Mycophenolate sodium treatment in patients with primary Sjögren syndrome: a pilot trial

Peter Willeke, Bernhard Schlüter, Heidemarie Becker, Heiko Schotte, Wolfram Domschke, Markus Gaubitz, Peter Willeke, Bernhard Schlüter, Heidemarie Becker, Heiko Schotte, Wolfram Domschke, Markus Gaubitz

Abstract

The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium (MPS) in patients with primary Sjögren syndrome (pSS) refractory to other immunosuppressive agents. Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center, open-label pilot trial. At baseline, after 3 months, and after 6 months, we examined the clinical status, including glandular function tests, as well as different laboratory parameters associated with pSS. In addition, subjective parameters were determined on the basis of different questionnaires. Treatment with MPS was well tolerated in 8 of 11 patients. Due to vertigo or gastrointestinal discomfort, two patients did not complete the trial. One patient developed pneumonia 2 weeks after treatment and was withdrawn. In the remaining patients, MPS treatment resulted in subjective improvement of ocular dryness on a visual analogue scale and a reduced demand for artificial tear supplementations. However, no significant alterations of objective parameters for dryness of eyes and mouth were observed, although a substantial improvement of glandular functions occurred in two patients with short disease duration. In addition, treatment with MPS resulted in significant reduction of hypergammaglobulinemia and rheumatoid factors as well as an increase of complement levels and white blood cells. MPS promises to be an additional therapeutic option for patients with pSS, at least in those with shorter disease duration. Further investigations about the efficacy and safety of MPS in pSS have to be performed in larger numbers of patients.

Figures

Figure 1
Figure 1
Short Form 36 (SF-36) at baseline and after 24 weeks of treatment with mycophenolate sodium in patients with primary Sjögren syndrome (n = 8). The SF-36 domains are physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), mental health (MH), and the physical and mental component summary scores (PCS and MCS). The GH and RE domains increased significantly (p < 0.05) after 24 weeks (*). The increase of the MCS did not reach significance (**p = 0.06).

References

    1. Tomiak C, Dorner T. Sjogren's syndrome: current aspects from a rheumatological point of view. Z Rheumatol. 2006;65:505–519. doi: 10.1007/s00393-006-0101-0.
    1. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000;47:85–118. doi: 10.1016/S0162-3109(00)00188-0.
    1. Hansen A, Lipsky PE, Dörner T. B cells in Sjögren's syndrome: indications for disturbed selection and differentiation in ectopic lymphoid tissue. Arthritis Res Ther. 2007;6:218. doi: 10.1186/ar2210.
    1. Pers JO, Devauchelle V, Daridon C, Bendaoud B, Berre RL, Bordron A, Hutin P, Renaudineau Y, Dueymes M, Loisel S, et al. BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of Rituximab-treated patients with Sjogren's syndrome. Arthritis Rheum. 2007;56:1464–1477. doi: 10.1002/art.22603.
    1. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. European Mycophenolate Mofetil Cooperative Study Group. Lancet. 1995;345:1321–1325.
    1. Pietruck F, Abbud-Filho M, Vathsala A, Massari PU, Po-Huang L, Nashan B. Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable maintenance renal transplant patients: pooled results from three international, multicenter studies. Transplant Proc. 2007;39:103–108. doi: 10.1016/j.transproceed.2006.10.216.
    1. Gaubitz M, Schorat A, Schotte H, Kern P, Domschke W. Mycophenolate mofetil for the treatment of systemic lupus erythematosus: an open pilot trial. Lupus. 1999;8:731–736. doi: 10.1191/096120399678840927.
    1. Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, Petri M, Gilkeson GS, Wallace DJ, Weisman MH, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005;353:2219–2228. doi: 10.1056/NEJMoa043731.
    1. Schneider-Gold C, Hartung HP, Gold R. Mycophenolate mofetil and tacrolimus: new therapeutic options in neuroimmunological diseases. Muscle Nerve. 2006;34:284–291. doi: 10.1002/mus.20543.
    1. Appel GB, Radhakrishnan J, Ginzler EM. Use of mycophenolate mofetil in autoimmune and renal diseases. Transplantation. 2005;80:S265–S271. doi: 10.1097/01.tp.0000186389.19911.9c.
    1. Ahmadi-Simab K, Lamprecht P, Nolle B, Ai M, Gross WL. Successful treatment of refractory anterior scleritis in primary Sjogren's syndrome with rituximab. Ann Rheum Dis. 2005;64:1087–1088. doi: 10.1136/ard.2004.027128.
    1. Willeke P, Domschke W, Gaubitz M. Mycophenolate Mofetil for the treatment of primary Sjögren's Syndrome: a case report. Ann Rheum Dis. 2003;62(Suppl 1):352.
    1. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, et al. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554–558. doi: 10.1136/ard.61.6.554.
    1. Kallarackal GU, Ansari EA, Amos N, Martin JC, Lane C, Camilleri JP. A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT) with Tear Break up Time (TBUT) and Schirmer's tests (ST) in the diagnosis of dry eyes. Eye. 2002;16:594–600. doi: 10.1038/sj.eye.6700177.
    1. Navazesh M, Christensen CM. A comparison of whole mouth resting and stimulated salivary measurement procedures. J Dent Res. 1982;61:1158–1162.
    1. Ware JE, Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30:473–483. doi: 10.1097/00005650-199206000-00002.
    1. Strombeck B, Ekdahl C, Manthorpe R, Wikstrom I, Jacobsson L. Health-related quality of life in primary Sjogren's syndrome, rheumatoid arthritis and fibromyalgia compared to normal population data using SF-36. Scand J Rheumatol. 2000;29:20–28. doi: 10.1080/030097400750001761.
    1. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980;23:137–145. doi: 10.1002/art.1780230202.
    1. Mavragani CP, Moutsopoulos NM, Moutsopoulos HM. The management of Sjogren's syndrome. Nat Clin Pract Rheumatol. 2006;2:252–261. doi: 10.1038/ncprheum0165.
    1. Pijpe J, van Imhoff GW, Vissink A, van der Wal JE, Kluin PM, Spijkervet FK, Kallenberg CG, Bootsma H. Changes in salivary gland immunohistology and function after rituximab monotherapy in a patient with Sjogren's syndrome and associated MALT lymphoma. Ann Rheum Dis. 2005;64:958–960. doi: 10.1136/ard.2004.030684.
    1. Pijpe J, van Imhoff GW, Spijkervet FK, Roodenburg JL, Wolbink GJ, Mansour K, Vissink A, Kallenberg CG, Bootsma H. Rituximab treatment in patients with primary Sjogren's syndrome: an open-label phase II study. Arthritis Rheum. 2005;52:2740–2750. doi: 10.1002/art.21260.
    1. Iaccarino L, Rampudda M, Canova M, Della Libera S, Doria A. Mycophenolate mofetil: what is its place in the treatment of autoimmune rheumatic diseases? Autoimmun Rev 190. 2007;6:190–195. doi: 10.1016/j.autrev.2006.11.001.
    1. Asmussen KH, Bowman SJ. Outcome measures in Sjogren's syndrome. Rheumatology (Oxford) 2001;40:1085–1088. doi: 10.1093/rheumatology/40.10.1085.
    1. Mariette X. Lymphomas complicating Sjogren's syndrome and hepatitis C virus infection may share a common pathogenesis: chronic stimulation of rheumatoid factor B cells. Ann Rheum Dis. 2001;60:1007–1010. doi: 10.1136/ard.60.11.1007.
    1. Theander E, Henriksson G, Ljungberg O, Mandl T, Manthorpe R, Jacobsson LT. Lymphoma and other malignancies in primary Sjogren's syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis. 2006;65:796–803. doi: 10.1136/ard.2005.041186.
    1. Devauchelle-Pensec V, Pennec Y, Morvan J, Pers JO, Daridon C, Jousse-Joulin S, Roudaut A, Jamin C, Renaudineau Y, Roue IQ, et al. Improvement of Sjogren's syndrome after two infusions of rituximab (anti-CD20) Arthritis Rheum. 2007;57:310–317. doi: 10.1002/art.22536.
    1. Bowman SJ, Pillemer S, Jonsson R, Asmussen K, Vitali C, Manthorpe R, Sutcliffe N. Revisiting Sjogren's syndrome in the new millennium: perspectives on assessment and outcome measures. Report of a workshop held on 23 March 2000 at Oxford, UK. Rheumatology (Oxford) 2001;40:1180–1188. doi: 10.1093/rheumatology/40.10.1180.
    1. Steinfeld SD, Tant L, Burmester GR, Teoh NK, Wegener WA, Goldenberg DM, Pradier O. Epratuzumab (humanised anti-CD22 antibody) in primary Sjogren's syndrome: an open-label phase I/II study. Arthritis Res Ther. 2006;8:R129. doi: 10.1186/ar2018.
    1. Schattner A, Friedman J, Klepfish A, Berrebi A. Immune cytopenias as the presenting finding in primary Sjogren's syndrome. QJM. 2000;93:825–829. doi: 10.1093/qjmed/93.12.825.
    1. Granger DK. Enteric-coated mycophenolate sodium: results of two pivotal global multicenter trials. Transplant Proc. 2001;33:3241–3244. doi: 10.1016/S0041-1345(01)02378-8.

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