Justification And Evaluation of Baricitinib Plus Corticosteroids Versus corticosteroiDs Alone in pOlymyalgia RhEumatica

NCT07279688 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 29BRC23.0160 - JADORE-BARI
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 22

Brief Summary

Polymyalgia rheumatic (PMR) is an inflammatory rheumatic disease affecting the elderly. The diagnosis is based on established ACR/EULAR classification criteria. The activity of the disease is evaluated using the PMR-AS, a disease activity score based on morning stiffness, ability to elevate the upper limbs, physician's global disease assessment and pain assessment measured by the patient using VAS, and the C-reactive protein (CRP) level. The PMR-AS-CRP (PMR-AS) is considered as relevant to define disease activity (low activity \<7; moderate activity 7 to 17; high activity \>17), flare (\>10), remission (\<1.5), but also to decide if treatment has to be decreased, unchanged or increased (PMR-AS \<10: decrease, PMR-AS \>20 increase, 10≤ PMR-AS ≤20: stable dose) \[10-12\]. Long term low-dose glucocorticoid (GCs) (prednisone or prednisolone started at 12.5 to 25 mg/day progressively tapered) is the mainstay of the treatment. But comorbidities in PMR are due to GCs and 30% of the patients underwent a relapse when tapering GCs. Today, the physicians do not know what is the best duration and the best dosage of GCs. The international recommendation suggests to start prednisone at a dose between 12.5 to 25 mg, to be at 10 mg at 1 or 2 months, and then to decrease slowly. The treatment is generally ordered for 6-18 months but it is possible to try a shorter treatment duration when patients have been previously treated with GCs or in case of comorbidities. The TENOR study, a phase 2 study, demonstrated efficacy of tocilizumab as first line treatment in PMR and its ability to spare GCs. The Semaphore study confirmed the usefulness of tocilizumab in corticodependent forms and demonstrated its efficacy. Another IL-6 inhibitor, sarilumab was authorized for the treatment for polymyalgia rheumatic in adult patients with inadequate response to corticosteroid or relapsing disease but is not reimbursed in France. Baricitinib is an oral selective JAK inhibitor of JAK1 and JAK2 with a short half-life. There are two dosages available (i.e., 2-mg and 4-mg) which can help conduct a simple dose tapering. Administration of baricitinib resulted in a rapid dose dependent inhibition of IL-6 induced STAT3 phosphorylation. An evaluation could be made using the PMR-AS with and without imputation to minimize the effect of baricitinib on CRP by anti-IL-6 effect. Preliminary results of the BACHELOR study (34 patients treated with baricitinib or placebo) suggested a great efficacy of baricitinib in early PMR without steroids. It could be a treatment of PMR, with low dose or no steroids only during the first month, to minimize the adverse events of steroids. JAK inhibitors have been reevaluated by EMA, the Oral Surveillance study suggesting that tofacitinib (Xeljanz®) increases the risk of major cardiovascular problems, cancer, VTE, serious infections and death due to any cause when compared with medicines belonging to the class of TNF-alpha inhibitors. EMA has concluded that these safety findings apply to all approved uses of JAK inhibitors in chronic inflammatory disorders. Nevertheless, the risk was not increased during the first months of treatment in all studies and a short treatment could have lower risks than steroids. As no suitable treatment alternatives are available, excepted GCs which increase the vascular risk and osteoporosis, short treatment by jak inhibitor could be a relevant alternative treatment of PMR. Indeed, the physicians do not have any disease modifying drug (excepted anti IL6 off-label) in treatment of PMR. So, GCs are used for more than one year in the treatment of PMR. Baricitinib, used only 6 months demonstrated its ability to cure early PMR without steroids. It could be an alternative to steroid when physicians consider that ratio benefit/risk is better with a 6 months treatment by baricitininib than \>one year by steroids. Our goal is now to demonstrate in a large cohort the ability of a 6-month treatment with baricitinib in comparison to placebo to decrease glucocorticoids and then to maintain low disease activity without corticosteroids in PMR and a good safety profile. Due to the possible lower risk of 2 mg than 4 mg of baricitinib, but probably a lower efficacy, the investigators plan to compare both baricitinib (4 mg and 2 mg) to placebo. The study will be conducted in France.

Conditions

Polymyalgia Rheumatica (PMR)

Outcome Measures

Primary Outcomes (1)

• Following of the Polymyalgia Rheumatica Activity score

  Polymyalgia Rheumatica Activity Score (PMR-AS) ≤10 (no flare) without steroids at week 24. The Polymyalgia Rheumatica Activity Score is calculated by combining several parameters (patient's pain assessment (using a visual analogue scale) + physician's global assessment of the disease (using a visual analogue scale)+ morning stiffness + C-Reactive Protein level). If PMR-AS ≤ 1,5 means remission of the disease. If PMR-AS \< 7 means inactive activity of the disease. If 7 \<PMR-AS \< 17 means low activity of the disease. If PMR-AS \> 17 means high activity of the disease.

  From week 0 to week 24

Secondary Outcomes (3)

• Following of the Polymyalgia Rheumatica Activity score

  From week 0 to week 12

• Following of the Polymyalgia Rheumatica Activity score

  From week 0 to week 36

• Following of the Polymyalgia Rheumatica Activity score

  From week 0 to week 36

Study Arms (3)

Experimental group 4 mg

ACTIVE COMPARATOR

Oral baricitinib 4 mg for 12 weeks; Oral GCs prescribed at baseline Then, at week 12, if PMR-AS ≤10, patients will receive baricitinib 4 mg for 12 weeks. If PMR-AS \>10, they will receive GCs according to the PMR-AS. 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 4 MG Oral Tablet; Drug: Placebo 2 mg

Experimental group 2 mg

ACTIVE COMPARATOR

Oral baricitinib 2 mg for 12 weeks; Oral GCs prescribed at inclusion Then, at week 12, if PMR-AS ≤10, patients will receive baricitinib 2 mg for 12 weeks. If PMR-AS \>10, they will receive GCs according to the PMR-AS. 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 2 MG Oral Tablet; Drug: Placebo 4 mg

Control group

PLACEBO COMPARATOR

Oral placebo for 12 weeks; Oral GCs at inclusion. Then, at week 12, if PMR-AS ≤10, placebo for 12 weeks. If PMR-AS \>10, they will receive GCs according to the PMR-AS. 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) and according to investigator's opinion.

Drug: Placebo 4 mg; Drug: Placebo 2 mg

Interventions

Baricitinib 4 MG Oral Tablet DRUG

Patient will take a tablet of 4 mg/d during 12 weeks and then 4 mg/d during 12 weeks if the patient achieves PMR-AS≤ 10 at week 12.

Experimental group 4 mg

Baricitinib 2 MG Oral Tablet DRUG

Patient will take a tablet of 2 mg/d during 12 weeks and then 2 mg/d during 12 weeks if the patient achieves PMR-AS≤ 10 at week 12.

Experimental group 2 mg

Placebo 4 mg DRUG

Patient will take a tablet of placebo for 12 weeks and then placebo during 12 weeks if the patient achieves PMR-AS ≤ 10 at week 12.

Control group; Experimental group 2 mg

Placebo 2 mg DRUG

Patient will take a tablet of placebo for 12 weeks and then placebo during 12 weeks if the patient achieves PMR-AS ≤ 10 at week 12.

Control group; Experimental group 4 mg

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 50 years of age.
• Fulfilling ACR/EULAR classification criteria for PMR newly diagnosed or treatment resistant.
• No GCs or GCs \<15 mg/day since at least 15 days prior to planned randomization.
• PMR-AS-CRP \>17.
• Absence of other inflammatory arthropathy, connective tissue diseases or vasculitis.
• Able to give informed consent.
• French health insurance holder

You may not qualify if:

• Clinical evidence of giant cell arteritis.
• Uncontrolled high blood pressure or cardiovascular disease.
• High risk of VTE because of a history of VTE (DVT and/or PE) within 12 weeks prior to randomization or a history of recurrent (\>1) VTE (counting co-occurring DVT+PE as 1 single event).
• Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to PMR
• Current smoker if age \>65 years.
• Current active uncontrolled infection.
• Treatment by probenecid.
• Alkaline phosphatase (ALP) ≥2 x ULN.
• Total bilirubin level (TBL) ≥1.5 x ULN.
• Neutropenia (absolute neutrophil count \<1000 cells/uL) (\<1.00 x 103/uL or \<1.00 GI/L).
• Lymphopenia (lymphocyte count \<500 cells/uL) (\<0.50 x 103/uL or \<0.50 GI/L).
• Patient under court protection or protected adults

Sponsors & Collaborators

• University Hospital, Brest: lead
• Eli Lilly and Company: collaborator

Study Sites (22)

VIDAL François

Aix-en-Provence, France

Location

LEGRAND Jean-Louis

Arras, France

Location

Besançon-CIC

Besançon, 25000, France

Location

PRATI Clément

Besançon, France

Location

CHU de Bordeaux Pellegrin

Bordeaux, 33076, France

Location

Dr Alain SARAUX

Brest, France

Location

RAT Anne-Christine

Caen, France

Location

LESKE Charles

Cholet, France

Location

TOURNADRE Anne

Clermont-Ferrand, France

Location

RAMON André

Dijon, France

Location

APHP - Kremlin-Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

DIREZ Guillaume

Le Mans, France

Location

FLIPO René-Marc

Lille, France

Location

WIRTH Théo

Marseille, France

Location

LE HENAFF Catherine

Morlaix, France

Location

CHU de Nice

Nice, 06000, France

Location

FAUTREL Bruno - AP-HP La Pitié-Salpétrière

Paris, France

Location

OTTAVIANI Sébastien - AP-HP Bichat

Paris, France

Location

CHU Reims

Reims, France

Location

GOTTENBERG Jacques-Eric

Strasbourg, France

Location

CHU de Toulouse

Toulouse, 31059, France

Location

CARVAJAL ALEGRIA Guillermo

Tours, France

Location

MeSH Terms

Conditions

Polymyalgia Rheumatica

Interventions

baricitinib; Tablets

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Alain SARAUX, Pr

CONTACT

+33298223333; alain.saraux@chu-brest.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicentre double blinded randomized (1:1:1 ratio) placebo-controlled trial.

Study Record Dates

• First Submitted: November 28, 2025
• First Posted: December 12, 2025
• Study Start: December 12, 2025
• Primary Completion (Estimated): November 12, 2028
• Study Completion (Estimated): June 12, 2029
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

FR (22)