JAK Inhibitor Dose TAPering Strategy Study

NCT ID: NCT06687551

Last Updated: 2024-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

308 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-01

Study Completion Date

2029-04-01

Brief Summary

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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:

* Either take

1. JAK inhibitor dose-tapering strategy.
2. JAK inhibitor continuous therapy strategy.
* Visit the clinic once every 3 months for checkups and tests
* Keep a diary of their treatment intake and symptoms

Detailed Description

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Rheumatoid arthritis (RA) is an autoimmune disease leading to inflammation of the synovium and joint erosions, responsible for joint damage leading to pain, functional impairment, work loss and disability. The prognosis of the disease has been greatly improved for 20 years with the use of Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and especially biologic DMARDs.

It is recommended to target remission when initiating a DMARD and to assess patients according to a treat-to-target approach in order to adapt therapy. Once sustained remission is achieved, a decrease in the targeted therapeutic DMARD dose should be considered, according to the recommendations, in order to reduce the risk of adverse events and medical costs. Indeed, targeted DMARDs have considerably increased medical costs linked to RA and studies assessing medical economic impact of bDMARD down-titration on medical costs highlighted the cost-utility of such strategies.

JAK inhibitors, a novel class of targeted therapies have proved to be very effective in treating inflammation and preventing structural progression in RA. However, awareness has recently been raised regarding the safety of JAK inhibitor in the treatment of RA, with particular emphasis on tofacitinib. Indeed, tofacitinib seems to increase the risk of thromboembolism events, infections, neoplasia and major cardiovascular events in comparison to anti-TNF in RA, with a dose-effect.

To date, we have very little data regarding the feasibility of a JAK inhibitor dose-tapering strategy. As a dose-related effect was apparent in terms of major adverse events, we assume that JAK inhibitor dose-tapering strategy might reduce the risk of serious adverse events, without increasing the risk of major flares and thus be beneficial for the patient.

The aim of the study will be to compare a dose-tapering strategy versus therapy continuation in rheumatoid arthritis patients in low disease activity treated with JAK inhibitors on the risk of losing low disease activity despite rescue therapy at 12 months.

1\) 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 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.

Management of flares:

1. In case of flare, diagnosed during a scheduled visit: the management of the flare will be standardized by a rescue therapy including a glucocorticoid course and returning to the previous step of JAK inhibitor dose. If the flare is not resolved after the rescue therapy, the patient will be considered in failure of the strategy.
2. In case of flare between two scheduled visits, an additional visit will be scheduled by the clinical center to confirm the flare by the physician. If the flare is confirmed, the patient will have the standardized flare management as described above.

2\) Patients randomised to the control group will have to continue the JAK inhibitor at full dose until the end of the protocol:

* In case of baricitinib: baricitinib 4mg/day.
* In case of filgotinib: filgotinib 200mg/day.
* In case of tofacitinib: tofacitinib 5mg twice daily or 11mg/day.
* In case of upadacitinib: upadacitinib 15mg/day.

Management of flares:

1. In case of flare, diagnosed during a scheduled visit: the management of the flare will be standardized by a rescue therapy with a glucocorticoid course. If the flare is not resolved after the rescue therapy, the patient will be considered in failure of the strategy.
2. In case of flare between two scheduled visits, an additional visit will be scheduled by the clinical center to confirm the flare by the physician. If the flare is confirmed, the patient will have the standardized flare management as described above.

Patients with co-medication with sDMARD or glucocorticoids \< 5mg/d will have to keep a stable dose of their treatment during the 12 months of the study in both groups.

Conditions

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Rhumatoid Arthisis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators
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.

Study Groups

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JAK inhibitor dose-tapering strategy

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

Group Type EXPERIMENTAL

Baricitinib (LY3009104) 4 mg

Intervention Type 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

filgotinib 200mg/day

Intervention Type 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

Tofacitinib 5 mg twice daily

Intervention Type 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

Upadacitinib 15 MG

Intervention Type 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 continuous therapy strategy

Full dose will be considered in patient taking:

* Baricitinib 4mg/day
* Filgotinib: 200mg/day
* Tofacitinib : 5mg twice daily or 11mg/day
* Upadacitinib: 15mg/day

Group Type ACTIVE_COMPARATOR

Baricitinib (LY3009104) 4 mg

Intervention Type DRUG

use of JAK inhibitor at full dose until the end of the protocol

filgotinib 200mg/day

Intervention Type DRUG

use of JAK inhibitor at full dose until the end of the protocol

Tofacitinib 5 mg twice daily

Intervention Type DRUG

use of JAK inhibitor at full dose until the end of the protocol

Upadacitinib 15 MG

Intervention Type DRUG

use of JAK inhibitor at full dose until the end of the protocol

Interventions

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Baricitinib (LY3009104) 4 mg

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

Intervention Type DRUG

filgotinib 200mg/day

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

Intervention Type DRUG

Tofacitinib 5 mg twice daily

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

Intervention Type DRUG

Upadacitinib 15 MG

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

Intervention Type DRUG

Baricitinib (LY3009104) 4 mg

use of JAK inhibitor at full dose until the end of the protocol

Intervention Type DRUG

filgotinib 200mg/day

use of JAK inhibitor at full dose until the end of the protocol

Intervention Type DRUG

Tofacitinib 5 mg twice daily

use of JAK inhibitor at full dose until the end of the protocol

Intervention Type DRUG

Upadacitinib 15 MG

use of JAK inhibitor at full dose until the end of the protocol

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Aged ≥ 18 years at baseline.
2. Rheumatoid arthritis defined by the ACR/EULAR criteria.
3. Treated with a JAK inhibitor, full dose for at least 6 months.
4. The JAK inhibitor is prescribed as monotherapy or combined with a csDMARD with a stable dosage for at least 3 months before inclusion.
5. Being in LDA (CDAI≤10) for at least 6 months.
6. With a CRP level below the laboratory standard within the month before the inclusion visit.
7. Women of childbearing potential (WCBP) must have a negative pregnancy test before starting study


1. Concomitant disease needing to be treated by the JAK inhibitor at full-dose (for example inflammatory bowel disease).
2. Patient with a history of JAK-inhibitor dose reduction/spacing before enrollment in the study with the JAK-inhibitor currently being taken.
3. Evidence of flare-up within the last 6 months prior to the inclusion.
4. Patient who received glucocorticoids \> 5mg/day in the 3 months prior the inclusion because of the disease activity of the RA.
5. Patient requiring corticoid joint injections in the 3 months prior to inclusion or with scheduled joint injections, to control disease activity.
6. 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.
7. 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).
8. Patient taking immunotherapy for neoplasia.
9. Surgery scheduled in the next 12 months.
10. Fibromyalgia according to the physician's opinion.
11. Anticipated poor compliance with the strategy.
12. Patient with any condition that would prevent participation in the study and completion of the study procedures, including language limitation.
13. Alcohol and/or drug misuse as determined by the investigator.
14. Pregnancy or breastfeeding.
15. Non-affiliation to the French Social Security System.
16. Patient unwilling to sign the informed consent form.
17. Patient under legal protection.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Toulouse

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Central Contacts

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Adeline RUYSSEN-WITRAND, MD

Role: CONTACT

05 61 77 56 26

Delphine THUILLEZ

Role: CONTACT

(+33 5 61 7)7 69 66

Other Identifiers

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2023-509788-25-00

Identifier Type: CTIS

Identifier Source: secondary_id

RC31/23/0373

Identifier Type: -

Identifier Source: org_study_id

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