A Multicenter Open-Label Study Assessing Pharmacokinetics, Efficacy, And Safety Of Subcutaneous Golimumab In Pediatric Subjects With Moderately-Severely Active Ulcerative Colitis

Pediatric patients with moderate-to-severe ulcerative colitis (UC) who fail 5-aminosalicylates, corticosteroids, and immunomodulators have limited alternative approved treatment options. Golimumab is a subcutaneous (SC) anti-tumor necrosis factor (anti-TNF) agent that has the potential to offer such patients a safe, effective, and convenient treatment option. This is a multicenter open-label study with a pharmacokinetic (PK) portion (week 0-14) and a study extension (weeks 14–126); we report here results through week 14. Subjects aged 2 to 17 years with moderate-to-severe UC (Mayo score 6–12, endoscopy subscore ≥2) who failed previous therapy as noted above and were naive to anti-TNF treatment were enrolled. Subjects received SC golimumab induction at week 0/2 by weight (<45 kg [90/45 mg/m2]; ≥45 kg [200/100 mg]). At week 6, Mayo clinical responders continued golimumab maintenance q4w (<45 kg [45 mg/m2]; ≥45 kg [100 mg]). Key outcome measures included PK and immunogenicity (serum golimumab concentrations, PK parameters, antibodies to golimumab), efficacy (Mayo score, Pediatric Ulcerative Colitis Activity Index (PUCAI) score), and safety (adverse events [AEs], serious AEs, AEs leading to discontinuation). Thirty-five subjects enrolled and received ≥1 dose of golimumab. At baseline, the mean ± SD age, weight, and duration of disease were 13.4 ± 3.2 years (Range 6–17), 51.7 ± 22.7 kg (Range 19.7–134.0) and 2.4 ± 3.1 years (Range 0.2–16.0), respectively. Subjects had moderate-to-severe disease activity (mean ± SD: Mayo score 8.1 ± 1.8 [Range 6–12], PUCAI score 48 ± 17 [Range 15–80], CRP level 10.1 ± 23.9 mg/L [Range 0.1–116.0]). Most (71.4%) had extensive colonic involvement and 85.7% received ≥1 concomitant UC medications at baseline: corticosteroids including budesonide (37.1%), immunomodulators (57.1%), and 5-ASAs (65.7%). At weeks 2, 4, and 6, mean serum golimumab concentrations were 6.5, 6.5, and 2.6 μg/mL, respectively, which were similar to those observed in adults who received 200/100 mg induction. At week 6, 60% and 42.9% of subjects achieved clinical response (Mayo score decrease ≥30% and ≥3 points, rectal bleeding subscore decrease ≥1 or absolute subscore ≤1) and clinical remission (Mayo score ≤2, no individual subscore >1), respectively, and 34.3% achieved PUCAI remission (PUCAI <10). Mucosal healing as evaluated by sigmoidoscopy/colonoscopy at week 6 (Mayo endoscopy subscore ≤1) was achieved in 54.3% of subjects and 22.9% achieved complete healing (Mayo endoscopic subscore 0). Parallel substantial reductions in objective biomarkers of inflammation (CRP, calprotectin, lactoferrin) were observed from baseline to week 6. Among Week 6 Mayo clinical responders who received q4w golimumab maintenance, 57.1% were in PUCAI remission at week 14. Through week 14, 94.3% of subjects reported ≥1 AE and 8.6% had an AE leading to discontinuation. Infections were reported in 37.1% of subjects, none were serious. Injection site reactions were reported in 17.1% of subjects, all were mild. Three subjects were positive for antibodies to golimumab. Eleven subjects (31.4%) reported 13 SAEs, including UC flare (n = 10) and one event each of abdominal pain, iron deficiency anemia, and acute pancreatitis. No opportunistic infections, malignancies or deaths were reported. Golimumab was generally well tolerated in this small open-label study of pediatric subjects with UC. The PK, efficacy, and safety outcomes observed were comparable with those previously reported in the golimumab adult UC phase 3 trials.