Retrospective Observational Comparison Study Between Ustekinumab and Tofacitinib as Third Line Therapy in a Multicenter Cohort of Patients With Refractory Ulcerative Colitis.

Sponsor
IRCCS San Raffaele
Study ID
NCT05728008
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Ustekinumab — DRUG
    a human monoclonal antibody to interleukin IL 12/23 p40. It is indicated in the treatment of adult patients with moderately to severely active UC. The induction phase consists of approximately 6 mg/kg intravenous dose administration. After the induction, the maintenance phase consists of a 90mg subcutaneous dose every 8 weeks.
  • Tofacitinib — DRUG
    Jak inhibitor. It is indicated in the treatment of adult patients with moderately to severely active UC who have experienced inadequate response or have lost the response or who are intolerant to conventional therapy or to a biological agent. The induction phase consists of 10mg twice daily for 8 to 16 weeks. After the induction, the maintenance phase consists of 5mg x twice daily.

Study Details

Ulcerative colitis (UC) is a chronic remitting and relapsing inflammatory bowel disease. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. It is diagnosed through colonoscopy and histological evidence of mucosal inflammation involving predominantly the rectum and potentially extending continuously up to the proximal segments of the colon. The patients affected present with severe abdominal pain, bloody diarrhea together with extraintestinal manifestations such as peripheral arthritis, pyoderma gangrenosum, erythema nodosum, ankylosing spondylitis and many others. The last 20 years have been profitable from the therapeutical point of view thanks to the advent of biological drugs which are derived from a living organism or its products including antibodies, interleukins and other molecules capable to target specific cellular pathways and to modulate different mechanisms such as blocking the actions of cytokines or white cells movement in the gut. More recently new promising alternatives seems to be the so-called small molecule drugs which are chemically derived low molecular weight compounds capable to enter the cell to regulate its functions and more generally biological processes like inflammation. In the last years, the therapeutic offer for ulcerative colitis patients has been enriched with the advent of biologics with different mechanism of action and very recently with the availability of the small molecules. Currently the available therapeutic options for ulcerative colitis include topic and systemic mesalazine, topic and systemic glucocorticoids, immunosuppressants (thiopurines), biological drugs (anti-tumor necrosis factor α (TNFα), inhibitor of α4β7 integrin, anti-IL12-23) and small molecules (JAK inhibitors). However, if on the one hand the therapeutical enrichment has clearly improved the disease rate control, still there is the need to perform sequencing study to stratify the available options to provide the best and most appropriate patient-oriented management.

Key Dates

Start date
Apr 5, 2022
Status verified
Jan 2023
Primary completion
Jun 5, 2022
Completion
Jul 5, 2022

Study Design

Enrollment
100 participants (actual)

Arms

  • Arm: subject treated with ustekinumab (anti-IL12-23)
    subjects treated with ustekinumab (anti-IL12-23) and have a follow-up at 24 +/- 4 weeks from the start of the third line therapy
  • Arm: subject treated withtofacitinib (pan JAK inhibitor)
    subjects treated with tofacitinib (pan JAK inhibitor) and have a follow-up at 24 +/- 4 weeks from the start of the third line therapy.

Primary Outcome Measure

Determine which drug between ustekinumab and tofacitinib as a third-line treatment, in cases refractory to both anti-TNFα and vedolizumab, is the best option to achieve disease control in terms of hospitalization rate, surgery rate, drug optimization. [ Time Frame: 2 months ]

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