Real-world Effectiveness of Tofacitinib on Ulcerative Colitis Associated Spondyloarthropathy (RETUCAS)

Efficacia Nel Mondo Reale di Tofacitinib Sulla Spondiloartropatia Associata Alla Colite Ulcerosa

Tofacitinib (TOFA) is a JAK inhibitor already used in rheumatology for the treatment of moderate-to-severe active rheumatoid arthritis and psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease- modifying antirheumatic drugs. Furthermore, TOFA has been recently approved for the treatment of adult patients with moderate-to-severe active Ulcerative Colitis (UC) who had no response, lose response, or were intolerant to either conventional therapy or a biologic agent. The approval was based on the efficacy demonstrated by TOFA in three phase 3 randomized controlled trials named OCTAVE: two identically designed, 8-week, placebo- controlled, induction studies of oral TOFA 10 mg twice daily followed by the OCTAVE Sustain 52-week maintenance study. About sacroiliitis, 2 out of 8 patients treated with TOFA improved after 8 weeks, compared with 0 out of 3 patients in the placebo group. Obviously, these data should be interpreted with extreme caution since patient numbers were very low, and it should be again emphasized that these trials were not designed to explore the efficacy of TOFA onextraintestinal manifestations.

On these premises, we designed a prospective, multicenter, observational, 52-week study with the aim of assess the effectiveness of TOFA on UC-associated spondyloarthropathy.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis; Spondyloarthropathy
• Intervention / Treatment: Drug: Tofacitinib

Detailed Description

Participants will receive TOFA at study entry (week 0) as treatment for UC according to standard clinical practice and recommended dosage of the drug, and will be followed up to 52 weeks. At baseline, all enrolled patients will undergo a detailed assessment including gender, age, duration of disease, smoking status, extension of disease (according to Montreal classification), clinical activity (assessed with the partial Mayo Score), C-Reactive Protein (CRP) values, faecal calprotectin, previous and concomitant therapies, data on SpA (axial vs. peripheral SpA, and assessment of ASDAS-CRP and/or DAS28-CRP scores). The joint response (JR), steroid free joint response (SFJR), clinical intestinal response (CIR), steroid free clinical intestinal remission (SFCIR), CRP and calprotectin values will be assessed at 8, 24 and 52 weeks (see further for the definitions of the outcomes). The burden of UC and therapy with TOFA on work productivity and health- related quality of life will be evaluated through the administration of the Work Productivity and Activity Impairment (WPAI) Questionnaire and the Short Inflammatory Bowel Disease Questionnaire Score (Short IBDQ), respectively, at baseline and at 24 and 52 weeks. The patients will be assessed with direct visits and biochemical evaluations, including monitoring of serum lipid levels, according to the routine clinical practice established for subjects treated with TOFA. The support by a rheumatologist is suggested in the clinical evaluation of patients All data will be collected anonymously in a specifically arranged eCRF form inside the IG-IBD registry.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Carola Lauritano; Phone Number: +393397793868; Email: ctm@igibd.it

Study Locations

• Italy
  • Palermo, Italy
    • Recruiting
    • IBD Unit, Department of Internal Medicine, "Villa Sofia-Cervello" Hospital
    • Contact: Macaluso Fabio, MD; Email: fsmacaluso@gmail.com
    • Principal Investigator: Macaluso Fabio, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients aged 18 years or older admitted at each IG-IBD center that agrees to participate could be be screened for inclusion

Description

Inclusion Criteria:

• An established diagnosis of UC and an established diagnosis of axial and/or peripheral SpA according to the Assessment of Spondyloarthritis international Society (ASAS) criteria
• Indication for treatment with TOFA as a therapy for UC according to the clinical practice and summary of product characteristics
• Active SpA at baseline assessed with an Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP ≥ 1.3 in case of axial SpA, and with a disease activity score (DAS)28-CRP ≥ 2.6 in case of peripheral SpA.
• Capability to express a written informed consent for the study

Exclusion Criteria:

Rheumatologic diseases other than UC-associated SpA (for example, previous diagnosis of rheumatoid arthritis or psoriatic arthritis)

• Inactive SpA at baseline
• Inability to understand or sign the informed consent
• Contraindications to treatment with TOFA (pregnancy, risk factors for venous thromboembolism, active infections, hepatic failure)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
joint response and steroid free joint response	evaluate the rate of patients achieving joint response and steroid free joint response on Ulcerative Colitis-associated spondyloarthropathy at week 8, 24, and 52	week 8
joint response and steroid free joint response	evaluate the rate of patients achieving joint response on Ulcerative Colitis-associated spondyloarthropathy	week 24
joint response and steroid free joint response	evaluate the rate of patients achieving joint response and steroid free joint response on Ulcerative Colitis-associated spondyloarthropathy	week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical intestinal response CIR	To assess the rate of patients achieving a clinical intestinal response CIR for Ulcerative Colitis	week 8
clinical intestinal response CIR	To assess the rate of patients achieving a clinical intestinal response CIR for Ulcerative Colitis	week 24
clinical intestinal response CIR	To assess the rate of patients achieving a clinical intestinal response CIR for Ulcerative Colitis	week 52
steroid free clinical intestinal remission	To assess the rate of patients achieving a steroid free clinical intestinal remission for Ulcerative Colitis	week 52
impact of Ulcerative Colitis	To assess the impact of Ulcerative Colitis and therapy with TOFA on Work Productivity and Activity Impairment through the administration of WPAI Questionnaire at baseline	week 8
impact of Ulcerative Colitis	To assess the impact of Ulcerative Colitis and therapy with TOFA on Work Productivity and Activity Impairment through the administration of WPAI Questionnaire at baseline	week 24
impact of Ulcerative Colitis	To assess the impact of Ulcerative Colitis and therapy with TOFA on Work Productivity and Activity Impairment through the administration of WPAI Questionnaire at baseline	week 52
health-related quality of life	To assess the health-related quality of life of the patients with the administration of the Short IBDQ at baseline	week 24 and 52
health-related quality of life	To assess the health-related quality of life of the patients with the administration of the Short IBDQ at baseline	week 52
adverse events	To report the rate of adverse events with TOFA	24 month
redictors of joint response JR, steroid free joint response SFJR, clinical intestinal response CIR, and steroid free clinical intestinal remission SFCIR	To assess the predictors of joint response JR, steroid free joint response SFJR, clinical intestinal response CIR, and steroid free clinical intestinal remission SFCIR	24 month

Collaborators and Investigators

• Sponsor: Italian Group for the study of Inflammatory Bowel Disease (IG-IBD)

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: April 6, 2022
• First Submitted That Met QC Criteria: June 21, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): June 24, 2022
• Last Update Submitted That Met QC Criteria: June 21, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Gastrointestinal Diseases; Joint Diseases; Musculoskeletal Diseases; Gastroenteritis; Arthritis; Colonic Diseases; Intestinal Diseases; Spinal Diseases; Bone Diseases; Inflammatory Bowel Diseases; Bone Diseases, Infectious; Ulcer; Colitis; Colitis, Ulcerative; Spondylitis; Spondylarthritis; Spondylarthropathies; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: 007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No