Tolerability of Ustekinumab in Induction and Maintenance for the Treatment of Crohnʼs Disease
Bibliographic record
Abstract
Introduction: Tolerance to therapy is critical for patients to receive the maximal treatment benefit. In Phase 3 clinical trials for ustekinumab (UST) for moderate to severe Crohn's disease (CD), UNITI-1 enrolled anti-TNF failures and UNITI-2 enrolled conventional therapy failures. In UNITI-1, 36.4% had previous intolerance (infusion-related reactions [IRR], delayed hypersensitivity reactions, or injection site reactions [ISR]) that led to discontinuation of the anti-TNF. UNITI-2 enrolled patients that were not intolerant to anti-TNFs, but some were intolerant to immunomodulators (39%) or corticosteroids (15%). Here we assess tolerability as measured by IRR, delayed hypersensitivity, or ISR to UST in the Phase 3 CD trials. Methods: All enrolled patients in UNITI-1 and UNITI-2 were given an intravenous (IV) induction infusion of UST 130mg, UST ˜6 mg/kg, or placebo (PBO). The IM-UNITI maintenance study began 8 weeks after IV induction; UST IV responders were randomized to UST 90mg SQ Q8W, UST 90mg Q12W, or PBO. Non-randomized patients could receive 130mg IV UST, then continued to SC PBO, UST 90mg Q8W, UST 90mg Q12W maintenance therapy, or discontinued. Results: Overall, IRR were infrequent: 4.0 % and 1.9 % of all patients in UNITI 1 & 2, respectively, experienced infusion reactions to the single IV dose. There were no differences in IRR between PBO & UST, or between UST doses (Table 1). During IM-UNITI, IRR to PBO and UST 130mg were similar and infrequent (Table 1). There were no anaphylactic or delayed hypersensitivity reactions to any IV dose. ISRs were infrequent and not different across groups (Table 2). In the combined (randomized and non- randomized) population, ISRs were 1.7 % with PBO, and 3.0% with UST. No serious ISRs were reported. The most common ISR was erythema, reported in 1.1 % of PBO, and 1.7% of UST. There were no anaphylactic or delayed hypersensitivity reactions to any SC dose. Amongst randomized patients, ISRs were infrequent and consistent between groups. ISRs occurred in 3/418 (0.7 %) of all UST 90mg Q12W injections and in 12/599 (2.0 %) of all UST 90mg Q8W injections. One patient in the entire phase 3 program discontinued therapy due to ISR.Table: Table. Infusion-related reactions*Table: Table. Injection site reactionsConclusion: In a broad population of patients with Crohn's disease, many of whom were intolerant to previous therapies, UST had a tolerable profile. Rates of IRR and ISR were minimal, and were not obviously different between groups, nor populations.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".