P1142 Time to clinical recapture after dose escalation of subcutaneous infliximab (CT-P13 SC) following loss of response: A post hoc analysis of the 2-year Phase 3 LIBERTY-CD & LIBERTY-UC trials
Authors: Dubinsky M C , Schreiber S , Yarur A J , Sands B E , Hanauer S B , Danese S , Yu H , Kim D H , Lee Y N , Colombel J F 
Published: January 2025

Background

Subcutaneous (SC) infliximab (IFX) is approved for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) at a dose of 120 mg every other week (EOW).1 While the effectiveness of dose escalation (DE) to 240 mg EOW has been suggested,2,3 the time of onset of efficacy following DE represents an important gap in knowledge, especially for patients receiving SC IFX who lose response. This analysis aimed to assess how promptly patients recapture clinical response after DE following loss of response (LoR), and to characterise early recapture after DE.

Methods

This post hoc analysis utilised data from the CT-P13 SC arm in the LIBERTY-CD and LIBERTY-UC trials, where patients received induction therapy with intravenous IFX (5 mg/kg at Weeks [W] 0, W2 and W6) and maintenance therapy with CT-P13 SC (120 mg EOW) from W10.2 DE to 240 mg EOW was allowed after W22. The current analysis included patients who underwent DE following LoR. LoR was defined as a Crohn’s Disease Activity Index (CDAI) increase of ≥100 from W10 with a total score of ≥220 for CD and a modified Mayo score increase of ≥2 and ≥30% increase from W10 with an actual score of ≥5 and an endoscopic subscore of ≥2 for UC. Clinical recapture was defined as a CDAI decrease of ≥100 after LoR and a partial Mayo score (PMS) decrease of ≥2 with a decrease in rectal bleeding (RB) subscore of ≥1, or an absolute RB subscore of 0 or 1 after LoR for CD and UC, respectively. CDAI and PMS were obtained from scheduled (every 8 weeks) and unscheduled visits. Time to clinical recapture was assessed up to W102. Patients who recaptured within 8 weeks after DE were classified as early recapturers, while those who recaptured after 8 weeks were classified as late recapturers. Serum IFX levels were assessed pre-/post-DE.

Results

In the LIBERTY-CD and LIBERTY-UC trials, 20.3% (47/231) and 21.1% (62/294) in the SC arm underwent DE following LoR (Table). Two-thirds of patients recaptured response within 8 weeks (CD: 66.0% [31/47]; UC: 69.4% [43/62]), and over four-fifths of patients recaptured up to W102 (CD: 85.1% [40/47]; UC: 82.3% [51/62]) (Figure). In CD, median serum IFX levels were increased following DE in early (from 8.0 to 22.1 μg/mL) and late recapturers (from 11.1 to 19.8 μg/mL) but not in non-recapturers (from 0.1 to 0.2 μg/mL). In UC, DE resulted in increases in median serum IFX levels in early (from 8.3 to 24.0 μg/mL), late (from 7.4 to 16.5 μg/mL) and non-recapturers (from 8.0 to 22.0 μg/mL).

Conclusion

DE of CT-P13 SC following LoR led to rapid clinical recapture in patients with CD and UC. Serum IFX levels of early recapturers were significantly elevated after DE. Further studies are warranted to investigate other factors related to the rapidity of clinical recapture.

References

1.European Medicines Agency. Available at: https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf. Accessed November 18, 2024.

2.Hanauer SB, et al. Gastroenterology. 2024;167(5):919-933.

3.Danese S, et al. Gastroenterology. 2024;166(3):S13.