Paul Legendre1, Benoit Blanchet2,3,4, Raphael Porcher5, Alice Bérezné1, Marie Allard2, Jonathan London1, Benjamin Terrier1,4, Pascal Cohen1, Claire Le Jeunne1, Luc Mouthon1,6. 1. Service de Médecine Interne, Hôpital Cochin, Centre de Référence pour les Maladies Systémiques Autoimmunes Rares d'Ile de France, DHU Authors, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. 2. UF de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, AP-HP, Paris, France. 3. UMR8638 CNRS, Pharmacy UFR, University of Paris Descartes, PRES Sorbonne Paris Cité, Paris, France. 4. RAPIDEM (Research on Autoimmune Disease for Personalized Medicine), Paris, France. 5. Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Descartes, Paris, France. 6. Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Paris, France.
Abstract
Objective: To explore pharmacokinetic/pharmacodynamic relationship between mycophenolic acid area under the curve and clinical response at 1 year on skin involvement or interstitial lung disease in patients with systemic sclerosis. Method: Retrospective, monocentric study based on French Scleroderma Database in patients receiving mycophenolate mofetil who experienced a limited sampling strategy to estimate individual mycophenolic acid area under the curve plus two pulmonary function tests and skin evaluation after 1 month and 1 year. Efficacy criterions were variations of modified Rodnan skin score, forced vital capacity, and diffusing lung capacity for carbon monoxide at 1 year. Results: We included 52 patients; mean age was 49 years (range 17-79), and 36 (69%) were females. Fifty patients (96%) had skin sclerosis, 39 (75%) had diffuse skin involvement with a median modified Rodnan skin score of 14 (0-38). Thirty-eight (76%) had interstitial lung disease, with median forced vital capacity and diffusing lung capacity for carbon monoxide of 81% (37-127) and 56% (28-103) from predicted values, respectively. Twenty-five (51%) patients had pulmonary fibrosis. Mycophenolate mofetil was given for 10 months (0-173) at a median dose of 2000 mg/day (500-3000). In the entire population, no relationship was found between area under the curve and modified Rodnan skin score (p = 0.085), forced vital capacity (p = 0.80), or diffusing lung capacity for carbon monoxide (p = 0.72) variations at 1 year. Conclusion: In this retrospective study, we failed to document any relationship between mycophenolic acid area under the curve and skin involvement or interstitial lung disease evolution. Routine monitoring of mycophenolic acid in systemic sclerosis patients treated with mycophenolate mofetil cannot be recommended based on our results.
Objective: To explore pharmacokinetic/pharmacodynamic relationship between mycophenolic acid area under the curve and clinical response at 1 year on skin involvement or interstitial lung disease in patients with systemic sclerosis. Method: Retrospective, monocentric study based on French Scleroderma Database in patients receiving mycophenolate mofetil who experienced a limited sampling strategy to estimate individual mycophenolic acid area under the curve plus two pulmonary function tests and skin evaluation after 1 month and 1 year. Efficacy criterions were variations of modified Rodnan skin score, forced vital capacity, and diffusing lung capacity for carbon monoxide at 1 year. Results: We included 52 patients; mean age was 49 years (range 17-79), and 36 (69%) were females. Fifty patients (96%) had skin sclerosis, 39 (75%) had diffuse skin involvement with a median modified Rodnan skin score of 14 (0-38). Thirty-eight (76%) had interstitial lung disease, with median forced vital capacity and diffusing lung capacity for carbon monoxide of 81% (37-127) and 56% (28-103) from predicted values, respectively. Twenty-five (51%) patients had pulmonary fibrosis. Mycophenolate mofetil was given for 10 months (0-173) at a median dose of 2000 mg/day (500-3000). In the entire population, no relationship was found between area under the curve and modified Rodnan skin score (p = 0.085), forced vital capacity (p = 0.80), or diffusing lung capacity for carbon monoxide (p = 0.72) variations at 1 year. Conclusion: In this retrospective study, we failed to document any relationship between mycophenolic acid area under the curve and skin involvement or interstitial lung disease evolution. Routine monitoring of mycophenolic acid in systemic sclerosis patients treated with mycophenolate mofetil cannot be recommended based on our results.
Authors: Susan E Tett; Franck Saint-Marcoux; Christine E Staatz; Merce Brunet; Alexander A Vinks; Masatomo Miura; Pierre Marquet; Dirk R Kuypers; Teun van Gelder; Dario Cattaneo Journal: Transplant Rev (Orlando) Date: 2010-12-28 Impact factor: 3.943
Authors: Michael Walsh; Matthew James; David Jayne; Marcello Tonelli; Braden J Manns; Brenda R Hemmelgarn Journal: Clin J Am Soc Nephrol Date: 2007-08-08 Impact factor: 8.237
Authors: Gunnar Brandhorst; Pierre Marquet; Leslie M Shaw; Gerhard Liebisch; Gerd Schmitz; Mary Jane Coffing; Ingrid Domke; Frank Streit; Hilmar Luthe; Michael Oellerich Journal: Ther Drug Monit Date: 2008-08 Impact factor: 3.681
Authors: M Vanthuyne; D Blockmans; R Westhovens; F Roufosse; E Cogan; E Coche; A Nzeusseu Toukap; G Depresseux; F A Houssiau Journal: Clin Exp Rheumatol Date: 2007 Mar-Apr Impact factor: 4.473
Authors: Donald P Tashkin; Michael D Roth; Philip J Clements; Daniel E Furst; Dinesh Khanna; Eric C Kleerup; Jonathan Goldin; Edgar Arriola; Elizabeth R Volkmann; Suzanne Kafaja; Richard Silver; Virginia Steen; Charlie Strange; Robert Wise; Fredrick Wigley; Maureen Mayes; David J Riley; Sabiha Hussain; Shervin Assassi; Vivien M Hsu; Bela Patel; Kristine Phillips; Fernando Martinez; Jeffrey Golden; M Kari Connolly; John Varga; Jane Dematte; Monique E Hinchcliff; Aryeh Fischer; Jeffrey Swigris; Richard Meehan; Arthur Theodore; Robert Simms; Suncica Volkov; Dean E Schraufnagel; Mary Beth Scholand; Tracy Frech; Jerry A Molitor; Kristin Highland; Charles A Read; Marvin J Fritzler; Grace Hyun J Kim; Chi-Hong Tseng; Robert M Elashoff Journal: Lancet Respir Med Date: 2016-07-25 Impact factor: 30.700