No registrations found.
ID
Source
Brief title
Health condition
undifferentiated arthritis
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Percentage in remission at 3 months. 2. Percentage in sustained (at least 6 previous months) drug free remission.
Secondary outcome
Disease Activity Score (DAS) based on a 44 swollen joint count including a 53 joint Ritchie Articular Index.
Functional ability as measured by the Health Assessment Questionnaire (HAQ)
Physical and emotional wellbeing as measured by the ShortForm-36 (SF-36)
Functional ability in preferred activities as measured by the MACTAR
Quality of life as measured by the EuroQol 5-dimensional questionnaire (EQ-5D)
Toxicity as defined by number and severity of adverse events based on routine laboratory tests as required for study medications, open end questioning during study visits, and interim reports of adverse events
Local joint pain as measured on a 100 mm Visual Analogue Scale (VAS), measuring from 0 (no pain) to 100 (maximum imaginable pain)
General fatigue as measured on a 100 mm VAS (no to maximum)
Morning stiffness as measured on a 100 mm VAS (no to maximum)
General functional disability as measured on a 100 mm VAS (no to maximum)
Feelings of depression as measured with the Beck’s Depression Inventory
Treatment satisfaction as measured by the Treatment Satisfaction Questionnaire for Medication (TSQM)
Background summary
A newly diagnosed arthritis, where the cause is not yet clear (so-called undifferentiated arthritis, UA), can go into spontaneous remission, or become chronic and potentially progress to rheumatoid arthritis. At presentation it is not yet clear how things will develop, and therefore it is difficult to decide who to treat it. Suppression of symptoms with NSAIDs and a local corticosteroid injection may be sufficient, or it is necessary to start an antirheumatic treatment as rapidly as possible, to prevent progression and maybe induce cure. If the latter is true, we need to start with the most effective treatment, but which that is, is also not clear. Therefore we propose to invite patients with previously untreated undifferentiated arthritis to participate in this trial, where they will be randomized to either symptomatic treatment with NSAIDs and a local injection (arm 1), or to (as well) methotrexate, a slow-acting antirheumatic drug (arm 2), or baricitinib, a fast-acting antirheumatic drug (arm 3). Clinical evaluation by an independent joint assessor every three months will determine if remission is achieved or not. If not, medication will be changed: patients in arm 1 will be randomized to either arm 2 or arm 3, patients in arm 2 will switch to treatment according to arm 3, and vice versa. If remission is achieved on NSAIDs, they can be stopped. If remission is achieved on MTX, this can be stopped after an additional 6 months (for fear of relapse after stop), and if remission is achieved on baricitinib, patients will again be randomized, to either stop immediately, or continue for an additional 6 months. Total follow-up time per patient will be 18 months. There are 2 primary endpoints: percentage in remission at 3 months, and percentage in sustained (at least 6 previous months) drug free remission at 18 months.
Study objective
initial treatment with baricitinib results in more rapid remission and more sustained drug free remission compared to initial treatment with NSAIDs or methotrexate
Study design
February 2020 MEC approved, April 2020 first patient included, expected inclusion period 3 years, follow-up time per patients 18 months
Intervention
All arms: one intraarticular or intramuscular injection with corticosteroids (40 mg methylprednisolone or equivalent). Arm 1: start with NSAID (naproxen 2 dd 500 mg or equivalent). If no remission after 3 months: randomize to treatment according to arm 2 or arm 3. Arm 2: start with methotrexate 15 mg/week increased to 25 mg/week by week 4 or highest tolerated dose (oral or subcutaneous). NSAID or analgetic allowed. If no remission after 3 months: switch to baricitinib according to protocol of arm 3. In case remission is achieved on MTX: continue for 6 months then taper in 4 weeks to nil. In case of disease flare during or after tapering: switch to baricitinib. Arm 3: start with baricitinib 4 mg/day. NSAID or analgetic allowed. If no remission after 3 months: switch to methotrexate according to protocol of arm 2. In case remission is achieved on baricitinib: randomize to either immediate discontinuation or continuation for 6 more months. In case of disease flare after remission: switch to methotrexate.
Inclusion criteria
18 years or older, able to give written informed consent (in Dutch or English) and fill out questionnaires in Dutch (or English version, if available), undifferentiated arthritis with symptom duration <1 year, not fulfilling classification criteria for rheumatoid arthritis, other diagnoses causing the arthritis rejected, Disease Activity Score >1.6
Exclusion criteria
Contraindications to use of study medication or reasonable alternatives
Wish to become pregnant, breastfeed or father a child during the study
Alcohol- or substance abuse
Immuno-compromised state either based on co-morbidity or co-medication
Leucopenia <3*10^9/l, and/or neutropenia <1*10^9/l
Hemoglobin <5 mmol/l
Increased liver enzymes > 3x upper limit of normal
Renal insufficiency with estimated creatinine clearance <40%
Interstitial lung disease as seen on X-thorax
Maintenance treatment with corticosteroids exceeding prednisone 10 mg daily or equivalent
Active or ongoing chronic infection, (recurrent) serious infection(s) in past 4 months, latent TB who refuse anti-tuberculous treatment, hepatitis B with positive DNA viral load or hepatitis C with positive RNA viral load, patients with anti-HB2 and anti-HBc antibodies who refuse monitoring of hepatitis B DNA expression
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8195 |
| Other | METC LUMC : not yet available, EUDRACT nr is 2019-004359-35 |