Article Text

other Versions

PDF
Deoxyspergualin in relapsing and refractory Wegener's granulomatosis
  1. Oliver Flossmann (oflossmann{at}doctors.org.uk)
  1. Addenbrooke's Hospital Cambridge, United Kingdom
    1. Bo Baslund (bbaslund{at}gmail.com)
    1. Dpt. or Rheumatology TA 4242, Rigshospitalet, Denmark
      1. Annette Bruchfeld (annette.bruchfeld{at}klinvet.ki.se)
      1. Department of Nephrology, Karolinska University Hospital at Huddinge, Stockholm, Sweden
        1. Jan W Cohen Tervaert (secretariaat-immuno{at}immuno.unimaas.nl)
        1. Academic Hospital Maastricht, Netherlands
          1. Catherine Hall (cathyh{at}holyrood.ed.ac.uk)
          1. Diseases Unit, Western General Hospital, Edinburgh, United Kingdom
            1. Peter Heinzel (pheinzel{at}enkgmbh.de)
            1. Euro Nippon Kayaku GmbH, Frankfurt/Main, Germany
              1. Bernhard Hellmich (b.hellmich{at}kk-es.de)
              1. Department of Rheumatology, University Hospital Schleswig-Holstein, Lübeck, Germany
                1. Raashid A Luqmani (raashid.luqmani{at}noc.anglox.nhs.uk)
                1. Nuffield Orthopaedic Centre, United Kingdom
                  1. Kyuichi Nemoto (kyuichi.nemoto{at}nipponkayaku.co.jp)
                  1. Euro Nippon Kayaku GmbH, Frankfurt/Main, Germany
                    1. Vladimir Tesar (tesarv{at}cesnet.cz)
                    1. Department of Nephrology, General Faculty Hospital, Prague, Czech Republic
                      1. David RW Jayne (dj106{at}cam.ac.uk)
                      1. Addenbrooke's Hospital, United Kingdom

                        Abstract

                        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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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.

                        Statistics from Altmetric.com

                        Request permissions

                        If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.