Faubion William A, Dubinsky Marla, Ruemmele Frank M, Escher Johanna, Rosh Joel, Hyams Jeffrey S, Eichner Samantha, Li Yao, Reilly Nattanan, Thakkar Roopal B, Robinson Anne M, Lazar Andreas
*Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; †Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York; ‡Pediatric Gastroenterology Unit, Department of Pediatrics, Universite Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, Paris, France; §Department of Pediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands; ‖Pediatric Gastroenterology, Goryeb Children's Hospital/Atlantic Health, Morristown, New Jersey; ¶Division of Digestive Diseases, Connecticut Children's Medical Center, Hartford, Connecticut; **AbbVie Inc., North Chicago, Illinois; and ††AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
Inflamm Bowel Dis. 2017 Mar;23(3):453-460. doi: 10.1097/MIB.0000000000001021.
IMAgINE 1 assessed 52-week efficacy and safety of adalimumab in children with moderate to severe Crohn's disease. Long-term efficacy and safety of adalimumab for patients who entered the IMAgINE 2 extension are reported.
Patients who completed IMAgINE 1 could enroll in IMAgINE 2. Endpoints assessed from weeks 0 to 240 of IMAgINE 2 were Pediatric Crohn's Disease Activity Index remission (Pediatric Crohn's Disease Activity Index ≤ 10) and response (Pediatric Crohn's Disease Activity Index decrease ≥15 from IMAgINE 1 baseline) using observed analysis and hybrid nonresponder imputation (hNRI). For hNRI, discontinued patients were imputed as failures unless they transitioned to commercial adalimumab (with study site closure) or adult care, where last observation was carried forward. Corticosteroid-free remission in patients receiving corticosteroids at IMAgINE 1 baseline, discontinuation of immunomodulators (IMMs) in patients receiving IMMs at IMAgINE 2 baseline, and linear growth improvement were reported as observed. Adverse events were assessed for patients receiving ≥1 adalimumab dose in IMAgINE 1 and 2 through January 2015.
Of 100 patients enrolled in IMAgINE 2, 41% and 48% achieved remission and response (hNRI) at IMAgINE 2 week 240. Remission rates were maintained by 45% (30/67, hNRI) of patients who entered IMAgINE 2 in remission. At IMAgINE 2 week 240, 63% (12/19) of patients receiving corticosteroids at IMAgINE 1 baseline achieved corticosteroid-free remission and 30% (6/20) of patients receiving IMMs at IMAgINE 2 baseline discontinued IMMs. Adalimumab treatment led to growth velocity normalization. No new safety signals were identified.
Efficacy and safety profiles of prolonged adalimumab treatment in children with Crohn's disease were consistent with IMAgINE 1 and adult Crohn's disease adalimumab trials.
IMAgINE 1评估了阿达木单抗治疗中度至重度克罗恩病儿童的52周疗效和安全性。本文报告了进入IMAgINE 2扩展研究的患者使用阿达木单抗的长期疗效和安全性。
完成IMAgINE 1的患者可进入IMAgINE 2。IMAgINE 2第0至240周评估的终点为使用观察性分析和混合无反应者插补法（hNRI）得出的儿童克罗恩病活动指数缓解（儿童克罗恩病活动指数≤10）和反应（儿童克罗恩病活动指数较IMAgINE 1基线下降≥15）。对于hNRI，除非停药患者转为使用商业阿达木单抗（研究点关闭）或成人护理（末次观察数据结转），否则将其视为治疗失败。按观察结果报告在IMAgINE 1基线接受皮质类固醇治疗的患者的无皮质类固醇缓解、在IMAgINE 2基线接受免疫调节剂（IMM）治疗的患者停用IMM以及线性生长改善情况。通过2015年1月评估了IMAgINE 1和2中接受≥1剂阿达木单抗治疗患者的不良事件。
在IMAgINE 2入组的100例患者中，41%和48%在IMAgINE 2第240周达到缓解和反应（hNRI）。进入IMAgINE 2时处于缓解状态的患者中，45%（30/67，hNRI）维持了缓解率。在IMAgINE 2第240周，在IMAgINE 1基线接受皮质类固醇治疗的患者中，63%（12/19）实现了无皮质类固醇缓解，在IMAgINE 2基线接受IMM治疗的患者中，30%（6/20）停用了IMM。阿达木单抗治疗使生长速度恢复正常。未发现新的安全信号。
阿达木单抗长期治疗克罗恩病儿童的疗效和安全性与IMAgINE 1及成人克罗恩病阿达木单抗试验一致。
