Subcutaneous infliximab (Zymfentra) remains effective for treating moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC) for up to two years, irrespective of whether it's used alone or with immunosuppressants. Data presented at the American College of Gastroenterology (ACG) 2024 Scientific Sessions in Philadelphia showed that the TNF inhibitor infliximab achieved similar remission rates and safety profiles in both monotherapy and combination therapy regimens for patients with inflammatory bowel syndrome (IBS).
The post hoc analysis of the LIBERTY-CD and LIBERTY-UC trials, led by Bruce E. Sands, MD, from the Icahn School of Medicine at Mount Sinai, compared outcomes based on immunosuppressant use at baseline. The FDA approved subcutaneous infliximab for UC and CD in October 2023 based on these trials.
Key Findings from LIBERTY Trials
In the LIBERTY-UC trial, patients receiving infliximab were more than twice as likely to achieve clinical remission at week 54 compared to the control arm (43.2% vs 20.8%; P < .0001). Similarly, in LIBERTY-CD, the clinical remission rate was significantly higher in the infliximab arm versus the control arm at week 54 (62.3% vs 32.1%; P < .0001).
The analysis included patients with moderate to severely active disease who were randomized to the maintenance infliximab arm from weeks 10 to 54, and those treated in the open-label extension through week 102. The primary endpoints of the pivotal trials were assessed, stratified by patient immunosuppressant use at baseline.
The final analysis included 192 patients with CD and 237 patients with UC, with 126 (65.6%) and 180 (75.9%) receiving infliximab monotherapy versus combination therapy, respectively.
Efficacy Outcomes
Across both LIBERTY-CD and LIBERTY-UC trials, no clinically meaningful differences were observed in clinical remission rates between monotherapy and combination therapy at either the 54-week or 102-week endpoints:
- LIBERTY-CD, 54 weeks: 74.6% monotherapy vs 71.2% combination therapy (P = .1773)
- LIBERTY-CD, 102 weeks: 65.9% vs 59.1%, respectively (P = .0892)
- LIBERTY-UC, 54 weeks: 51.7% vs 56.1%, respectively (P = .5007)
- LIBERTY-UC, 102 weeks: 47.2% vs 38.6%, respectively (P = .215)
Similar insignificant differences were observed in rates of clinical response, corticosteroid-free remission, endoscopic remission or response, and deep remission at both endpoints in both trials. Combination therapy patients generally reported higher mean trough levels of infliximab through week 102 compared to the monotherapy arm.
Safety and Immunogenicity
No meaningful differences in adverse event rates were observed between monotherapy and combination infliximab (80.8% vs 79.5%). However, anti-drug antibody (ADA) positive conversion rates were higher with monotherapy up to weeks 54 and 102.
Clinical Implications
These findings offer clinicians greater confidence in prescribing infliximab for UC or CD, whether initiating treatment with or without immunosuppressants.
According to the research team, "No meaningful differences in efficacy outcomes were observed for patients during maintenance who had a clinical response to infliximab induction either as monotherapy or in combination with immunosuppressants at week 54 and 102. Combination with immunosuppressants resulted in lower formation of ADA with higher drug levels that did not translate to different efficacy outcomes."
