.7%) patients were followed for 12 months, and all were still clinically responsive and steroid-free. Conclusion: In this cohort of severe anti-TNF resistant CD patients, initial response to subcutaneous ustekinumab resulted in clinical response in 61.1% of patients, with the majority of responders sustaining the benefit for 6-12 months.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".