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Deoxyspergualin in relapsing and refractory Wegener's granulomatosis
  1. Oliver Flossmann (oflossmann{at}
  1. Addenbrooke's Hospital Cambridge, United Kingdom
    1. Bo Baslund (bbaslund{at}
    1. Dpt. or Rheumatology TA 4242, Rigshospitalet, Denmark
      1. Annette Bruchfeld (annette.bruchfeld{at}
      1. Department of Nephrology, Karolinska University Hospital at Huddinge, Stockholm, Sweden
        1. Jan W Cohen Tervaert (secretariaat-immuno{at}
        1. Academic Hospital Maastricht, Netherlands
          1. Catherine Hall (cathyh{at}
          1. Diseases Unit, Western General Hospital, Edinburgh, United Kingdom
            1. Peter Heinzel (pheinzel{at}
            1. Euro Nippon Kayaku GmbH, Frankfurt/Main, Germany
              1. Bernhard Hellmich (b.hellmich{at}
              1. Department of Rheumatology, University Hospital Schleswig-Holstein, Lübeck, Germany
                1. Raashid A Luqmani (raashid.luqmani{at}
                1. Nuffield Orthopaedic Centre, United Kingdom
                  1. Kyuichi Nemoto (kyuichi.nemoto{at}
                  1. Euro Nippon Kayaku GmbH, Frankfurt/Main, Germany
                    1. Vladimir Tesar (tesarv{at}
                    1. Department of Nephrology, General Faculty Hospital, Prague, Czech Republic
                      1. David RW Jayne (dj106{at}
                      1. Addenbrooke's Hospital, United Kingdom


                        Objectives: Conventional therapy of Wegener’s granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. The efficacy and safety of an alternative immunosuppressive drug, deoxyspergualin, was evaluated in patients with relapsing or refractory disease.

                        Methods: A prospective, international, multi-centre, single limb, open label study. Entry required active Wegener’s granulomatosis with a Birmingham Vasculitis Activity Score (BVAS) ≥4 and previous therapy with cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status. Deoxyspergualin, 0.5mg/kg/day, was self-administered by subcutaneous injection in six cycles of 21 days with a seven day washout between cycles. Cycles were stopped early for white blood count < 4,000/mm3. The primary endpoint was complete remission (BVAS=0 for at least 2 months) or partial remission (BVAS<50% of entry score). After the sixth cycle azathioprine was commenced and follow-up continued for six months.

                        Results: 42/44 patients (95%) achieved at least partial remission and 20/44 (45%) achieved complete remission. BVAS fell from 12 (4-25), median, range; at baseline to 2 (0-14) at the end of study (p<0.001). Prednisolone doses were reduced from 20 to 8mg/day (p<0.001). Relapses occurred in 18 (43%) patients after a median of 170 (44-316) days after achieving remission. Severe or life-threatening (≥ grade 3) treatment-related adverse events occurred in 24 (53%) patients mostly due to leukopaenias.

                        Conclusions: Deoxyspergualin achieved a high rate of disease remission and permitted prednisolone reduction in refractory or relapsing Wegener’s granulomatosis. Adverse events were common but rarely lead to treatment discontinuation.

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