Treatment With Leflunomide in Patients With Polymyalgia Rheumatica

Summary

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.

Conditions

• Polymyalgia Rheumatica

Interventions

DRUG

Leflunomide 20 mg

During the first 2 weeks after randomization patients will receive Leflunomide 20 mg every other day. After 2 weeks Leflunomide will be increased to 20 mg once daily and this therapy will be continued during 12 months.

DRUG

Prednisolone

Patients in both groups will receive prednisolone 15 mg once daily and will be randomized within 4 weeks of the start of glucocorticoid therapy (prednisolone). Prednisolon will be tapered according to a short fixed protocol with a slow gradual taper till 0 in week 27.

Sponsors & Collaborators

• Dutch Arthritis Foundation Reuma Nederland

  collaborator UNKNOWN

• Elisabeth Brouwer

  lead OTHER

Principal Investigators

• Elisabeth Brouwer · University Medical Center Groningen

• E.M. Colin · ZGT Almelo

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-03-01

Primary Completion

2022-11-01

Completion

2022-11-01

Countries

• Netherlands

Study Locations