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These two randomized trials should increase confidence in SC infliximab as a convenient alternative to intravenous delivery, reported co–lead authors Stephen B. Hanauer, MD, AGAF, of Northwestern Feinberg School of Medicine, Chicago, Illinois, and Bruce E. Sands, MD, AGAF, of Icahn School of Medicine at Mount Sinai, New York City, and colleagues.
Specifically, the trials evaluated CT-P13, an infliximab biosimilar, which was Food and Drug Administration approved for intravenous (IV) use in 2016. The SC formulation was approved in the United States in 2023 as a new drug, requiring phase 3 efficacy confirmatory trials.
“Physicians and patients may prefer SC to IV treatment for IBD, owing to the convenience and flexibility of at-home self-administration, a different exposure profile with high steady-state levels, reduced exposure to nosocomial infection, and health care system resource benefits,” the investigators wrote in Gastroenterology.
One trial included patients with Crohn’s disease (CD), while the other enrolled patients with ulcerative colitis (UC). Eligibility depended upon inadequate responses or intolerance to corticosteroids and immunomodulators.
All participants began by receiving open-label IV CT-P13, at a dosage of 5 mg/kg, at weeks 0, 2, and 6. At week 10, those who responded to the IV induction therapy were randomized in a 2:1 ratio to continue with either the SC formulation of CT-P13 (120 mg) or switch to placebo, administered every 2 weeks until week 54.
The CD study randomized 343 patients, while the UC study had a larger cohort, with 438 randomized. Median age of participants was in the mid-30s to late 30s, with a majority being White and male. Baseline disease severity, assessed by the Crohn’s Disease Activity Index (CDAI) for CD and the modified Mayo score for UC, was similar across treatment groups.
The primary efficacy endpoint was clinical remission at week 54, defined as a CDAI score of less than 150 for CD and a modified Mayo score of 0-1 for UC.
In the CD study, 62.3% of patients receiving CT-P13 SC achieved clinical remission, compared with 32.1% in the placebo group, with a treatment difference of 32.1% (95% CI, 20.9-42.1; P < .0001). In addition, 51.1% of CT-P13 SC-treated patients achieved endoscopic response, compared with 17.9% in the placebo group, yielding a treatment difference of 34.6% (95% CI, 24.1-43.5; P < .0001).
In the UC study, 43.2% of patients on CT-P13 SC achieved clinical remission at week 54, compared with 20.8% of those on placebo, with a treatment difference of 21.1% (95% CI, 11.8-29.3; P < .0001). Key secondary endpoints, including endoscopic-histologic mucosal improvement, also favored CT-P13 SC over placebo with statistically significant differences.
The safety profile of CT-P13 SC was comparable with that of IV infliximab, with no new safety concerns emerging during the trials.
“Our results demonstrate the superior efficacy of CT-P13 SC over placebo for maintenance therapy in patients with moderately to severely active CD or UC after induction with CT-P13 IV,” the investigators wrote. “Importantly, the findings confirm that CT-P13 SC is well tolerated in this population, with no clinically meaningful differences in safety profile, compared with placebo. Overall, the results support CT-P13 SC as a treatment option for maintenance therapy in patients with IBD.”
The LIBERTY studies were funded by Celltrion. The investigators disclosed relationships with Pfizer, Gilead, Takeda, and others.
Intravenous (IV) infliximab-dyyb, also called CT-P13 in clinical trials, is a biosimilar that was approved in the United States in 2016 under the brand name Inflectra. It received approval in Europe and elsewhere under the brand name Remsima.
The study from Hanauer and colleagues represents a milestone in biosimilar development as the authors studied an injectable form of the approved IV biosimilar, infliximab-dyyb. How might efficacy compare amongst the two formulations? The LIBERTY studies did not include an active IV infliximab comparator to answer this question. Based on a phase 1, open label trial, subcutaneous (SC) infliximab appears noninferior to IV infliximab.
It is remarkable that we have progressed from creating highly similar copies of older biologics whose patents have expired, to reimagining and modifying biosimilars to potentially improve on efficacy, dosing, tolerability, or as in the case of SC infliximab-dyyb, providing a new mode of delivery. For SC infliximab, whether the innovator designation will cause different patterns of use based on cost or other factors, compared with places where the injectable and intravenous formulations are both considered biosimilars, remains to be seen.
Fernando S. Velayos, MD, MPH, AGAF, is director of the Inflammatory Bowel Disease Program, The Permanente Group Northern California; adjunct investigator at the Kaiser Permanente Division of Research; and chief of Gastroenterology and Hepatology, Kaiser Permanente San Francisco Medical Center. He reported no conflicts of interest.
Intravenous (IV) infliximab-dyyb, also called CT-P13 in clinical trials, is a biosimilar that was approved in the United States in 2016 under the brand name Inflectra. It received approval in Europe and elsewhere under the brand name Remsima.
The study from Hanauer and colleagues represents a milestone in biosimilar development as the authors studied an injectable form of the approved IV biosimilar, infliximab-dyyb. How might efficacy compare amongst the two formulations? The LIBERTY studies did not include an active IV infliximab comparator to answer this question. Based on a phase 1, open label trial, subcutaneous (SC) infliximab appears noninferior to IV infliximab.
It is remarkable that we have progressed from creating highly similar copies of older biologics whose patents have expired, to reimagining and modifying biosimilars to potentially improve on efficacy, dosing, tolerability, or as in the case of SC infliximab-dyyb, providing a new mode of delivery. For SC infliximab, whether the innovator designation will cause different patterns of use based on cost or other factors, compared with places where the injectable and intravenous formulations are both considered biosimilars, remains to be seen.
Fernando S. Velayos, MD, MPH, AGAF, is director of the Inflammatory Bowel Disease Program, The Permanente Group Northern California; adjunct investigator at the Kaiser Permanente Division of Research; and chief of Gastroenterology and Hepatology, Kaiser Permanente San Francisco Medical Center. He reported no conflicts of interest.
Intravenous (IV) infliximab-dyyb, also called CT-P13 in clinical trials, is a biosimilar that was approved in the United States in 2016 under the brand name Inflectra. It received approval in Europe and elsewhere under the brand name Remsima.
The study from Hanauer and colleagues represents a milestone in biosimilar development as the authors studied an injectable form of the approved IV biosimilar, infliximab-dyyb. How might efficacy compare amongst the two formulations? The LIBERTY studies did not include an active IV infliximab comparator to answer this question. Based on a phase 1, open label trial, subcutaneous (SC) infliximab appears noninferior to IV infliximab.
It is remarkable that we have progressed from creating highly similar copies of older biologics whose patents have expired, to reimagining and modifying biosimilars to potentially improve on efficacy, dosing, tolerability, or as in the case of SC infliximab-dyyb, providing a new mode of delivery. For SC infliximab, whether the innovator designation will cause different patterns of use based on cost or other factors, compared with places where the injectable and intravenous formulations are both considered biosimilars, remains to be seen.
Fernando S. Velayos, MD, MPH, AGAF, is director of the Inflammatory Bowel Disease Program, The Permanente Group Northern California; adjunct investigator at the Kaiser Permanente Division of Research; and chief of Gastroenterology and Hepatology, Kaiser Permanente San Francisco Medical Center. He reported no conflicts of interest.
These two randomized trials should increase confidence in SC infliximab as a convenient alternative to intravenous delivery, reported co–lead authors Stephen B. Hanauer, MD, AGAF, of Northwestern Feinberg School of Medicine, Chicago, Illinois, and Bruce E. Sands, MD, AGAF, of Icahn School of Medicine at Mount Sinai, New York City, and colleagues.
Specifically, the trials evaluated CT-P13, an infliximab biosimilar, which was Food and Drug Administration approved for intravenous (IV) use in 2016. The SC formulation was approved in the United States in 2023 as a new drug, requiring phase 3 efficacy confirmatory trials.
“Physicians and patients may prefer SC to IV treatment for IBD, owing to the convenience and flexibility of at-home self-administration, a different exposure profile with high steady-state levels, reduced exposure to nosocomial infection, and health care system resource benefits,” the investigators wrote in Gastroenterology.
One trial included patients with Crohn’s disease (CD), while the other enrolled patients with ulcerative colitis (UC). Eligibility depended upon inadequate responses or intolerance to corticosteroids and immunomodulators.
All participants began by receiving open-label IV CT-P13, at a dosage of 5 mg/kg, at weeks 0, 2, and 6. At week 10, those who responded to the IV induction therapy were randomized in a 2:1 ratio to continue with either the SC formulation of CT-P13 (120 mg) or switch to placebo, administered every 2 weeks until week 54.
The CD study randomized 343 patients, while the UC study had a larger cohort, with 438 randomized. Median age of participants was in the mid-30s to late 30s, with a majority being White and male. Baseline disease severity, assessed by the Crohn’s Disease Activity Index (CDAI) for CD and the modified Mayo score for UC, was similar across treatment groups.
The primary efficacy endpoint was clinical remission at week 54, defined as a CDAI score of less than 150 for CD and a modified Mayo score of 0-1 for UC.
In the CD study, 62.3% of patients receiving CT-P13 SC achieved clinical remission, compared with 32.1% in the placebo group, with a treatment difference of 32.1% (95% CI, 20.9-42.1; P < .0001). In addition, 51.1% of CT-P13 SC-treated patients achieved endoscopic response, compared with 17.9% in the placebo group, yielding a treatment difference of 34.6% (95% CI, 24.1-43.5; P < .0001).
In the UC study, 43.2% of patients on CT-P13 SC achieved clinical remission at week 54, compared with 20.8% of those on placebo, with a treatment difference of 21.1% (95% CI, 11.8-29.3; P < .0001). Key secondary endpoints, including endoscopic-histologic mucosal improvement, also favored CT-P13 SC over placebo with statistically significant differences.
The safety profile of CT-P13 SC was comparable with that of IV infliximab, with no new safety concerns emerging during the trials.
“Our results demonstrate the superior efficacy of CT-P13 SC over placebo for maintenance therapy in patients with moderately to severely active CD or UC after induction with CT-P13 IV,” the investigators wrote. “Importantly, the findings confirm that CT-P13 SC is well tolerated in this population, with no clinically meaningful differences in safety profile, compared with placebo. Overall, the results support CT-P13 SC as a treatment option for maintenance therapy in patients with IBD.”
The LIBERTY studies were funded by Celltrion. The investigators disclosed relationships with Pfizer, Gilead, Takeda, and others.
These two randomized trials should increase confidence in SC infliximab as a convenient alternative to intravenous delivery, reported co–lead authors Stephen B. Hanauer, MD, AGAF, of Northwestern Feinberg School of Medicine, Chicago, Illinois, and Bruce E. Sands, MD, AGAF, of Icahn School of Medicine at Mount Sinai, New York City, and colleagues.
Specifically, the trials evaluated CT-P13, an infliximab biosimilar, which was Food and Drug Administration approved for intravenous (IV) use in 2016. The SC formulation was approved in the United States in 2023 as a new drug, requiring phase 3 efficacy confirmatory trials.
“Physicians and patients may prefer SC to IV treatment for IBD, owing to the convenience and flexibility of at-home self-administration, a different exposure profile with high steady-state levels, reduced exposure to nosocomial infection, and health care system resource benefits,” the investigators wrote in Gastroenterology.
One trial included patients with Crohn’s disease (CD), while the other enrolled patients with ulcerative colitis (UC). Eligibility depended upon inadequate responses or intolerance to corticosteroids and immunomodulators.
All participants began by receiving open-label IV CT-P13, at a dosage of 5 mg/kg, at weeks 0, 2, and 6. At week 10, those who responded to the IV induction therapy were randomized in a 2:1 ratio to continue with either the SC formulation of CT-P13 (120 mg) or switch to placebo, administered every 2 weeks until week 54.
The CD study randomized 343 patients, while the UC study had a larger cohort, with 438 randomized. Median age of participants was in the mid-30s to late 30s, with a majority being White and male. Baseline disease severity, assessed by the Crohn’s Disease Activity Index (CDAI) for CD and the modified Mayo score for UC, was similar across treatment groups.
The primary efficacy endpoint was clinical remission at week 54, defined as a CDAI score of less than 150 for CD and a modified Mayo score of 0-1 for UC.
In the CD study, 62.3% of patients receiving CT-P13 SC achieved clinical remission, compared with 32.1% in the placebo group, with a treatment difference of 32.1% (95% CI, 20.9-42.1; P < .0001). In addition, 51.1% of CT-P13 SC-treated patients achieved endoscopic response, compared with 17.9% in the placebo group, yielding a treatment difference of 34.6% (95% CI, 24.1-43.5; P < .0001).
In the UC study, 43.2% of patients on CT-P13 SC achieved clinical remission at week 54, compared with 20.8% of those on placebo, with a treatment difference of 21.1% (95% CI, 11.8-29.3; P < .0001). Key secondary endpoints, including endoscopic-histologic mucosal improvement, also favored CT-P13 SC over placebo with statistically significant differences.
The safety profile of CT-P13 SC was comparable with that of IV infliximab, with no new safety concerns emerging during the trials.
“Our results demonstrate the superior efficacy of CT-P13 SC over placebo for maintenance therapy in patients with moderately to severely active CD or UC after induction with CT-P13 IV,” the investigators wrote. “Importantly, the findings confirm that CT-P13 SC is well tolerated in this population, with no clinically meaningful differences in safety profile, compared with placebo. Overall, the results support CT-P13 SC as a treatment option for maintenance therapy in patients with IBD.”
The LIBERTY studies were funded by Celltrion. The investigators disclosed relationships with Pfizer, Gilead, Takeda, and others.
FROM GASTROENTEROLOGY