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

Clinical and Experimental Gastroenterology, Jul 2015

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 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

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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

Clinical and Experimental Gastroenterology 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 Bernhard Manger 2 Margitta Worm 5 Peter Wimmer 4 Eva-Maria Paulus 4 0 Policlinic of rheumatology, heinrichheine-Universität , Düsseldorf 1 rheumatology, University hospital Charité , Campus Mitte, Berlin 2 University hospital Erlangen, Med Clinic iii Polyclinic , Erlangen 3 Department of internal Medicine, Johannes Gutenberg University , Mainz , Germany 4 n ovartis Pharma Gmbh , n ürnberg 5 Department of Dermatology, Venereology and allergology, University hospital Charité , Campus Mitte, Berlin 8 1 0 2 - l u J - 2 1 n o 7 0 2 . 6 4 . 9 5 . 7 3 y b / m o c . s s e r p e v o d . ww l.y /w no / : tsp sue th la ldedao rpeoF PowerdbyTCPDF(ww.tcpdf.org) Falk hiepe 2 Matthias schneider 3 andreas schwarting 6 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. patient-reported outcome, health-related quality of life mycophenolate mofetil; enteric-coated mycophenolate sodium; autoimmune disease - n w o d y g o l o r e t n e o tr s a G l a t n e m i r e p x E d n a l a c i n il C open access to scientific and medical research Introduction The pharmacological activity of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) is derived entirely from mycophenolic acid (MPA).1,2 MPA is a potent, selective, and reversible inhibitor of inosine monophosphate dehydrogenase and inhibits the de novo pathway of guanosine nucleotide synthesis. MPA predominantly inhibits lymphocyte proliferation, because T-lymphocytes and B-lymphocytes are critically dependent on de novo synthesis of purines.3,4 MMF is rapidly and completely cleaved by gastrointestinal (GI) and liver esterases to yield MPA and morpholino ethanol.3,5 Although MMF is a highly potent agent that has contrib8 uted to improvement of immunosuppressive regimens, the 201 efficacy has been limited by unwanted side effects, such as l--Ju GI complications, including vomiting, diarrhea, esophagitis, 2n1 gastritis, and bleeding.6 EC-MPS has been designed to reduce 7o MPA-related upper GI adverse events (AEs) by allowing .620 for delivery of the active substance into the small intestine ..594 without compromising safety and tolerability.7 y37 The efficacy and safety of EC-MPS has been shown for /b rejection prophylaxis in de novo8 and maintenance9 renal .com transplant patients. The pivotal trials were designed to rsse demonstrate therapeutic equivalence between EC-MPS and vpeo MMF. EC-MPS 720 mg has been shown to be bioequivalent10 .dww l.y to MMF 1,000 mg in terms of area under the curve, besides /w no being shown as therapeutically equivalent.8 The maintenance / : tsp sue study showed that conversion from MMF to EC-MPS did not ltdedaoohm lrspeoonaF scaofmelpyroamndiseeffseacfteivtye,lyi.n9dicating patients could be converted fr r A recent study in MMF-treated renal transplant patients with mild, moderate, or severe GI complaints showed that conversion f (...truncated)


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Bernhard Manger, Falk Hiepe, Matthias Schneider, Margitta Worm, Peter Wimmer, Eva-Maria Paulus, Andreas Schwarting. 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, Clinical and Experimental Gastroenterology, 2015, pp. 205-213, DOI: 10.2147/CEG.S81922