Abatacept in earLy Onset Polymyalgia Rheumatica: Study ALORS
Status:
Unknown status
Trial end date:
2020-09-07
Target enrollment:
Participant gender:
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.