Infliximab Improves Ulcerative Colitis, Crohn's Disease Regardless of Immunosuppressants

Subcutaneous infliximab (Zymfentra) remained efficacious for patients with moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC) regardless of combination immunosuppressant therapy through 2 years of treatment, according to new data.¹

Research presented during the late-breaking abstract sessions at the American College of Gastroenterology (ACG) 2024 Scientific Sessions in Philadelphia, PA, this weekend showed the tumor necrosis factor (TNF) inhibitor infliximab is highly efficacious for achieving 1- or 2-year disease remission whether used as a monotherapy or a combination therapy with immunosuppressants in patients with either form of irritable bowel syndrome (IBS). The data further showed consistent safety with either regimen in treated patients, as well.

A post hoc analysis from the LIBERTY-CD and LIBERTY-UC trials, led by Bruce E. Sands, MD, of the Icahn School of Medicine at Mount Sinai, sought to compare the outcomes of infliximab based on immunosuppressant use status at baseline of the phase 3 pivotal trials. Infliximab was approved by the US Food and Drug Administration (FDA) for the treatment of UC and CD in October 2023 on the basis of findings from the 2 trials.²

In LIBERTY-UC, investigators observed that patients randomized to infliximab were more than twice likely to achieve clinical remission than those randomized to the control arm at week 54 (43.2% vs 20.8%; P <.0001). In LIBERTY-CD, the rate of clinical remission was again significantly greater in the infliximab arm versus control at week 54 (62.3% vs 32.1%; P <.0001).

The included patients from the LIBERTY trials were those with moderate to severely active disease randomized to the maintenance infliximab arm from weeks 10 to 54, as well as those who were also treated in the open-label extension through week 102. Sands and colleagues sought the same pivotal trials’ endpoints, stratified by patient immunosuppressant use at baseline.¹

The final analysis included 192 patients with CD and 237 patients with UC; among each arm, 126 (65.6%) and 180 (75.9%) were receiving monotherapy infliximab versus combination with immunosuppressants, respectively.

Across LIBERTY-CD and LIBERTY-UC, investigators observed no clinically meaningful differences in clinical remission between monotherapy infliximab and combination therapy, respectively, at either endpoint of 54 or 102 weeks:

• LIBERTY-CD, 54 weeks: 94 (74.6%) monotherapy vs 47 (71.2%) combination therapy (P = .1773)
• LIBERTY-CD, 102 weeks: 83 (65.9%) vs 39 (59.1%), respectively (P =. 0892)
• LIBERTY-UC, 54 weeks: 93 (51.7%) vs 32 (56.1%), respectively (P = .5007)
• LIBERTY-UC, 102 weeks: 85 (47.2%) vs 22 (38.6%), respectively (P = .215)

The observed similarly insignificant differences in rates of patients to achieve clinical response, corticosteroid-free remission, endoscopic remission or response, or deep remission at either endpoint in either trial. This finding comes despite the fact combination therapy patients generally reported higher mean trough levels of infliximab through week 102 than the monotherapy arm.

Regarding safety, investigators observed no meaningful differences in rates of adverse events with either monotherapy or combination infliximab (80.8% vs 79.5%). The rate of anti-drug antibody (ADA) positive conversion rates were greater with monotherapy up to weeks 54 and 102.

The findings provide prescribing confidence to clinicians treating UC or CD with patients who are initiating infliximab treatment with or without immunosuppressants.

“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,” the team concluded. “Combination with immunosuppressants resulted in lower formation of ADA with higher drug levels that did not translate to different efficacy outcomes.”

References

1. ^{Sands BE, Colombel JF, Hanauer SB, Sandborn WJ, et al. Efficacy, Safety and Immunogenicity of Subcutaneous Infliximab (CT-P13 SC) Monotherapy versus Combination Therapy With Immunosuppressants Post hoc Analysis of LIBERTY-CD and LIBERTY-UC Studies. Abstract presented at: American College of Gastroenterology (ACG) 2024 Scientific Sessions. Philadelphia, PA. October 25 – 30, 2024.}
2. ^{Campbell P. FDA Approves First Subcutaneous Infliximab for Maintenance Therapy in UC and Crohn Disease. HCPLive. Published October 23, 2023. https://www.hcplive.com/view/fda-approves-first-subcutaneous-infliximab-for-maintenance-therapy-in-uc-and-crohn-disease}