Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY).

BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. (Co-) primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).

Ustekinumab in paediatric patients with moderately to severely active Crohn's disease: UniStar study long-term extension results.

OBJECTIVES: To assess the efficacy, safety, immunogenicity, and pharmacokinetics through 240 weeks of ustekinumab treatment in paediatric patients from the long-term extension (LTE) of the phase 1, double-blind UniStar trial. METHODS: Paediatric patients with moderately to severely active Crohn's disease (CD) were randomised 1:1 and stratified by body weight (<40 or ≥40 kg) to low- or high-dose intravenous ustekinumab followed by a subcutaneous maintenance dose at Week 8. At Week 16, patients were eligible to enter the LTE at the discretion of the investigator and continued maintenance dosing every 8 weeks up to Week 240. RESULTS: Of the 34 patients who entered the LTE, 25 patients with evaluable data completed Week 48, and 41.2% (14/34) achieved clinical remission at Week 48. Among the 24 patients with Week-0 C-reactive protein (CRP) levels ≥3 mg/L, 29.2% (7/24) achieved normalisation of CRP at Week 48, while imputing missing data as failures. Through Week 240, the most common adverse events were infections (n = 28) and gastrointestinal disorders (n = 26). The most common serious adverse event was worsening of CD (n = 6). Only one patient had detectable antibodies to ustekinumab. Median serum ustekinumab concentrations remained consistent through Week 48, were detectable through Week 224, and trended lower in patients <40 kg. CONCLUSIONS: Efficacy and pharmacokinetics through 1 year and safety and immunogenicity through 4 years of ustekinumab treatment in paediatric patients with CD were generally comparable to those previously reported in adults.

Combination biologic therapy in pediatric inflammatory bowel disease: Safety and efficacy over a minimum 12-month follow-up period.

OBJECTIVES: The severe course of inflammatory bowel diseases (IBDs) refractory to advanced therapies in children results in the search for new therapeutic methods. The aim of this study was to evaluate the efficacy and safety of dual therapy with biologics in a cohort of children with IBD. METHODS: Retrospective analysis of data from 29 children with a diagnosis of IBD, 19 with ulcerative colitis (66%), 10 with Crohn's disease (CD) (34%) qualified for dual biological therapy (DBT). The median age of patients was five (interquartile range [IQR], 1-15) years at diagnosis of IBD and 14 (IQR, 3-17) years at eligibility for dual therapy. Thirteen (45%) patients were treated with vedolizumab/adalimumab (VDZ + ADA), 13 (45%) with ustekinumab/adalimumab (UST + ADA), three (10%) with infliximab/vedolizumab (IFX + VDZ). RESULTS: Clinical remission was achieved in 13 (45%; seven UC and six CD) and 12 (41%; seven UC and five CD) Pediatric Weighted Crohn's Disease Activity Index (wPCDAI)/Pediatric Ulcerative Colitis Activity Index (PUCAI) patients after 4 and 12 months at the initiation of dual therapy. Clinical response based on wPCDAI/PUCAI was reported in 16 (55%; nine UC and seven CD) and 12 (41% seven UC and five CD) children after 4 and 12 months of follow-up, respectively. The median fecal calprotectin decreased significantly from 1240 µg/g (53-10,100) to 160 µg/g (5-2500; p = 0.004) between baseline and Month 4 and from 749 at baseline (57-10,100) to 17 (5-3110; p = 0.12) over 12 months. Moreover, 34% (six UC and four CD) of patients achieved endoscopic remission. CONCLUSIONS: DBT seems to be an effective alternative therapeutic option for patients with moderate and severe IBD.