DOI: 10.25934/pr00007656
title: Impact of Steroid Weaning Regimens on Outcomes in Clinical Trials of Ulcerative Colitis 

description: Ulcerative colitis (UC) is a type of inflammatory bowel disease that affects the large intestine. Patients with UC experience symptoms such as diarrhea, rectal bleeding, abdominal pain, and urgency.  Patients with severe disease or those who lack response to corticosteroids are candidates for biologic and small molecule treatments.
 
Vedolizumab and adalimumab are two biologic therapies that have been approved for the treatment of moderate-to-severe UC on the strength of several placebo-controlled trials demonstrating efficacy and ability to maintain response, including ACT 1 (NCT00036439) and ACT 2 (NCT00096655), ULTRA 2 (NCT00408629), and GEMINI 1 (NCT00783718).  Recently, the VARSITY trial (NCT02497469) was a head-to-head trial that demonstrated the superiority of vedolizumab to adalimumab in moderate-to-severe UC. Golimumab is another biologic therapy that demonstrated efficacy in PURSUIT (NCT00488631), which was a placebo-controlled trial. In addition to biologic therapies, small molecule therapies are a treatment option that has recently emerged. Tofacitinib was recently approved on the strength of the placebo-controlled OCTAVE trials (NCT01465763, NCT01458951, and NCT01458574).

The Mayo Score is a tool that is used in clinical practice and trials to determine the severity of UC and is comprised of several patient-reported and endoscopic sub-scores, including stool frequency, rectal bleeding, endoscopic findings, and physician’s global assessment. Each subscore is scored from 0 to 3, with higher scores indicating greater disease severity. The total Mayo Score ranges from 0 to 12, while the partial Mayo Score excludes the endoscopic subscore and thus ranges from 0 to 9. The Mayo Score is widely used in clinical trials for UC to evaluate primary endpoints, such as clinical remission (CR). Corticosteroid-free CR is also an important endpoint and is often included as part of co-primary or secondary endpoints.

Patients enrolled in trials often require corticosteroids at the time of entry to manage their symptoms. Corticosteroid use can reduce symptoms that indicate active disease and therefore its use can impact outcomes in clinical trials. However, protocols for managing steroids during trials vary. In the VARSITY trial, steroid tapering was adaptive and up to the physician’s discretion. Other trials implement a fixed steroid tapering protocol that must be strictly adhered to. Although trials must transparently document steroid tapering protocols, there remains a lack of consistent or standardized tapering definitions across trials. Therefore, it remains unclear what impact steroid tapering protocols have on trial outcomes.

The primary objective of this study is to evaluate whether differences in steroid tapering regimen between clinical trials influenced one-year corticosteroid-free CR among patients with steroid use at baseline. The secondary objectives of this study include CR at one-year and corticosteroid-free CR among all patients, regardless of baseline steroid use. 
Patient-level data from ULTRA 2, GEMINI 1, VARSITY, and OCTAVE is being requested from Vivli. Patient-level data from ACT 1, ACT 2, and PURSUIT is being requested from the YODA Project.

Patients may benefit from the knowledge generated from this study as it may inform criteria for steroid tapering protocols in clinical trials. By extention, knowledge generated from this study may help patients better understand how concomitant use of steroids may impact their likelihood of achieving favourable outcomes in the future.