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Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study
  1. Eric Hachulla1,
  2. Pierre-Yves Hatron1,
  3. Patrick Carpentier2,
  4. Christian Agard3,
  5. Emmanuel Chatelus4,
  6. Patrick Jego5,
  7. Luc Mouthon6,
  8. Viviane Queyrel7,
  9. Anne-Laure Fauchais8,
  10. Ulrique Michon-Pasturel9,
  11. Roland Jaussaud10,
  12. Alexis Mathian11,
  13. Brigitte Granel12,
  14. Elisabeth Diot13,
  15. Dominique Farge-Bancel14,
  16. Arsène Mekinian15,
  17. Jérôme Avouac16,
  18. Hélène Desmurs-Clavel17,
  19. Pierre Clerson18
  20. on behalf of the SEDUCE study group
    1. 1Médecine Interne, Hopital Huriez, Université de Lille, Lille, France
    2. 2Médecine Vasculaire, CHU, Grenoble, France
    3. 3Médecine Interne, Hôpital Hôtel Dieu, Nantes, France
    4. 4Rhumatologie, Hôpital Hautepierre, Strasbourg, France
    5. 5Médecine Interne, CHR Rennes Sud, Rennes, France
    6. 6Médecine Interne, AP-HP, Hôpital Cochin, Université Paris Descartes, Paris, France
    7. 7Médecine Interne, Hôpital de l'Archet 1, Nice, France
    8. 8Médecine Interne, Hôpital Dupuytren, Limoges, France
    9. 9Médecine Vasculaire, Hôpital Saint Joseph, Paris, France
    10. 10Médecine Interne, Hôpital Robert Debré, Reims, France
    11. 11Médecine Interne 2, Hôpital Pitié-Salpêtrière, Paris, France
    12. 12Médecine Interne, Hôpital Nord, Aix Marseille Université, Marseille, France
    13. 13Médecine Interne, Hôpital Bretonneau, Tours, France
    14. 14Médecine Interne, Hôpital Saint Louis, Paris, France
    15. 15Medicine interne and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), AP-HP, Hôpital Saint Antoine, Paris, France
    16. 16Rhumatologie A, Hôpital Cochin, Paris, France
    17. 17Médecine Interne, Hôpital Edouard Herriot, Lyon, France
    18. 18Orgamétrie Biostatistiques, Roubaix, France
    1. Correspondence to Professor Eric Hachulla, Scleroderma National Centre, Department of Internal Medicine, Université de Lille, Hôpital Huriez, Place de Verdun, Lille cedex 59037, France; ehachullla{at}chru-lille.fr

    Abstract

    Objective To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc).

    Methods Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05).

    Results Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12).

    Conclusions The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit.

    Trial registration number NCT01295736.

    • Autoimmune Diseases
    • Patient perspective
    • Treatment

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