BAriCitinib Healing Effect in earLy pOlymyalgia Rheumatica

Study Overview
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Brief Summary
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Patients with recent PMR(6 months or less) with a PMR-AS >17 and no oral or parenteral GCs during the past 2 weeks (at least) will be included. Treatment with oral baricitinib 4mg or placebo during 12 weeks and then, if PMR-AS≤10, they will receive baricitinib 2 mg for 12 weeks and then will stop treatment. No rescue is allowed before week 4 (visit 3) but patients may receive up to 2 intra-articular or soft tissue injections of GCs until week 4 according to investigator's opinion. From week 4 to week 12, steroids will be proposed as a rescue for both arms at investigators' discretion and according to PMR-AS.

Official Title
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BAriCitinib Healing Effect in earLy pOlymyalgia Rheumatica (BACHELOR Study)

Conditions
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Polymyalgia Rheumatic (PMR)

Intervention / Treatment
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* Drug: Baricitinib
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 50 years of age Fulfilling ACR/EULAR criteria for PMR Disease duration ≤6 months No oral or parenteral steroid since ≥ 2 weeks prior to randomization PMR-AS >17 Absence of connective tissue diseases or vasculitis Able to give informed consent Exclusion Criteria: Clinical symptoms of giant cell arteritis Uncontrolled high blood pressure or cardiovascular disease Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to PMR Planned major surgical procedure during the study. History of malignant neoplasm within the last 5 years (or 3 years in case of cervical carcinoma, basal cell or squamous epithelial skin cancer resected with no evidence of recurrence or metastatic disease). Current active uncontrolled infection Detailed exclusion criteria related to prior or concomitant therapy, general safety and laboratory data are reported in the protocol

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multicenter double blinded randomized placebo controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Oral baricitinib 4mg/day for 12 weeks. Then, at week 12, if PMR-AS≤10, patients will receive baricitinib 2 mg for 12 weeks. If PMR-AS ≤10, the patients will not receive any treatment until W24 At W24, if PMR-AS>10, they will receive GCs according to the PMR-AS (PMR-AS<10: no GCs, PMR-AS between 10-20: 10mg/day, PMR-AS between 21-30: GCs at 15mg/d and if PMR-AS> 30: 20mg/d or more according to investigator's opinion). Dosage of GCs will be decreased (1 mg every week) or increased according to PMR-AS (PMR-AS < 10: decrease, PMR-AS > 20 increase, 10 ≤ PMR-AS ≤ 20: stable dose) according to investigator's opinion. | Drug: Baricitinib<br>* patient will take a tablet of 4 mg/d during 12 weeks and then 2 mg/d during 12 weeks if the patient achieves PMR-AS≤ 10 at week 12<br>|
| Placebo Comparator: Control group<br>Oral placebo every day during 3 months (W12). Then, at week 12, if PMR-AS ≤10, placebo for 12 weeks. If PMR-AS ≤10, the patients do not receive any treatment until a flare. If PMR-AS>10, they will receive GCs according to the PMR-AS (PMR-AS<10: no GCs, PMR-AS between 10-20: 10mg/day, PMR-AS between 21-30: GCs at 15mg/d and if PMR-AS> 30: 20mg/d or more according to investigator's opinion). Dosage of GCs will be decreased (1mg every week) or increased according to PMR-AS (PMR-AS < 10: decrease, PMR-AS > 20 increase, 10 ≤ PMR-AS ≤ 20: stable dose) and according to investigator's opinion. | Drug: Placebos<br>* patient will take a tablet of 4 mg/d during 12 weeks and then 2 mg/d during 12 weeks if the patient achieves PMR-AS≤ 10 at week 12<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Following of the Polymyalgia Rheumatica Activity score | The activity of Polymyalgia Rheumatica is evaluated using the Polymyalgia Rheumatica Activity score (PMR-AS), a disease activity score based on morning stiffness, ability to elevate the upper limbs, physician's global disease assessment , Visual Analog Score for patient's pain (VAS), and CRP level. The PMR-AS is considered as relevant to define relapse and remission but also to decide if treatment have to be decreased, unchanged or increased (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Following of the Polymyalgia Rheumatica Activity score | The activity of Polymyalgia Rheumatica is evaluated using the Polymyalgia Rheumatica Activity score (PMR-AS), a disease activity score based on morning stiffness, ability to elevate the upper limbs, physician's global disease assessment , Visual Analog Score for patient's pain (VAS), and CRP level. The PMR-AS is considered as relevant to define relapse and remission but also to decide if treatment have to be decreased, unchanged or increased (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose) | 36 weeks | 
| Emergence of adverse events (Safety and tolerability) | The safety is evaluated with the adverse events in both arms | 36 weeks | 
| Following of the cumulative dosages of Glucocorticoids | dosages of GCs | 36 weeks | 
| ultrasound of synovitis and tenosynovitis | ultrasound scoring of synovitis and tenosynovitis | 24 weeks | 
| Level of biological markers | Level of biological markers and cell subpopulations (Interleukin, cytokines, immune cells) by result of blood test is evaluated. | 24 weeks | 
| Following of the quality of life | The Short Form 36 (SF36) is used to evaluate the quality of life. The SF36 scale includes 36 items divided into 8 dimensions (physical functioning, role limitations related to physical health, physical pain, general health, vitality [energy / fatigue]. | 36 weeks | 
| Following of the quality of life | The Hospital Anxiety and the Depression scale (HAD) is used to evaluate the quality of life. The HAD scale has 14 items rated from 0 to 3 with 7 questions relate to anxiety and 7 others to the depressive dimension. | 36 weeks | 
| Following of the quality of life | The scale EuroQol 5 dimensions (EDQ5) is used to evaluate the quality of life. The EQ-5D scale is a standardised measure of health status to provide a simple, generic measure of health for clinical and economic appraisal, whih is divided by the EQ-5D descriptive system (mobility, self care, usual activities, pain/discomfort, anxiety/depression) and the EQ Visual Analogue scale (EQ VAS). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems). | 36 weeks |