A134 ANTI-IL-12/23P40 ANTIBODIES FOR MAINTENANCE OF REMISSION IN CROHN’S DISEASE
Bibliographic record
Abstract
Ustekinumab (CNTO 1275) is a monoclonal antibody that targets the standard p40 subunit of cytokines interleukin-12 and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of Crohn’s disease. To assess the efficacy and safety of anti-IL-12/23p40 antibodies for maintenance of remission in Crohn’s disease. A comprehensive search of MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, and The Cochrane IBD Group Specialized Register through September 2016 was completed. Randomized controlled trials (RCTs) in which monoclonal antibodies against IL-12/23p40 were compared to placebo or another active comparator in adult patients with active Crohn’s disease were identified for inclusion. Two RCTs (n=542) met the inclusion criteria. However, the two studies were not pooled due to differences in time points for analysis. One study (n=145) compared doses of 1, 3, and 6 mg/kg of ustekinumab to placebo for 22 weeks. There was no statistically significant difference in remission rates in this study (RR=0.80, 95% CI 0.63 to 1.02, low-quality evidence). However, ustekinumab was statistically superior to placebo in rates of clinical response (RR=0.53, 95% CI 0.36 to 0.79, low-quality evidence). The other included study (n=259) compared doses of 90 mg of ustekinumab administered every 8 weeks and every 12 weeks to placebo for 44 weeks. Ustekinumab was shown superior to placebo in maintenance of remission in both 90 mg every 8 weeks and every 12 weeks (RR= 0.73, 95% CI 0.58 to 0.92, moderate-quality evidence and RR=0.80, 95% CI 0.65 to 0.99, moderate quality evidence respectively). Ustekinumab was also shown to be superior to placebo with respect to clinical response in the 8 and 12 week dosing groups (RR=0.73, 95% CI 0.56 to 0.94, low-quality evidence and RR=0.75, 95% CI 0.58 to 0.97, low-quality evidence respectively). Data on adverse effects was pooled from both studies and showed there was no statistically significant differences in incidence of adverse events (AE) or serious adverse events (SAE) (RR=0.94, 95% CI 0.86–1.03, low quality of evidence and RR=0.69, 95% CI 0.42 to 1.15 respectively). Low to moderate quality evidence suggests that ustekinumab is effective for maintenance of clinical response when administered for 22 and 44 weeks and maintenance of clinical remission when administered for 44 weeks. Ustekinumab appears to be safe with no increased risk of AE’s, SAE’s or withdrawal due to AE’s. Further studies are required to increase the quality of evidence available for the use of ustekinumab in the maintenance of moderate to severe Crohn’s disease. Cochrane IBD Group and Summer Opportunities Research Program, Schulich School of Medicine and Dentistry
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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 | 0.006 | 0.017 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.008 |
| Bibliometrics | 0.004 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.012 | 0.001 |
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".