NCT03576794: PMRLEFRCT

Treatment With Leflunomide in Patients With Polymyalgia Rheumatica

Status unknown Phase 3 Last updated 3 June 2019

What this trial tests

Phase 3 trial testing Leflunomide 20 mg in Polymyalgia Rheumatica in 94 participants. Status unknown.

Timeline

1 March 2019

Primary endpoint
1 November 2022

1 November 2022

Quick facts

Lead sponsor	Elisabeth Brouwer
Phase	Phase 3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	94
Start date	1 March 2019
Primary completion	1 November 2022
Estimated completion	1 November 2022
Sites	2 locations across Netherlands

Drugs / interventions tested

• Leflunomide 20 mg — full drug profile →
• Prednisolone — full drug profile →

Conditions studied

• Polymyalgia Rheumatica — all drugs for Polymyalgia Rheumatica →

Sponsor

Elisabeth Brouwer — full company profile →

Who can join

50 and older, any sex, with Polymyalgia Rheumatica. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Over the last decades outcome has greatly improved for rheumatoid arthritis (RA) and spondyloarthritis (SpA). This is in sharp contrast to the situation for polymyalgia rheumatica (PMR), with a lifetime prevalence of 2.4% for women and 1.7% for men, PMR is the commonest auto-inflammatory musculoskeletal disease in adults aged ≥50 years. Due to population ageing, the number of PMR patients will likely double in the decades to come (CBS). Glucocorticoids (GC) are the mainstay of treatment. However, there is an unmet medical need of alternatives in the treatment of PMR as 50% of patients will relapse or have difficulties to reduce the corticosteroid doses. Also, there is increasing awareness of steroid related toxicity and in addition, long-term toxicity is a well-known side-effect of glucocorticoids in PMR.

Low dose methotrexate (\< 10 mg per week) has been tested in two blinded randomized control trials and 4 open label studies and has shown low to moderate efficacy as corticosteroid-sparing agent. Studies on tumor necrosis factor (TNF) blockers yielded negative results. The effectiveness of leflunomide has only been convincingly demonstrated in case series.

The high rate of relapses and adverse events in steroid treated patients indicate that alternative adjuvant agents are needed.

There is evidence that leflunomide could serve as steroid sparing agent and that leflunomide can be used to prevent relapses in the clinical management of polymyalgia rheumatica.

We will perform a randomized placebo controlled trial. Eligible patients will be randomly assigned in a 1:1 ratio receiving either leflunomide 20 mg once daily + glucocorticoids , or placebo + glucocorticoids.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. PolyMyalgia Rheumatica treatment with Methotrexate in Optimal Dose in an Early disease phase (PMR MODE): study protocol for a multicenter double-blind placebo controlled trial.
   Marsman DE, Bolhuis TE, den Broeder N, den Broeder AA, et al · · 2022 · cited 12× · PMID 35428320 · DOI 10.1186/s13063-022-06263-3
2. Modern Management of Isolated Polymyalgia Rheumatica.
   Harkins P, Cowley S, Burke E, Harrington R, et al · · 2025 · PMID 41085890 · DOI 10.1007/s40744-025-00797-z