Predictors for therapeutic outcomes in patients of ulcerative colitis receiving Janus kinase inhibitors

Lead Investigator: Shenghong Zhang, The first affiliated hospital of Sun Yat-sen University
Title of Proposal Research: Predictors for therapeutic outcomes in patients of ulcerative colitis receiving Janus kinase inhibitors
Vivli Data Request: 8775
Funding Source: This work was funded by the National Natural Science Foundation of China, grant/award number: 82070538 and 81870374
Potential Conflicts of Interest: None

Summary of the Proposed Research:
Ulcerative colitis (UC) is an immune-mediated disease characterised by chronic inflammation of the colon leading to bloody diarrhoea, frequent bowel movements, and tenesmus (the feeling that you need to pass stools, even though your bowels are already empty). Prevalence of UC in countries in the Western world exceed 0.5% and is as high as 0.75% in Canada and Scotland as of 2020. Moreover, the number of UC patients in Asia and Latin America has been rising rapidly in recent years. Fortunately, in the past 15 years, several new molecules have been introduced for the treatment of patients with moderate-to-severe UC. Janus kinase (JAK) inhibitors are a completely novel type of small molecular biological agents for the treatment of immune-mediated inflammatory diseases. A randomized controlled trial found that Filgotinib, an oral JAK1 preferential inhibitor, was efficacious in long-term clinical remission (where symptoms improve to the point where they are absent or almost gone) in approximately 37.2% of patients with moderately to severely active UC. However, some patient still had poor therapeutic outcomes during JAK inhibitor therapy. It has been found that more than half of UC patients failed to achieve clinical remission with induction and maintenance therapy with another JAK inhibitor, Tofacitinib. The induction phase is the initial high dose treatment to rapidly eliminate the symptoms of inflammation and the severity of the disease, and maintenance therapy is when a lower dose of drug is given to maintain the remission from the induction phase. As a result, predicting the long-term outcome of patients with early endpoints (signs of remission) of JAK inhibitor induction therapy will help patients selecting optimal treatment approaches and conducting personalized management. Some predictors are explored in the study of other biologics, such as faecal calprotectin (FC) – a protein found in faeces, patient-reported outcomes or PROs (including stool frequency and rectal bleeding score of the Mayo score) and c-reactive protein (CRP) in the blood. However, the predictive role of these predictors in JAK inhibitor-related therapies remains unclear. This study aims at investigating the predictive ability of in the JAK inhibitors-therapy inducing state for maintenance and long-term outcomes in UC. This analysis will include data from the clinical trials of SELECTION and OCTAVE. Analyses will be conducted to assess the relationships between common predictors and outcomes of interest, and evaluate the predictive ability of the corresponding predictors. The results may help in selecting treatment approaches with clinical benefit for patients.

Requested Studies:
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis
Data Contributor: Pfizer
Study ID: NCT01465763
Sponsor ID: A3921094

A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis.
Data Contributor: Pfizer
Study ID: NCT01458951
Sponsor ID: A3921095

A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As A Maintenance Therapy In Subjects With Ulcerative Colitis
Data Contributor: Pfizer
Study ID: NCT01458574
Sponsor ID: A3921096

Combined Phase 2b/3, Double-Blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Galapagos
Study ID: NCT02914522
Sponsor ID: GS-US-418-3898