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Are Subcutaneous Drugs as Safe and Effective for IBD as Intravenous Drugs?

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The infliximab biosimilar CT-P13 subcutaneous (SC) is non-inferior to CT-P13 intravenous (IV) in pharmacokinetics, efficacy, safety, and immunogenicity outcomes of patients with inflammatory bowel diseases (IBD), researchers report in the June issue of Gastroenterology. These findings support the CT-P13 SC formulation as a suitable therapeutic agent to expand and improve treatment options for patients with IBD.

Proportion of patients with ulcerative colitis who achieved clinical remission after receiving CT-P13 SC or IV, based on partial Mayo score.

Guidelines recommend tumor necrosis factor (TNF) inhibitors, including infliximab, for treatment of patients with moderate–severe ulcerative colitis or Crohn’s disease that have not responded to conventional therapy. Infliximab biosimilars, such as CT-P13, have been developed and are increasing used for treatment of IBD.

CT-P13 administered in an IV formulation (CT-P13 IV) has an established safety and efficacy profile in the treatment of IBD, and a subcutaneous (SC) CT-P13 formulation has been developed, which might allow for self-administration. IV-administered biologics enter the circulation, resulting in immediate drug exposure and high initial peak concentrations, compared with the slow absorption, incomplete bioavailability, and lower peak concentrations of SC-administered biologics. However, SC biologics can be administered at home, helping patients avoid medical visits and associated travel, and benefit health care systems by optimizing resources and reducing costs.
 performed an open-label, randomized, controlled trial to evaluate CT-P13 SC maintenance in patients with active Crohn’s disease or ulcerative colitis. This phase 1 study enrolled patients with active ulcerative colitis (total Mayo score 6–12 points with endoscopic subscore ≥2) or Crohn’s disease (Crohn’s Disease Activity Index 220–450 points), naive to TNF inhibitors, at 50 centers. After CT-P13 IV induction at weeks 0 and 2, patients were randomly assigned to groups given CT-P13 SC (n=66) every 2 weeks, from week 6 to week 54, or CT-P13 IV (n=65) every 8 weeks, from week 6 to week 22. At week 30, all patients receiving CT-P13 IV switched to CT-P13 SC week 54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at week 22 (Ctrough,W22), determined if the lower bound of the 2-sided 90% CI for the ratio of geometric least-squares means exceeded 80%.

Infliximab trough levels in patients given CT-P13 SC were consistently maintained above the target concentration throughout the study, independently of whether patients received CT-P13 SC directly after dose loading or had switched to CT-P13 SC at week 30 to continue maintenance therapy.

Rates of clinical remission at week 30 and week 54 were comparable between SC and IV groups (see Figure), for patients with ulcerative colitis or Crohn’s disease. The proportions of patients with ulcerative colitis who achieved clinical remission (total Mayo score of ≤2 points) and endoscopic remission (absolute Mayo endoscopic subscore of ≤1 point) did not differ significantly between the SC and IV groups at week 22 (clinical remission, 44.7% vs 25.6%; endoscopic remission, 47.4% vs 30.8% of patients; P > .05 for both, in the SC and IV arms, respectively). Similarly, in patients with Crohn’s disease, rates of clinical remission (CD Activity Index score of <150 points) and endoscopic remission (absolute simple endoscopic score for CD of ≤2 points) rates were comparable between the SC and IV groups (clinical remission, 60.7% vs 60%; endoscopic remission, 35.7% vs 14.3%; P > .05).

Other efficacy, safety, and immunogenicity assessments were also comparable between groups. After patients switched from CT-P13 IV to CT-P13 SC, similar proportions in each group reported drug-related adverse events (19.7% vs 18.5 in the SC and IV groups, respectively) and developed antidrug antibodies (47.0% vs 38.5 in the SC and IV groups, respectively).

In an editorial that accompanies the article, write that his study provides evidence for the use of CT-P13 SC in patients with IBD, early after induction and after a switch from IV to SC during the maintenance phase.

Solitano et al write that although some patients may still prefer IV administration for the safety of infusion at the hospital and the reassuring effect of nurse and physician presence, SC administration is mainly chosen for its convenience, time savings, and the possibility of self-injection at home. Changes from IV to SC formulations might result in significant economic advantages for hospitals and patients.

The editorial explains that all monoclonal antibodies in the IBD pipeline are launched with SC formulations or IV induction followed by SC maintenance. SC biologics seem to meet the requirements to dismiss their IV formulations: noninferiority, patient preference, and cost savings. Studies are needed to determine whether all indications of IV biologics could be extrapolated or the same optimization strategies could be applied to SC formulations.

 

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Kristine Novak

Kristine Novak

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About The Author:

Dr. Kristine Novak

Dr. Kristine Novak

Dr. Kristine Novak is a science writer and editor based in San Francisco. She has extensive experience covering gastroenterology, hepatology, immunology, oncology, clinical, and biotechnology research discoveries.

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