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Safety and efficacy of Leflunomide in primary Sjögren’s syndrome - A phase II pilot study
  1. JM van Woerkom (vanwoerkom{at}
  1. Gelre Ziekenhuizen Apeldoorn, Netherlands
    1. A A. Kruize (a.kruize{at}
    1. University Medical Center Utrecht, Netherlands
      1. R Geenen (r.geenen{at}
      1. Department of Health Psychology, Utrecht University, Netherlands
        1. E N van Roon (e.roon3{at}
        1. Dept of Pharmacology, Medical Center Leeuwarden, Netherlands
          1. R Goldschmeding (r.goldschmeding{at}
          1. Dept of Pathology, UMC Utrecht, Netherlands
            1. S MM Verstappen (s.verstappen{at}
            1. University Medical Center Utrecht, Netherlands
              1. J AG van Roon (j.vanroon{at}
              1. University Medical Center Utrecht, Netherlands
                1. J WJ Bijlsma (j.w.j.bijlsma{at}
                1. University Medical Center Utrecht, Netherlands


                  Objectives:For invalidating symptoms in primary Sjögren’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.

                  • Leflunomide
                  • efficacy
                  • primary Sjögren’s syndrome
                  • safety
                  • treatment

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