JAK inhibitor dose TAPering strategy study in low disease activity rheumatoid arthritis patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

16 Jun 2025 → ongoing

Decision date (initial)

2024-06-03

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHU de Toulouse

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

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

Secondary objectives 10

1. To compare a tapering or spacing dose strategy versus therapy continuation on disease activity over time.
2. To compare a tapering or spacing dose strategy versus therapy continuation on the delay before a first flare
3. To compare a tapering or spacing dose strategy versus therapy continuation on the cumulative glucocorticoid dose at 12 months.
4. To compare a tapering or spacing dose strategy versus therapy continuation on pain, function, flares according to the patient’s perspective, fatigue and quality of life (patient reported outcomes) at 12 months.
5. To describe the structural progression over 12 months in both groups.
6. To describe the risk of adverse events and severe adverse events at 12 months (i.e. serious infections, major cardiovascular events, thromboembolic events, malignancies) in both groups.
7. To describe the proportion of patients in low disease activity at 12 months and who could reduce the JAK inhibitor in the dose-tapering arm.
8. To assess the risk factors of being in CDAI (Clinical Disease Activity Index) LDA (Low Disease Activity) at 12 months with a reduced dose of the JAK-inhibitor.
9. To assess the efficiency, at 12 months, of the JAK inhibitor dose-tapering strategy versus continuous therapy in RA patients with low disease activity using cost-utility and cost-effectiveness analyses, from the collective perspective.
10. To assess the impact of socioeconomic characteristics on the cost of care and the quality of life in each group at 12 months.

Conditions and MedDRA coding

Rheumatoid arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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

Exclusion criteria 17

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 (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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the proportion of patients still receiving a JAK-inhibitor and being in CDAI low disease activity at 12 months.

Secondary endpoints 9

1. Disease activity over time assessed by CDAI, SDAI and DAS28 scores.
2. The delay between the inclusion visit and the first flare diagnosed by a physician. Two definitions of flare will be assessed for this criterion: • A flare defined by a CDAI > 10 at any visit. • A major flare at any visit, based on the OMERACT definition which is: o An increase in the DAS28-ESR score of more than 1.2 compared to baseline score, o OR a DAS28-ESR score increase of more than 0.6 compared to the baseline score AND the current DAS28-ESR score being above 3.2.
3. The 12-month cumulative glucocorticoid dose including rescue short course of glucocorticoids and glucocorticoid joint injections.
4. Patient reported outcomes over 12 months including: • Pain assessed by a visual analogic scale of pain (VAS); • Function assessed by the Health Assessment Questionnaire (HAQ); • Flares according to the patient, assessed by the FLARE questionnaire • Fatigue assessed by a visual analogic scale of fatigue and the FACIT-F questionnaire • Quality of life assessed by the EQ-5D-5L and the RAID.
5. The modified van der Heijde Total Sharp Score variation between baseline visit and 12-month visit.
6. The number of adverse events and severe adverse events at 12 months.
7. The number and percentage of patients in CDAI low disease activity at 12 months who could reduce the JAK inhibitor dosage in the dose-tapering arm.
8. Incremental cost-utility and cost-effectiveness ratios (ICUR and ICER) from the collective perspective expressed in terms of cost per QALY for the ICUR and cost per patient without major flares for the ICER, at 12 months.
9. Occupation, level of income and level of education will be recorded to test the impact of socioeconomic characteristics on care costs and efficiency at 12 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

principal investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

principal investigator

Locations

1 EU/EEA country · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications