Rheumatology 2000; 39: 156-164
© 2000 British Society for Rheumatology
Microemulsion formulation of cyclosporin (Sandimmun Neoral®) vs Sandimmun®: comparative safety, tolerability and efficacy in severe active rheumatoid arthritis
Arizona Arthritis Center, University of Arizona, Tucson, Arizona, USA,
1 Department of Rheumatology, West Middlesex University Hospital, Middlesex, UK,
2 Metroplex Clinical Research Center, Dallas, Texas, USA,
3 School of Medicine, Rheumatology and Rehabilitation Research Unit, University of Leeds, Leeds, UK,
4 Rhumatologie, Hôpital Roger Salengro, Lille, France,
5 Hospital for Rheumatic Diseases, Ostersund,
6 Medicinmottagningen, Bollnäs Iasarett Medicinklinikum, Bollnäs, Sweden,
7 Groupe Hospitalier Cochin, Paris, France,
8 Rheumatology Department, Selly Oak Hospital, Birmingham, UK,
9 Universitätskliniken links der Isar, Med Poliklinik, Munich, Germany,
10 Hospital S João, Unidade de Reumatologia, Porto, Portugal,
11 Rheumatologie, Universitätsklinik, Medizinische Klinik III, Erlangen, Germany,
12 Universtitätsklinik Innsbruck, Rheumaambulanz, Innsbruck, Austria,
13 The Rheumatism Hospital, Lillehammer, Norway,
14 Division of Rheumatology and Clinical Immunology, Department of Medicine, University Hospital, Freiburg, Germany
15 Medizinische Universitätsklinik, Graz, Austria,
16 Center for Clinical Research, Austin Diagnostic Clinic, Austin, Texas,
17 Denver Arthritis Clinic, Denver, Colorado,
18 Northwestern University, Office of Clinical Research and Training, Chicago, Illinois,
19 Little Rock Diagnostic Center, Little Rock, Arkansas, USA and
20 Novartis Pharma AG, Basel, Switzerland
Objective. To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral®) and the original CyA formulation (Sandimmun®), in patients with severe active rheumatoid arthritis (RA), over a 12-month period.
Methods. In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients’ assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals.
Results. Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients’ assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups.
Conclusion. These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.
KEY WORDS: Rheumatoid arthritis, Cyclosporin, Microemulsion formulation
22 Correspondence to: D. Yocum, Director—Arizona Arthritis Center, University of Arizona, Health Science Center, Room 6409, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA.
Additional members of the Neoral/RA OLR 302 Study Group include: D. Becker-Capeller, P. Bertin, C. M. Black, M. I. D. Cawley, B. Combe, M. Dougados, E. Fjeld, N. Gerber, I. M. Gilboe, E. Gromnica-Ihle, G. Hein, K. Helmke, D. W. James, J. P. Kaltwasser, T. K. Kvien, P. E. McGill, G. Myklebust, A. Nicholls, H.-H. Peter, D. M. Reid, P. J. Smith and H. Zeidler.