Glutathione S Transferases (GST) Polymorphisms Are Independents Predictors of Efficacy and Toxicity in Lupus Nephritis Treated with Cyclophosphamide

Alexandra Audemard-Verger¹, Nicolas Martin Silva², Céline Verstuyft³, Nathalie Costedoat-Chalumeau⁴, Aurélie Hummel⁵, Véronique Le Guern⁴, Karim Sacre⁶, Olivier Meyer⁷, Eric Daugas⁸, Cecile Goujard⁹, Audrey Sultan², Thierry Lobbedez², Lionel Galicier¹⁰, Jacques Pourrat¹¹, Claire Le Hello², Michel Godin¹², Remy Morello², Marc Lambert¹³, Eric Hachulla¹³, Philippe Vanhille¹⁴, Guillaume Queffeulou¹⁵, Jacques Potier¹⁵, Jean Jacques Dion¹⁶, P Bataille¹⁷, Dominique Chauveau¹⁸, Guillaume Moulis¹⁹, Dominique Farge²⁰, Pierre Duhaut²¹, Bernadette Saint Marcoux²², Alban Deroux²³, Jennifer Manuzak²⁴, Camille Francès²⁵, Olivier Aumaître²⁶, Holy Bezanahary²⁷, Laurent Becquemont²⁸ and Boris Bienvenu²⁹, ¹Internal Medicine, CHU Caen, caen, France, ²CHU Caen, caen, France, ³Pharmacology, Hopital Bicêtre, Le Kremlin Bicêtre, France, ⁴Internal Medicine Department, Cochin Hospital, “René-Descartes Paris V” University, Paris, France, ⁵Necker, paris, France, ⁶Internal Medicine, Hospital Bichat, Paris, France, ⁷Rheumatology, Hopital Bichat, Paris, France, ⁸Internal Medicine, AP-HP Hôpital Bîchat, Paris, France, ⁹Bichat, Paris, France, ¹⁰Clinical Immunology, St Louis Hospital, Paris, France, ¹¹Nephrology, Rangeuil Hospital, Paris, France, ¹²CHU Rouen, Rouen, France, ¹³CHU Lille, Lille, France, ¹⁴Department of Nephrology and Internal Medicine, Hospital of Valenciennes, Valenciennes, France, Valenciennes, Valenciennes, France, ¹⁵Ch Cherbourg, Cherbourg, France, ¹⁶Ch Charleville Mezeiere, Charleville Mezeiere, France, ¹⁷Ch Boulogne sur Mer, Boulogne sur Mer, France, ¹⁸CH Toulouse, Toulouse, France, ¹⁹CHU Purpan, Toulouse, France, ²⁰Internal Medicine, Hopital St Louis, Paris, France, ²¹Department of Internal Medicine and RECIF, CHU Amiens, Amiens, France, ²²CH Aulnay sous Bois, Aulnay sous Bois, France, ²³Internal Medicine, CHU Grenoble, Grenoble, France, ²⁴Institut Cochin, Paris, France, ²⁵Dermatology Service, Tenon Hospital, Paris, France, ²⁶Department of Internal Medicine 2. Referal center for SLE/APS, CHU Pitié-Salpêtrière, Paris, France, ²⁷Internal Medicine, University Hospital of Limoges, Limoges, France, ²⁸KB, Paris, France, ²⁹Internal Medicine, Hospital Caen, Caen, France

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: cyclophosphamide, Genetic Biomarkers, Lupus nephritis, polymorphism and systemic lupus erythematosus (SLE)

Session Information

Date: Sunday, November 8, 2015

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Cyclophosphamide (CYC) is effective in inducing remission of lupus nephritis (LN). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). Methods: We conducted a retrospective study that included 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. We examined the association between these genotypes and achievement of renal response and occurrence of side effects. Results: In univariate analysis, patients expressing the GSTP1 null genotype showed a trend toward a lower probability of achieving renal response (73.3% versus 91.2%, p=0.059). Expression of the GSTM1 null genotype was associated with a higher occurrence of side effects (43.9% versus 21.4%, p<0.05). In multivariate analysis, the GSTP1 null genotype was an independent factor of treatment lower response (p<0.05). The only factor that influenced the occurrence of side effects was the polymorphism of GSTM1 (p<0.05). No association between polymorphisms of the cytochrome P450 gene and efficacy or side effects was observed. Conclusion: Despite small sample size, this study suggests that determination of GST genotypes may be valuable for predicting the renal response and occurrence of side effects in lupus nephritis patients treated with CYC.

Disclosure: A. Audemard-Verger, None; N. Martin Silva, None; C. Verstuyft, None; N. Costedoat-Chalumeau, None; A. Hummel, None; V. Le Guern, None; K. Sacre, None; O. Meyer, None; E. Daugas, None; C. Goujard, None; A. Sultan, None; T. Lobbedez, None; L. Galicier, None; J. Pourrat, None; C. Le Hello, None; M. Godin, None; R. Morello, None; M. Lambert, None; E. Hachulla, None; P. Vanhille, None; G. Queffeulou, None; J. Potier, None; J. J. Dion, None; P. Bataille, None; D. Chauveau, None; G. Moulis, None; D. Farge, None; P. Duhaut, None; B. Saint Marcoux, None; A. Deroux, None; J. Manuzak, None; C. Francès, None; O. Aumaître, None; H. Bezanahary, None; L. Becquemont, None; B. Bienvenu, None.

To cite this abstract in AMA style:

Audemard-Verger A, Martin Silva N, Verstuyft C, Costedoat-Chalumeau N, Hummel A, Le Guern V, Sacre K, Meyer O, Daugas E, Goujard C, Sultan A, Lobbedez T, Galicier L, Pourrat J, Le Hello C, Godin M, Morello R, Lambert M, Hachulla E, Vanhille P, Queffeulou G, Potier J, Dion JJ, Bataille P, Chauveau D, Moulis G, Farge D, Duhaut P, Saint Marcoux B, Deroux A, Manuzak J, Francès C, Aumaître O, Bezanahary H, Becquemont L, Bienvenu B. Glutathione S Transferases (GST) Polymorphisms Are Independents Predictors of Efficacy and Toxicity in Lupus Nephritis Treated with Cyclophosphamide [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/glutathione-s-transferases-gst-polymorphisms-are-independents-predictors-of-efficacy-and-toxicity-in-lupus-nephritis-treated-with-cyclophosphamide/. Accessed .

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