Treatment With Leflunomide in Patients With Polymyalgia Rheumatica

• Status: Recruiting
• Trial end date: 2022-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Elisabeth Brouwer
• Collaborators: Dutch Arthritis Foundation Reuma Nederland; Reumafonds
• Treatments: Glucocorticoids; Leflunomide; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

Inclusion Criteria:

1. Signed written informed consent

2. Female or male aged ≥ 50 years

3. PMR according to the American College of Rheumatology (ACR)/European league Against Rheumatism (EULAR) 2012 PMR core (essential) classification criteria

4. Newly diagnosed PMR being on glucocorticoids for less than 4 weeks

Exclusion Criteria:

1. Presence of any other connective tissue disease, including vasculitis/giant-cell arteritis

2. PMR on glucocorticoids for >4 week or >25 mg/day

3. History of alcohol or drug abuse or current alcohol or drug abuse

4. Transplanted organ (except corneal transplant performed more than 3 months prior to screening)

5. Evidence (as assessed by the investigator) of active infection, presence of hepatitis B surface antigen or hepatitis C antibody in blood, HIV positivity.

6. Malignancy within 5 years prior to screening, except for non-melanoma skin cancer

7. Exposure to DMARD/biological in the last 5 years

8. Pain syndromes, e.g. fibromyalgia, drug-induced myalgia

9. Active thyroid disease

10. Neurological diseases, e.g. Parkinson's disease

11. Contraindications for Leflunomide (serious immunodeficiency, e.g. AIDS, cytopenia as defined under 12, moderate to severe kidney failure (as defined under 12), liver test abnormality (as defined under 12)

12. Laboratory abnormalities:

• Glomerular filtration rate <50 ml/min

• Alanine-aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5x upper limit of normal

• Platelet count <100 x 109/L (100,000/mm3)

• Hemoglobin <85 g/L (8.5 g/dL; 5.3 mmol/L)

• White blood cells <3.0 x 109/L (3,000/mm3)Absolute neutrophil count <2.0 x 109/L (2,000/mm3)

• Absolute lymphocyte count <0.5 x 109/L (500/mm3)

13. Uncontrolled or poorly controlled hypertension

14. Major surgery or hospitalization within 3 month prior to screening

15. Any medical condition that could interfere with the implementation or interpretation of the study or with the safety of the patient during the study.