P0608 Safety of guselkumab in Inflammatory Bowel Disease up to 1 year: Integrated safety analysis of phase 2 and 3 studies in Crohn’s Disease and Ulcerative Colitis
Bibliographic record
Abstract
Abstract Background Guselkumab (GUS), a dual-acting IL-23 inhibitor that potently neutralizes IL-23 and binds to CD64 (a receptor on cells that produce IL-23), is currently approved in the United States for treatment of ulcerative colitis (UC) and worldwide for the treatment of plaque psoriasis and psoriatic arthritis. While GUS has been shown to be safe in Crohn’s disease (CD) and UC, safety results have only been reported in individual trials to date. To characterize the overall safety profile of GUS in inflammatory bowel disease (IBD), we evaluated pooled safety data from Phase 2/3 clinical trials of GUS in CD and UC. Methods Participants (pts) with moderately to severely active CD (n=1492; GALAXI 1, 2, and 3, and GRAVITI) or UC (n=1514; QUASAR Induction Study 1, Induction Study 2, and Maintenance Study and VEGA-GUS monotherapy arm only) were assigned to GUS 200 mg intravenous (IV) or 400 mg subcutaneous (SC) induction (GRAVITI only) at Weeks 0, 4, and 8, followed by GUS 100 mg SC every 8 weeks or 200 mg SC every 4 weeks; or placebo (PBO). SC maintenance treatment continued through approximately 1 year. GUS studies were pooled for the induction period (GALAXI, GRAVITI, and QUASAR; IV and SC, Weeks 0-12 [VEGA excluded due to no PBO control]) and through 1 year (GALAXI, GRAVITI, QUASAR, and VEGA). In this pooled analysis, safety events were normalized to 100 pt-years (PY) of follow-up with corresponding confidence intervals. Results Through Week 12, 1703 pts were treated with GUS with 399.9 PY of follow-up. Rates of adverse events (AEs) were similar between pts treated with GUS (200 mg IV or 400 mg SC) and PBO (Figure 1A). AEs occurred at a rate of 202.82/100 PYs and 223.26/100 PY, serious AEs at 11.75/100 PY and 28.56/100 PY, AEs leading to study agent discontinuation at 5.50/100 PY and 16.32/100 PY, and serious infections at 1.50/100 PY and 1.17/100 PY, for GUS and PBO, respectively. Through 1 year, 2057 pts were treated with GUS, with 1752.1 PY of follow-up. Rates of AEs, SAEs, AEs leading to discontinuation, and serious infections, were no higher in GUS-treated than PBO-treated pts (Figure 1B). Through 1 year, no anaphylactic or serum sickness reactions were reported, and rates of malignancy, opportunistic infection, major adverse cardiovascular events, and clinically important hepatic disorders were low (Table 1). In GUS-treated pts, one pt (from an endemic region) reported active tuberculosis, and 2 deaths (acute myocardial infarction in a pt with pre-existing cardiovascular risk factors and non-suicidal gunshot wound, respectively) occurred. Conclusion Through 1 year of treatment, GUS demonstrated a favorable safety profile comparable to placebo in patients with CD and UC. No new safety concerns were identified.
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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 | 0.031 | 0.018 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.007 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".