Abatacept in earLy Onset Polymyalgia Rheumatica: Study ALORS

NCT03632187 | Completed Phase 3 DMC

• 1 other identifier: 29BRC17.0228 _ALORS
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 5

Brief Summary

Polymyalgia rheumatic (PMR) is a frequent inflammatory disease. It affects the elderly, with peak incidences at the age of 70 to 80 years; an age \>50 years or older, is considered a criterion for the diagnosis. Polymyalgia rheumatica occurs at a frequency that is 3 to 10 times that of giant-cell arteritis. Disease risk varies according to race and geographic region. The incidence is highest among whites in northern European populations (about 20 cases per 100,000 persons older than 50 years of age); it is lower in southern European populations (about 10 cases per 100,000).The diagnosis is based on established ACR/EULAR classification criteria. Long term low-dose glucocorticoid (GCs) (prednisone or prednisolone started at 15 to 20 mg/day progressively tapered) is the mainstay of the treatment. The activity of PMR 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 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).. Comorbidity in PMR are due to GCs and 30% of the patients underwent a relapse when tapering GCs. If the investigators able to start prednisone at a lower dosage (i.e. 8 mg then tapered for 3 to 4 months), the cumulative dosage of steroid would not have major side effects but it is not possible without new therapeutic agents. The TENOR study (Tolerance and Efficacy of tocilizumab iN pOlymyalgia Rheumatica), a phase 2 study, demonstrated efficacy of tocilizumab as first line treatment in PMR without GCs and its ability to spare GCs. This was the first study demonstrating that a biologic may improve PMR without steroid, and that also showed that a short treatment by biologic followed by a low dose GCs therapy may be a new concept in the treatment of PMR. Molecular studies in GCA and PMR suggest that dendritic cells initiate the pathogenic cascade and recruit T cells. Two major immune-response networks have been identified related to type 1 helper T-cell (Th1) and to helper T-cell (Th17). Abatacept is comprised of the ligand-binding domain of CTLA4 plus modified Fc domain derived from IgG1. By containing CTLA4, abatacept blocks the engagement of CD28 with its ligand, thereby inhibiting T cell activation. It has recently demonstrated its efficacy in Granulomatosis with polyangiitis (GPA) but also in giant cell arteritis (GCA). Due to its good safety profile in rheumatoid arthritis and its potential to modulate T cell activation and derived cytokines, abatacept is an attractive agent to investigate in patients with PMR. In this randomized prospective placebo controlled study, the objective is to demonstrate the ability of abatacept to improve alone PMR and then to allow a steroid sparing effect after this induction treatment, in early onset PMR.

Conditions

Polymyalgia Rheumatica

Outcome Measures

Primary Outcomes (1)

• Following of one biological parameter (CRP)

  The Polymyalgia Rheumatica Activity score is evaluated with a biological parameter named CRP.

  12 weeks

Secondary Outcomes (12)

• Emergence of adverse events (Safety and tolerability)

  36 weeks

• Following of the Polymyalgia Rheumatica Activity score

  36 weeks

• Medical resource evaluation

  36 weeks

• Following of the cumulative dosages of Glucocorticoids

  24 weeks

• The flare of the Polymyalgia Rheumatica

  36 weeks

Study Arms (2)

Experimental group

EXPERIMENTAL

Subcutaneous abatacept every weeks during 3 months (W0 to W11). Then, at W12, 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). Dosage of GCs will be decreased between W16 and W24 (1mg every week) in each arm according to PMR-AS (PMR-AS \< 10: decrease, PMR-AS \> 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose). If PMR-AS ≤10, the patients wont receive any treatment until a flare.

Drug: Abatacept

Control group

PLACEBO COMPARATOR

Subcutaneous placebo every week during 3 months (W0 to W11). Then, at week 12, 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). Dosage of GCs will be decreased between W16 and W24 (1mg every week) in each arm according to PMR-AS (PMR-AS \< 10: decrease, PMR-AS \> 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose). If PMR-AS ≤10, the patients won't receive any treatment until a flare.

Drug: Placebos

Interventions

Abatacept DRUG

Subcutaneous abatacept every weeks during 3 months

Experimental group

Placebos DRUG

Subcutaneous placebo every week during 3 months

Control group

Eligibility Criteria

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

You may qualify if:

• Age older than 50 years
• Fulfilling ACR/EULAR criteria
• Disease duration≤6 months
• No steroid since 2 weeks prior randomization
• PMR-AS≥ 17
• Absence of signs or symptoms of other musculoskeletal or connective tissue conditions
• Able to give informed consent
• Concomitant treatments with methotrexate or hydroxychloroquine are not permitted.

You may not qualify if:

• 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
• History of malignant neoplasm within the last 5 years.
• Current active infection not controlled

Sponsors & Collaborators

• University Hospital, Brest: lead
• Bristol-Myers Squibb: collaborator

Study Sites (5)

CHRU de Brest

Brest, France, 29609, France

Location

CH Le Mans

Le Mans, France

Location

CH de Morlaix

Morlaix, France

Location

CH St-Malo

St-Malo, France

Location

CHU Strasbourg

Strasbourg, France

Location

Related Publications (2)

• Saraux A, Le Henaff C, Dernis E, Carvajal-Alegria G, Tison A, Quere B, Petit H, Felten R, Jousse-Joulin S, Guellec D, Marhadour T, Kervarrec P, Cornec D, Querellou S, Nowak E, Souki A, Devauchelle-Pensec V. Abatacept in early polymyalgia rheumatica (ALORS): a proof-of-concept, randomised, placebo-controlled, parallel-group trial. Lancet Rheumatol. 2023 Dec;5(12):e728-e735. doi: 10.1016/S2665-9913(23)00246-1.

  PMID: 38251563 DERIVED

• Allard B, Devauchelle-Pensec V, Saraux A, Nowak E, Tison A, Boukhlal S, Guellec D, Jousse-Joulin S, Cornec D, Marhadour T, Le Pennec R, Salaun PY, Querellou S. [18F]FDG PET/CT for therapeutic assessment of Abatacept in early-onset polymyalgia rheumatica. Eur J Nucl Med Mol Imaging. 2024 Apr;51(5):1297-1309. doi: 10.1007/s00259-023-06557-x. Epub 2023 Dec 14.

  PMID: 38095675 DERIVED

MeSH Terms

Conditions

Polymyalgia Rheumatica

Interventions

Abatacept

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Design

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

Model Details: This is a multicenter double blinded randomized placebo controlled trial

Study Record Dates

• First Submitted: July 11, 2018
• First Posted: August 15, 2018
• Study Start: December 13, 2018
• Primary Completion: October 21, 2021
• Study Completion: June 23, 2022
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)