Safety and efficacy of Leflunomide in primary Sjogren's syndrome - A phase II pilot study.

Author(s): van Woerkom J, Kruize AA, Geenen R, van Roon EN, Goldschmeding R, Verstappen SM, van Roon JA, Bijlsma JW

Affiliation(s): Gelre Ziekenhuizen Apeldoorn, Netherlands.

Publication date & source: 2007-01-12, Ann Rheum Dis., [Epub ahead of print]

Publication type:

OBJECTIVES: For invalidating symptoms in primary Sjogren's syndrome (pSS), a need remains for easy-to- administer, (cost)-effective and well-tolerated systemic therapy. Leflunomide (LEF) is structurally unrelated to other immunomodulatory drugs and might be efficacious in pSS, given its characteristic immunoregulatory modes of action. We performed a phase II open label pilot study to investigate the safety and efficacy of LEF in pSS. METHODS: Fifteen pSS patients with early and active disease received LEF 20 mg once daily for 24 weeks. Tolerability, safety and efficacy of LEF were evaluated every 8 weeks. Additional safety visits were performed fortnightly. RESULTS: Mild gastro-intestinal discomfort (including diarrhoea) and hair loss were reported mostly. Five patients developed lupus-like skin lesions on face, arms or trunk, responding well to topical corticosteroids, nevertheless causing withdrawal of 1 patient. Two patients with pre-existing hypertension had to increase dosages of anti-hypertensive drugs. Elevated alanine aminotransferase levels normalized after dose reduction in 2 patients. A decrease in general fatigue and increase in physical functioning were observed after 24 weeks. Serum IgG decreased from 8 weeks onwards. Schirmer test values increased not reaching statistically significance whereas sialometry values did not change. In 4 of 5 repeated biopsies, the lymphocytic focus score decreased with 1 focus/4 mm2. A remarkable amelioration of leucocytoclastic vasculitis was observed in 3 patients. CONCLUSIONS: Although the safety profile seems fairly acceptable, the observed indications for efficacy were modest and may provide doubt on justifying a randomized controlled trial of LEF in pSS.