0725: Real-life Use of the PEXIVAS Reduced-dose Glucocorticoid Regimen in Granulomatosis with Polyangiitis and Microscopic Polyangiitis

Sophie Nagle¹, Yann Nguyen², Xavier Puéchal³, Dimitri Titeca-Beauport⁴, Thomas Crépin⁵, Rafik Mesbah⁶, Idris Boudhabhay⁷, Gregory Pugnet⁸, Juliette Woessner⁹, Roderau Outh¹⁰, Céline Lebas¹¹, Antoine Néel¹², alexandre Karras¹³, Eric Hachulla¹¹, Benjamin Subran¹⁴, Philippe Kerschen¹⁵, Mathieu Gerfaud-Valentin¹⁶, Stéphane Vinzio¹⁷, Tiphaine Goulenok¹⁸, Raphael Borie¹⁹, Sébastien Humbert²⁰, Yurdagul Uzunhan²¹, Sarah Melboucy-Belkhir²², Jean-Baptiste Gouin²³, Mary-Jane Guerry²⁴ and Benjamin Terrier²⁵, ¹AP-HP Cochin Hospital, Paris, France, ²Department of Internal Medicine, Hôpital Beaujon, AP-HP, Clichy, France., Montmorency, France, ³National Referral Center for Rare Systemic Autoimmune Diseases, Paris, France, ⁴CHU Amiens, Amiens, France, ⁵Amiens University Hospital, Amiens, France, ⁶Boulogne Hospital (CH), Boulogne, France, ⁷Necker University Hospital, Paris, France, ⁸CHU Toulouse Rangueil Service de Medecine Interne et Immunologie Clinique, Toulouse, France, ⁹Avignon Hospital (CH), Avignon, France, ¹⁰Perpignan Hospital (CH), Perpignan, France, ¹¹Lille University Hospital, Lille, France, ¹²CHU Nantes, Nantes, France, ¹³HEGP - APHP, Paris, France, ¹⁴Croix Saint Simon Hospital, Paris, France, ¹⁵Department of Neurology, Luxembourg Hospital Center, Luxembourg City, Luxembourg, ¹⁶Lyon University Hospital, Lyon, France, ¹⁷Grenoble Hospital (CH), Grenoble, France, ¹⁸Assistance Publique Hopitaux de Paris, Paris, France, ¹⁹Bichat-Claude Bernard, Universite de Paris, Paris, France, ²⁰Besançon University Hospital, Besançon, France, ²¹AP-HP, Bobigny, France, ²²Saint Quentin Hospital, Saint-Quentin, France, ²³Vannes Hospital (CH Bretagne Atlantique), Vannes, France, ²⁴Valenciennes Hospital (CH), Valenciennes, France, ²⁵Department of Internal Medicine, Hôpital Cochin, AP-HP, Paris, France

Background/Purpose: Glucocorticoids (GCs) in combination with rituximab (RTX) or cyclophosphamide are the cornerstone of treatment for patients with severe granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). GCs are associated with adverse effects, including serious infections. The PEXIVAS trial demonstrated non-inferiority of reduced-dose GC regimen compared to standard dose for the incidence of death or end-stage kidney disease (ESKD), with a significant reduction in serious infections at one year. However, the primary endpoint did not include disease progression or relapse, the majority of patients received cyclophosphamide as induction therapy, and subgroup analysis showed a trend towards an increased risk of death or ESKD in RTX-treated patients. We aimed to evaluate the efficacy and safety of the reduced-dose GC regimen in a real-world setting.

Methods: We conducted a retrospective, multicentre study comparing the PEXIVAS reduced-dose GC regimen with a standard regimen in patients with severe GPA or PAM flare between January 2018 and April 2022. The primary composite endpoint included the occurrence of death, ESKD, progression before remission requiring treatment modification or relapse, whichever occurred first. Factors associated with the occurrence of the primary endpoint and of death or ESKD (i.e. the PEXIVAS endpoint) were estimated using univariate and multivariate Cox models. In a sensitivity analysis, patients treated with reduced-dose and standard-dose GCs were compared after matching on a propensity score.

Results: Of the 234 patients enrolled (93 MPA and 148 GPA), 126 (53.8%) received a reduced GC regimen and 108 (46.2%) received a standard regimen. The primary endpoint occurred in 62/234 (26.5%) of patients during the first year of follow-up: 33.3% of patients on the reduced dose versus 18.5% on the standard dose (p=0.016).

In multivariate analysis, a reduced GC regimen was significantly associated with the occurrence of the endpoint compared to a standard regimen (HR 1.72; 95%CI 1.08-2.74) (Figure 1), but was not associated with an increased risk of death or ESKD (HR 1.62; 95%CI 0.82-3.19) (Figure 2). There was no significant difference in serious infections at 1 year (20.6% vs 15.7%, p=0.427).

After propensity score matching, the reduced-dose GC regimen tended to be more likely to meet the primary endpoint than the standard regimen (HR 1.57; 95%CI 0.93-2.64) (Figure 3). In the subgroup of patients treated with the reduced-dose GC regimen, patients with creatinine levels above 300 μmol/L were more likely to meet the primary endpoint (RR 2.14; 95% CI 1.14-4.03). Similarly, in the subgroup of patients treated with RTX, the reduced-dose GC regimen tended to be more likely to achieve the primary endpoint (HR 1.61; 95% CI 0.94-2.77) and was more likely to meet death or ESKD (HR 2.42; 95%CI 1.04-5.66).

Conclusion: In patients with severe GPA or MPA, the reduced-dose GC regimen was associated with an increased risk of death, ESKD, progression before remission requiring treatment modification or relapse. This risk was even greater in patients with creatinine levels above 300 μmol/L and in those treated with RTX as induction therapy.








S. Nagle: None; Y. Nguyen: None; X. Puéchal: None; D. Titeca-Beauport: None; T. Crépin: None; R. Mesbah: None; I. Boudhabhay: None; G. Pugnet: None; J. Woessner: None; R. Outh: None; C. Lebas: None; A. Néel: None; a. Karras: AstraZeneca, 6, GlaxoSmithKlein(GSK), 4, Novartis, 2, Pfizer, 6; E. Hachulla: None; B. Subran: None; P. Kerschen: None; M. Gerfaud-Valentin: None; S. Vinzio: None; T. Goulenok: None; R. Borie: None; S. Humbert: None; Y. Uzunhan: None; S. Melboucy-Belkhir: None; J. Gouin: None; M. Guerry: None; B. Terrier: AstraZeneca, 5, CSL Vifor, 2, GlaxoSmithKlein(GSK), 2.