JAK Inhibitor Dose TAPering Strategy Study

NCT06687551 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: RC31/23/03732023-509788-25-00
• Study Type: interventional
• Target: 308
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to assess the feasibility of tapering JAK inhibitors in rheumatoid arthritis patients in low disease activity by comparing a group of patients tapering the JAK inhibitor dosage to a group of patients continuing the full-dose. Participants will:

• Visit the clinic once every 3 months for checkups and tests
• Keep a diary of their treatment intake and symptoms

Conditions

Rhumatoid Arthisis

Keywords

JAK-inhibitor; dose reduction; Rheumatoid arthritis

Outcome Measures

Primary Outcomes (1)

• proportion of patients still receiving a JAK-inhibitor

  The primary outcome of this study will be the proportion of patients still receiving a JAK-inhibitor and being in CDAI low disease activity at 12 months. The size of the effect will be given in the form of the difference in proportion between the two treatment groups with a two-sided confidence interval at 95%. Non-inferiority will be assessed with this interval. Non-inferiority will be concluded if the lower limit of the 95% confidence interval does not exceed the non-inferiority margin of 10% of the difference in proportion.

  12 post baseline

Secondary Outcomes (1)

• Flare occurence

  first flare post baseline

Study Arms (2)

JAK inhibitor dose-tapering strategy

EXPERIMENTAL

The dose-tapering strategy will depend on the JAK inhibitor taken by the patient. It will be based on a 50% dose-reduction every 6 months and will comprise 2 steps: A. Treatment with baricitinib 4 mg daily: * Step 1 (after randomization): baricitinib 2mg daily. * Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): baricitinib 2mg every other day. B. Treatment with filgotinib 200 mg daily: * Step 1 (after randomisation): filgotinib 100 mg daily. * Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): filgotinib 100mg every other day. C. Treatment with tofacitinib 5 mg twice daily or tofacitinib 11mg daily: * Step 1 (after randomisation): tofacitinib 5 mg once daily. * Step 2 (in case of CDAI ≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): tofacitinib 5 mg every other day. D. Treatment with upadacitinib 15 mg daily: • Step 1 (after randomisat

Drug: Baricitinib (LY3009104) 4 mg; Drug: filgotinib 200mg/day; Drug: Tofacitinib 5 mg twice daily; Drug: Upadacitinib 15 MG

JAK inhibitor continuous therapy strategy

ACTIVE COMPARATOR

Full dose will be considered in patient taking: * Baricitinib 4mg/day * Filgotinib: 200mg/day * Tofacitinib : 5mg twice daily or 11mg/day * Upadacitinib: 15mg/day

Drug: Baricitinib (LY3009104) 4 mg; Drug: filgotinib 200mg/day; Drug: Tofacitinib 5 mg twice daily; Drug: Upadacitinib 15 MG

Interventions

Baricitinib (LY3009104) 4 mg DRUG

Treatment with baricitinib 4 mg daily * Step 1 (after randomization): baricitinib 2mg daily * Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): baricitinib 2mg every other day

JAK inhibitor dose-tapering strategy

filgotinib 200mg/day DRUG

Treatment with filgotinib 200 mg daily * Step 1 (after randomisation): filgotinib 100 mg daily * Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): filgotinib 100mg every other day

JAK inhibitor dose-tapering strategy

Tofacitinib 5 mg twice daily DRUG

Treatment with tofacitinib 5 mg twice daily or tofacitinib 11mg daily * Step 1 (after randomisation): tofacitinib 5 mg once daily * Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): tofacitinib 5 mg every other day

JAK inhibitor dose-tapering strategy

Upadacitinib 15 MG DRUG

Treatment with upadacitinib 15 mg daily * Step 1 (after randomisation): upadacitinib 15 mg every other day * Step 2 (in case of CDAI≤ 10 AND CRP level below the laboratory standard; 6 months after starting step1): upadacitinib 15 mg every 4 days

JAK inhibitor dose-tapering strategy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years at baseline.
• Rheumatoid arthritis defined by the ACR/EULAR criteria.
• Treated with a JAK inhibitor, full dose for at least 6 months.
• Being in LDA (CDAI≤10) for at least 6 months.
• Women of childbearing potential (WCBP) must have a negative pregnancy test before starting study
• Concomitant disease needing to be treated by the JAK inhibitor at full-dose (for example inflammatory bowel disease).
• Patient with a history of JAK-inhibitor dose reduction/spacing before enrollment in the study with the JAK-inhibitor currently being taken.
• Patient at risk for complication according to the ANSM (60) (current or past smokers, patients at risk of VTE, cancer or major cardiovascular problems, aged ≥ 65 years) at baseline AND currently taking baricitinib or filgotinib.
• Patient taking associated bDMARD (including anti-TNF, anti-IL6, anti-CD20, abatacept, anti-IL17, anti-IL12/23, anti-IL23, anti-IL1, anti-BAFF, anti-IL5 pathways).
• Patient taking immunotherapy for neoplasia.
• Surgery scheduled in the next 12 months.
• Fibromyalgia according to the physician's opinion.
• Anticipated poor compliance with the strategy.
• Patient with any condition that would prevent participation in the study and completion of the study procedures, including language limitation.
• Alcohol and/or drug misuse as determined by the investigator.

Sponsors & Collaborators

• University Hospital, Toulouse: lead

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

baricitinib; GLPG0634; tofacitinib; upadacitinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Adeline RUYSSEN-WITRAND, MD

CONTACT

05 61 77 56 26; ruyssen-witrand.a@chu-toulouse.fr

Delphine THUILLEZ

CONTACT

(+33 5 61 7)7 69 66; thuillez.d@chu-toulouse.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: This study will be a simple blinded trial, because the investigator in charge of the primary outcome assessment (CDAI) will be blinded to the randomisation arm. This independent investigator will also collect all the disease activity index (CDAI, SDAI and DAS28-ESR) in the other follow-up visits, since the results of the definition of the flares and strategy changes will be based on these disease activity index.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will take the format of a prospective therapeutic research. The design will be a pragmatic multicentre open-label simple-blinded, non-inferiority randomised controlled trial with two parallel groups, ratio 1:1, comparing the two following groups: 1. JAK inhibitor dose-tapering strategy. 2. JAK inhibitor continuous therapy strategy.

Study Record Dates

• First Submitted: October 29, 2024
• First Posted: November 13, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: November 13, 2024

Record last verified: 2024-11