Comparing the effectiveness of morning and evening dosing of tofacitinib in inflammatory arthritis
| ISRCTN | ISRCTN68663074 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68663074 |
| EudraCT/CTIS number | 2021-004131-84 |
| Secondary identifying numbers | ChronIA001 |
- Submission date
- 25/11/2021
- Registration date
- 22/12/2021
- Last edited
- 16/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims:
Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. Disruption of the circadian rhythm may lead to immune system dysregulation. In line with this, various inflammatory arthritis symptoms show a distinctive daily pattern, including pain and joint stiffness. However, in daily practice we often do not take advantage of these circadian rhythms, especially not with regard to treatment. The aim of this study is to compare the effectiveness of tofacitinib morning versus evening dosing in rheumatoid arthritis and psoriatic arthritis patients.
Who can participate?
Patients aged 18 years or older with rheumatoid arthritis or psoriatic arthritis with active disease
What does the study involve?
Patients are randomly allocated to morning or evening dosing of tofacitinib for 3 months, which is followed by switching to the other treatment schedule for the next 3 months. Patients will be assessed at the start of the study and after 1, 3 and 6 months of treatment. At each visit patients will fill out online questionnaires and are seen by the research nurse. Additional blood and faecal samples will be taken at the start of the study and after 1 month (only blood), 3 and 6 months. Finally, patients will wear an actigraph (like a wristwatch) on their wrist two times for 2 weeks at home. The actigraph will be picked up by the patient in the hospital 2 weeks before the visit.
What are the possible benefits and risks of participating?
If successful, this study will show the best dosing time of tofacitinib and could be a step towards the use of this treatment on a regular basis in daily practice. It may also help better address well-known problems such as morning stiffness and fatigue, which often persist after reaching low disease activity.
Tofacitinib is approved and used according to the label so evening dosing of tofacitinib should not lead to any greater risks compared to morning dosing (routine care).
Where is the study run from?
Erasmus Medical Center, Rotterdam (The Netherlands)
When is the study starting and how long is it expected to run for?
January 2021 to October 2026
Who is funding the study?
Pfizer B.V. (USA)
Who is the main contact?
Dr P.H.P. de Jong
p.h.p.dejong@erasmusmc.nl
Contact information
Scientific
Dr. Molewaterplein 40
Rotterdam
3015 GD
Netherlands
| Phone | +31 (0)10 7038251 |
|---|---|
| p.h.p.dejong@erasmusmc.nl |
Public
Dr. Molewaterplein 40
Rotterdam
3015 GD
Netherlands
| Phone | +31 (0)610641598 |
|---|---|
| s.snoeckhenkemans@erasmusmc.nl |
Study information
| Study design | Open-label randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Chronotherapy in Inflammatory Arthritis: a randomized controlled trial comparing the effectiveness of morning and evening dosing of tofacitinib extended-release |
| Study acronym | ChronIA |
| Study objectives | Evening dosing of tofacitinib XR will lead to a lower (self-reported) disease activity and improve sleep quality, morning stiffness and pain compared to morning dosing, because it is better synced with the circadian rhythm of inflammatory cytokines. |
| Ethics approval(s) | Approved 14/02/2022, Medisch Ethische Toetsings Commissie (METC) Erasmus Medical Center (Postbus 2040, 3000 CA Rotterdam, the Netherlands; +31 107033625; metc@erasmusmc.nl), ref: NL78735.078.21 |
| Health condition(s) or problem(s) studied | Inflammatory arthritis (rheumatoid arthritis and psoriatic arthritis) |
| Intervention | Patients will be randomized using minimization randomization stratified for diagnosis and co-medication. Patients are randomized into morning or evening dosing of tofacitinib XR (11 mg q.d.) for 3 months, which is followed by switching to the alternate regimen for the next 3 months. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Tofacitinib extended release |
| Primary outcome measure | Disease activity measured with the Routine Assessment of Patient Index Data 3 (RAPID3) at 3 months |
| Secondary outcome measures | Current secondary outcome measures as of 21/11/2023: 1. (Self-reported) disease activity (states) measured using Disease Activity Score (DAS) & Disease activity in PSoriatic Arthritis (DAPSA) at 3 and 6 months 2. Sleep measured using a sleep scale from the medical outcomes study (MOSS-ss) at 3 and 6 months 3. Morning stiffness (severity and duration) measured using a 10-point Likert scale at 3 and 6 months 4. Pain measured using a visual analogue scale (VAS) and the generalized pain questionnaire (GPQ) at 3 and 6 months 5. Fatigue measured using a visual analogue scale (VAS) and the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at 3 and 6 months 6. General health measured using a visual analogue scale (VAS) at 3 and 6 months 7. Functional ability measured using the health assessment questionnaire disability index (HAQ-DI) at 3 and 6 months 8. Quality of life measured using EuroQoL (EQ-5D-5L) at 3 and 6 months 9. Worker productivity measured using the Work Productivity and Activity Impairment (WPAI) at 3 and 6 months 10. Treatment satisfaction measured using a visual analogue scale (VAS) at 3 and 6 months 11. Compliance measured using the Medication Adherence Report Scale (MARS-5) at 3 and 6 months Previous secondary outcome measures: 1. (Self-reported) disease activity (states) measured using Disease Activity Score (DAS) & Disease activity in PSoriatic Arthritis (DAPSA) at 3 and 6 months 2. Sleep measured using a sleep scale from the medical outcomes study (MOSS-ss) at 3 and 6 months 3. Morning stiffness (severity and duration) measured using a 10-point Likert scale at 3 and 6 months 4. Pain measured using a visual analogue scale (VAS) at 3 and 6 months 5. Fatigue measured using a visual analogue scale (VAS) and the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at 3 and 6 months 6. General health measured using a visual analogue scale (VAS) at 3 and 6 months 7. Functional ability measured using the health assessment questionnaire disability index (HAQ-DI) at 3 and 6 months 8. Quality of life measured using EuroQoL (EQ-5D-5L) at 3 and 6 months 9. Worker productivity measured using the Work Productivity and Activity Impairment (WPAI) at 3 and 6 months 10. Treatment satisfaction measured using a visual analogue scale (VAS) at 3 and 6 months 11. Compliance measured using the Medication Adherence Report Scale (MARS-5) at 3 and 6 months |
| Overall study start date | 01/01/2021 |
| Completion date | 31/10/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 84 |
| Key inclusion criteria | Current inclusion criteria as of 21/11/2023: 1. Age ≥18 years 2. Diagnosed with rheumatoid arthritis (RA) or psoriatic arthritis (PsA), according to respectively the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria for RA and ClASsification for Psoriatic ARthritis (CASPAR) criteria 3. Active disease, defined as a Disease Activity Score (DAS) >2.4 or Disease Activity in PSoriatic Arthritis (DAPSA) score >14 Previous inclusion criteria: 1. Age ≥18 years 2. Diagnosed with rheumatoid arthritis (RA) or psoriatic arthritis (PsA), according to respectively the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria for RA and ClASsification for Psoriatic ARthritis (CASPAR) criteria 3. Active disease, defined as a Disease Activity Score (DAS) >2.4 or Disease Activity in PSoriatic Arthritis (DAPSA) score >14 4. Biological disease-modifying antirheumatic drug (bDMARD) usage <3 |
| Key exclusion criteria | 1. Current or previous treatment with a targeted synthetic (ts)DMARD 2. Prednisone (or equivalent) at a dose of >7.5 mg 3. (Relative) contraindications for the study medication 4. Work in shifts 5. Not being able to understand, speak and write in Dutch |
| Date of first enrolment | 01/03/2022 |
| Date of final enrolment | 31/12/2024 |
Locations
Countries of recruitment
- Netherlands
Study participating centres
Rotterdam
3015 GD
Netherlands
Capelle aan den IJssel
2906 ZC
Netherlands
Sponsor information
Hospital/treatment centre
Dr. Molewaterplein 40
Rotterdam
3015 GD
Netherlands
| Phone | +31 (0)107034694 |
|---|---|
| r.dolhain@erasmusmc.nl | |
| Website | https://www.erasmusmc.nl/en/research/departments/rheumatology |
"ROR" |
https://ror.org/018906e22 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Pfizer Inc., Pfizer Consumer Healthcare, Davis, Charles Pfizer & Company, Warner-Lambert, King Pharmaceuticals, Wyeth Pharmaceuticals, Seagen
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/12/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. Plans for sharing additional documents are currently unknown. |
| IPD sharing plan | The current data-sharing plans for this study are unknown and will be available at a later date. |
Editorial Notes
16/01/2025: The following changes were made to the trial record:
1. The overall end date was changed from 01/07/2025 to 31/10/2026.
2. The intention to publish date was changed from 31/12/2025 to 31/12/2027.
3. The plain English summary was updated to reflect these changes.
21/11/2023: The secondary outcome measures and inclusion criteria were updated. IJsselland Hospital was added to the study participating centres.
22/03/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/02/2022 to 01/03/2022.
2. The ethics approval has been updated.
11/01/2022: The recruitment start date was changed from 01/01/2022 to 01/02/2022.
30/11/2021: Trial's existence confirmed by the Central Committee on Research Involving Human Subjects (CCMO).
