Impact of switching from mycophenolate mofetil to enteric-coated mycophenolate sodium on gastrointestinal side effects in patients with autoimmune disease: a Phase III, open-label, single-arm, multicenter study

Abstract

Bernhard Manger,1 Falk Hiepe,2 Matthias Schneider,3 Margitta Worm,4 Peter Wimmer,5 Eva-Maria Paulus,5 Andreas Schwarting6 1University Hospital Erlangen, Med Clinic III Polyclinic, Erlangen, 2Rheumatology, University Hospital Charité, Campus Mitte, Berlin, 3Policlinic of Rheumatology, Heinrich-Heine-Universität, Düsseldorf, 4Department of Dermatology, Venereology and Allergology, University Hospital Charité, Campus Mitte, Berlin, 5Novartis Pharma GmbH, Nürnberg, 6Department of Internal Medicine, Johannes Gutenberg University, Mainz, Germany Background: The purpose of this study was to assess changes in gastrointestinal symptom severity in patients with autoimmune disease who were switched from mycophenolate mofetil to enteric-coated mycophenolate sodium (EC-MPS). Methods: In this national, explorative, single-arm study, 111 patients were enrolled and switched to equimolar EC-MPS at baseline. The primary endpoint was change in the Gastrointestinal Symptom Rating Scale (GSRS) total score after 6–8 weeks of treatment (Visit 2). The optional follow-up visit was 6–12 weeks after completion of the study (Visit 2). Secondary endpoints were changes in GSRS subscale score; changes in gastrointestinal-related quality of life measured by the Gastrointestinal Quality of Life Index (GIQLI); and general health-related quality of life (HRQoL) measured by Psychological General Well-Being Index and assessment of overall treatment effect (OTE). Change was evaluated by paired t-tests. Results: At Visit 2, the mean ± standard deviation GSRS total score improved from 2.28±1.13 to 2.02±0.93 points. The change (-0.28±0.92 points, P=0.002) was statistically significant. The change at the follow-up visit (-0.36±0.94 points, P=0.001) was statistically significant and more than the minimal clinical important difference. GSRS subscores showed statistically significant and clinically relevant improvement for abdominal pain (-0.51±1.2 points, P<0.001) and indigestion (-0.42±1.33 points, P=0.002). Overall GIQLI score showed significant improvement from baseline to Visit 2 (-5.8±18.6 points, P=0.002). Per OTE, improvement was reported in 44.1% and 34.2% patients as rated by physicians and patients, respectively. The majority of patients (55%) reported OTE-HRQoL as unchanged. Diarrhea and nausea were the commonly reported adverse events. Conclusion: Patients switched to EC-MPS experienced less gastrointestinal symptom burden and showed improvement in HRQoL. Keywords: mycophenolate mofetil, enteric-coated mycophenolate sodium, autoimmune disease, patient-reported outcome, health-related quality of life