DOI: 10.25934/pr00007807
title: A Post-hoc Analysis using Secondary Data of Clinical Trial from M14-033 Study to Evaluate Average Treatment Effect and Heterogeneous Treatment Effect of Adalimumab in Maintenance Phase for Patients with Ulcerative Colitis

description: Ulcerative colitis (UC) is one of the two primary forms of idiopathic inflammatory bowel disease. It is postulated that UC is caused by unregulated and exaggerated local immune response to environmental triggers in genetically susceptible individuals. UC is a chronic, relapsing inflammatory disease of the large intestine characterized by inflammation and ulceration of the mucosal and submucosal intestinal layers. The incidence in North America is estimated at 2.2 to 14.3 cases per 100,000 person-years with a prevalence of 37 to 246 cases per 100,000 persons. The burden of UC on the healthcare system is profound, accounting for nearly 500,000 physician visits and more than 46,000 hospitalizations per year in the United States (US) alone.
Adalimumab works by binding specifically to Tumor Necrosis Factor (TNF) - alfa, which is a signaling protein (also called a cytokine) that is released by white blood cells during inflammation that can trigger cell damage or cell death. By binding to TNF-alfa, adalimumab blocks the action of TNF-alfa, reducing inflammation and tissue destruction.
AbbVie received approval for the additional dosage and administration of Adalimumab high dose for adult Ulcerative Colitis (UC) indication on 27 September 2021 in Japan.  This approval allows Adalimumab 40 mg every week (ew) or Adalimumab 80 mg every other week (eow) in addition to the existing Adalimumab 40 mg eow during maintenance therapy for adult UC patients.  Since there is no specification in the package insert regarding dose selection during the maintenance phase, the dose is selected at the physician’s discretion in the clinical practice, taking into consideration the patient's symptoms and clinical course or the patient's preference for the drug.  Therefore, at present, there is no evidence to support dose selection of adalimumab in the maintenance phase, and it is unclear whether dose selection is appropriate.  From the perspective of personalized therapy, if a patient population that is expected to respond better to Adalimumab high doses can be identified, it may be possible to increase the probability of treatment success for patients by making evidence-based treatment selection.  This is a significant benefit for physicians and patients.
Observational and database studies using real world data may be possible ways to identify patient populations likely to respond better to Adalimumab high dose.  However, since Adalimumab high dose (40 mg ew or 80 mg eow) in maintenance therapy was only approved in September 2021, it takes long time to accumulate real world data for observational and database studies.  Therefore, we considered that the only data available at this time has been the clinical trial data from M14-033 Study sponsored by AbbVie. 
For the above reasons, we will attempt to identify the patient population expected to respond better to Adalimumab high dose by conducting a post-hoc analysis using the secondary data of the clinical trial from M14-033 Study.