Xavier Puéchal1, Christian Pagnoux1, Gabriel Baron2, Thomas Quémeneur3, Antoine Néel4, Christian Agard4, François Lifermann5, Eric Liozon6, Marc Ruivard7, Pascal Godmer8, Nicolas Limal9, Arsène Mékinian10, Thomas Papo11, Anne-Marie Ruppert12, Anne Bourgarit13, Boris Bienvenu14, Loïck Geffray15, Jean-Luc Saraux16, Elisabeth Diot17, Bruno Crestani11, Xavier Delbrel18, Laurent Sailler19, Pascal Cohen1, Véronique Le Guern1, Benjamin Terrier1, Matthieu Groh1, Claire Le Jeunne1, Luc Mouthon1, Philippe Ravaud2, Loïc Guillevin1. 1. National Referral Center for Rare Systemic and Autoimmune Diseases, Department of Internal Medicine, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France. 2. Université Paris Descartes, Hôtel-Dieu, AP-HP, Paris, France. 3. Centre Hospitalier, Valenciennes, France. 4. Centre Hospitalier Universitaire Hôtel-Dieu, Nantes, France. 5. Centre Hospitalier Côte d'Argent, Dax, France. 6. Centre Hospitalier Universitaire Dupuytren, Limoges, France. 7. Centre Hospitalier Universitaire Estaing, Clermont-Ferrand, France. 8. Centre Hospitalier Bretagne Atlantique, Vannes, France. 9. Hôpital Henri-Mondor, Université Paris-Est Créteil, AP-HP, Créteil, France. 10. Hôpital Saint-Antoine, Université Pierre et Marie Curie, AP-HP, Paris, France. 11. Hôpital Bichat-Claude-Bernard, Université Denis-Diderot, AP-HP, Paris, France. 12. Hôpital Tenon, Université Pierre et Marie Curie, AP-HP, Paris, France. 13. Hôpital Jean-Verdier, Université Léonard-de-Vinci, AP-HP, Bondy, France. 14. Centre Hospitalier Universitaire Côte de Nacre, Caen, France. 15. Centre Hospitalier, Lisieux, France. 16. Centre Hospitalier Simone-Veil, Eaubonne, France. 17. Centre Hospitalier Universitaire, Tours, France. 18. Centre Hospitalier, Pau, France. 19. Centre Hospitalier Universitaire Purpan, Toulouse, France.
Abstract
OBJECTIVE: In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). METHODS: All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. RESULTS:Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. CONCLUSION: Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.
RCT Entities:
OBJECTIVE: In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). METHODS: All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. RESULTS: Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPApatients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. CONCLUSION: Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPAasthma/rhinosinusitis exacerbation rate.
Authors: Jonathan Steinfeld; Eric S Bradford; Judith Brown; Stephen Mallett; Steven W Yancey; Praveen Akuthota; Maria C Cid; Gerald J Gleich; David Jayne; Paneez Khoury; Carol A Langford; Peter A Merkel; Frank Moosig; Ulrich Specks; Peter F Weller; Michael E Wechsler Journal: J Allergy Clin Immunol Date: 2018-12-19 Impact factor: 10.793