IMPROVE: Mycophenolate Mofetil Versus Azathioprine for Maintenance Therapy in ANCA Associated Systemic Vasculitis

Summary

The aim of IMPROVE is to define the optimal maintenance therapy for ANCA-associated vasculitides (AASV) by comparing the AZA (standard regimen) with MMF in terms of efficacy, i.e. in preventing relapses. HYPOTHESIS : MMF might be more effective than azathioprine as maintenance drug in AASV patients, reducing by 50% relapse rate, with a same frequency of adverse effects

Timeline

Start

2003-05

Primary completion

—

Completion

2009-08

Outcome

Missed primary endpoint

paper unadjusted hazard ratio (HR) for mycophenolate mofetil of 1.69 (95% confidence interval [CI], 1.06-2.70; P = .03). PMID 21060104 ↗

paper mycophenolate mofetil was less effective than azathioprine for maintaining disease remission. PMID 21060104 ↗

Publications

• Morgan MD, Szeto M, Walsh M, Jayne D, Westman K, Rasmussen N, Hiemstra TF, Flossmann O, Berden A, Hoglund P, Harper L; European Vasculitis Society. Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse. Arthritis Res Ther. 2017 Jun 7;19(1):129. doi: 10.1186/s13075-017-1321-1.
• Hiemstra TF, Walsh M, Mahr A, Savage CO, de Groot K, Harper L, Hauser T, Neumann I, Tesar V, Wissing KM, Pagnoux C, Schmitt W, Jayne DR; European Vasculitis Study Group (EUVAS). Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA. 2010 Dec 1;304(21):2381-8. doi: 10.1001/jama.2010.1658. Epub 2010 Nov 8.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Azathioprine	Small molecule	2 mg/kg	—
Subject	Mycophenolate Mofetil	Small molecule	2000 mg	—
Background	Cyclophosphamide	Other / unclassified	—	—
Background	Methylprednisolone	Other / unclassified	—	—
Background	Prednisone	Other / unclassified	—	—

Indications