Filgotinib in the treatment of patients with ulcerative colitis: towards precision medicine (TOPS study)

Rationale: The traditional step-up strategy of treatment for inflammatory bowel
disease is changing rapidly with the introduction of new treatment modalities.
Two newly approved drugs inhibiting Janus kinase (JAK) - tofacitinib and
filgotinib- have been shown to be efficacious in inducing and maintaining
remission in patients with ulcerative colitis (UC). In the SELECTION study,
filgotinib 200mg once daily, performed significantly better than placebo for
inducing remission in both biological naïve and biological experienced patients
with UC (26.1% versus 15.3% and 11.5% versus 4.2%, respectively), while
remission rates at week 58 were 37.2% versus 11.2% in the respective placebo
group1. To date, head-to-head studies comparing efficacy and safety of
different classes of drugs and biomarkers enabling precision medicine are
presently lacking. Therefore, therapeutic choices are mostly based on
comorbidity, potential side effects, the need for a rapid onset of action and
costs. In the present study, we aim to identify and validate biological
predictors of clinical response to filgotinib in patients with UC. Furthermore,
we will establish a biobank, the TOPS Biobank, with the biological material of
patients, that will enable future inquiries into UC without subjecting subjects
to additional study measures.

Primary objective: identifying biomarkers for response to filgotinib in
patients with UC.
Secondary objective: To establish a biobank which can be used for future
inquiries into UC.

Observational, longitudinal, multicentre study with establishment of a biobank.

Study procedures
Endoscopy: Before initiating a step-up therapy, colonoscopy or flexible
sigmoidoscopy is routinely performed to confirm the presence of inflammation.
In addition, endoscopy is routinely performed after a follow-up of 20-24 weeks
and in case of a flare to assess mucosal healing or newly developed
inflammation. Whether a sigmoidoscopy or colonoscopy is chosen is decided by
the treating physician. During endoscopies eight mucosal biopsies will be
obtained for research purposes. Additionally, the patient will be asked to
undergo an additional proctoscopy with biopsies at week 10 (optional).

Blood/faeces: During treatment with filgotinib, blood and fecal samples are
routinely collected to monitor the treatment effect (CRP and fecal calprotectin
levels). Participation in the study will not result in more frequent blood
sampling. However additionally to the routine assessments, 42ml of blood and
two fecal samples will be collected at each time point. Time points will be at
baseline, at 4 weeks, at 10 weeks, at 24 weeks and 52 weeks or in case of a
flare.

Questionnaires: Patients will be asked to complete a short and validated
questionnaire (Mayo) for assessment of disease activity at each follow-up
moment (max.10 minutes, 5 times in total).

If the participant gives his/her consent, blood-, fecal- and tissue samples
will be stored in the TOPS Biobank.

Burden: Minimal as the endoscopies and blood sampling are part of the standard
of care. Additonal burden comes from filling in the quality of life
questionnaires which is minimal. If the participant agrees to partake in the
optional rectoscopy, a short and relatively burdenless procedure is added to
the standard of care.

Risks: Blood withdrawal carries a negligible risk of complications. The risk of
bleeding or perforation following the taking of biopsies during colonoscopy is
very low, approximately 1 per 1000 colonoscopies.