Clinical Rheumatology

, Volume 26, Issue 8, pp 1320–1327

Efficacy prediction of cevimeline in patients with Sjögren’s syndrome

  • Hiroyuki Yamada
  • Yoichi Nakagawa
  • Ei Wakamatsu
  • Takayuki Sumida
  • Shigeo Yamachika
  • Yoshiaki Nomura
  • Kenji Mishima
  • Ichiro Saito
Original Article


The objective of this study was to examine the clinical and immunological factors influencing the efficacy of cevimeline hydrochloride hydrate (cevimeline) for the treatment of xerostomia in patients with Sjögren’s syndrome (SS). Thirty primary SS patients who were medicated with cevimeline were enrolled in this study. Whole stimulated sialometry (WSS) was compared between pre- and posttreatment points (4 weeks after oral cevimeline administration) and the increment rate of WSS was calculated. Multiple regression was employed to examine the relative contributions of the clinical and immunological factors, including age, pretreatment WSS, duration of disease, sialography, minor salivary gland biopsy, anti-Ro/SS-A antibodies, anti-La/SS-B antibodies, and antibodies to muscarinic type 3 receptors to the posttreatment WSS. Patients with normal sialography findings, negative minor salivary gland biopsy, and absence of anti-La/SS-B antibodies had significantly higher increment rates of WSS compared with those with positive findings (p = 0.042, 0.002, and 0.018, respectively). Results of the multiple regression analysis showed that sialography (coefficient = −0.867, p = 0.004) and minor salivary gland biopsy (coefficient = −0.869, p = 0.003) had significant associations with the posttreatment WSS. Our preliminary results demonstrated the relationship between the effect of cevimeline on saliva secretion and the degree of salivary gland destruction evaluated by sialography and histopathological findings in the labial minor salivary glands. These diagnostic approaches could provide useful prognostic information on the efficacy of cevimeline in SS patients.


Cevimeline Labial minor salivary gland Muscarinic type 3 receptor Sialography Sjögren’s syndrome 


  1. 1.
    Fox RI, Saito I (1994) Criteria for diagnosis of Sjögren’s syndrome. Rheum Dis Clin North Am 20:391–407PubMedGoogle Scholar
  2. 2.
    Fox PC (2004) Salivary enhancement therapies. Caries Res 38:241–246PubMedCrossRefGoogle Scholar
  3. 3.
    Iwabuchi Y, Katagiri M, Masuhara T (1994) Salivary secretion and histopathological effects after single administration of the muscarinic agonist SNI-2011 in MRL/lpr mice. Arch Int Pharmacodyn Ther 328:315–325PubMedGoogle Scholar
  4. 4.
    Fife RS, Chase WF, Dore RK, Wiesenhutter CW, Lockhart PB, Tindall E, Suen JY (2002) Cevimeline for the treatment of xerostomia in patients with Sjögren syndrome: a randomized trial. Arch Intern Med 162:1293–1300PubMedCrossRefGoogle Scholar
  5. 5.
    Petrone D, Condemi JJ, Fife R, Gluck O, Cohen S, Dalgin P (2002) A double-blind, randomized, placebo-controlled study of cevimeline in Sjögren’s syndrome patients with xerostomia and keratoconjunctivitis sicca. Arthritis Rheum 46:748–754PubMedCrossRefGoogle Scholar
  6. 6.
    Gao J, Cha S, Jonsson R, Opalko J, Peck AB (2004) Detection of anti-type 3 muscarinic acetylcholine receptor autoantibodies in the sera of Sjögren’s syndrome patients by use of a transfected cell line assay. Arthritis Rheum 50:2615–2621PubMedCrossRefGoogle Scholar
  7. 7.
    Dawson LJ, Stanbury J, Venn N, Hasdimir B, Rogers SN, Smith PM (2006) Antimuscarinic antibodies in primary Sjögren’s syndrome reversibly inhibit the mechanism of fluid secretion by human submandibular salivary acinar cells. Arthritis Rheum 54:1165–1173PubMedCrossRefGoogle Scholar
  8. 8.
    Fujibayashi T, Sugai S, Miyasaka N, Hayashi Y, Tsubota K (2004) Revised Japanese criteria for Sjögren’s syndrome (1999): availability and validity. Mod Rheumatol 14:425–434CrossRefGoogle Scholar
  9. 9.
    Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61:554–558PubMedCrossRefGoogle Scholar
  10. 10.
    Rubin P, Holt JF (1957) Secretory sialography in diseases of the major salivary glands. Am J Roentgenol Radium Ther Nucl Med 77:575–598PubMedGoogle Scholar
  11. 11.
    Greenspan JS, Daniels TE, Talal N, Sylvester RA (1974) The histopathology of Sjögren’s syndrome in labial salivary gland biopsies. Oral Surg Oral Med Oral Pathol 37:217–229PubMedCrossRefGoogle Scholar
  12. 12.
    Naito Y, Matsumoto I, Wakamatsu E, Goto D, Sugiyama T, Matsumura R, Ito S, Tsutsumi A, Sumida T (2005) Muscarinic acetylcholine receptor autoantibodies in patients with Sjögren’s syndrome. Ann Rheum Dis 64:510–511PubMedCrossRefGoogle Scholar
  13. 13.
    Rosas J, Ramos-Casals M, Ena J, Garcia-Carrasco M, Verdu J, Cervera R, Font J, Caballero O, Ingelmo M, Pascual E (2002) Usefulness of basal and pilocarpine-stimulated salivary flow in primary Sjögren’s syndrome. Correlation with clinical, immunological and histological features. Rheumatology (Oxford) 41:670–675CrossRefGoogle Scholar
  14. 14.
    Vivino FB, Al-Hashimi I, Khan Z, LeVeque FG, Salisbury PL III, Tran-Johnson TK, Muscoplat CC, Trivedi M, Goldlust B, Gallagher SC (1999) Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med 159:174–181PubMedCrossRefGoogle Scholar
  15. 15.
    Papas AS, Sherrer YS, Charney M, Golden HE, Medsger TA Jr, Walsh BT, Trivedi M, Goldlust B, Gallagher SC (2004) Successful treatment of dry mouth and dry eye symptoms in Sjögren’s syndrome patients with oral pilocarpine: a randomized, placebo-controlled, dose-adjustment study. J Clin Rheumatol 10:169–177PubMedCrossRefGoogle Scholar
  16. 16.
    Matsumura R, Umemiya K, Kagami M, Tomioka H, Tanabe E, Sugiyama T, Sueishi M, Nakajima A, Azuma M, Okumura K, Sumida T (1998) Glandular and extraglandular expression of the Fas–Fas ligand and apoptosis in patients with Sjögren’s syndrome. Clin Exp Rheumatol 16:561–568PubMedGoogle Scholar
  17. 17.
    Edgar WM (1992) Saliva: its secretion, composition and functions. Br Dent J 172:305–312PubMedGoogle Scholar
  18. 18.
    Saito T, Fukuda H, Arisue M, Matsuda A, Shindoh M, Amemiya A, Ohmori K (1991) Relationship between sialographic findings of parotid glands and histopathologic finding of labial glands in Sjögren’s syndrome. Relation to clinical and immunologic findings. Oral Surg Oral Med Oral Pathol 72:675–680PubMedCrossRefGoogle Scholar
  19. 19.
    Robinson CP, Brayer J, Yamachika S, Esch TR, Peck AB, Stewart CA, Peen E, Jonsson R, Humphreys-Beher MG (1998) Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren’s syndrome. Proc Natl Acad Sci USA 95:7538–7543PubMedCrossRefGoogle Scholar
  20. 20.
    Yamamoto H, Sims NE, Macauley SP, Nguyen KH, Nakagawa Y, Humphreys-Beher MG (1996) Alterations in the secretory response of non-obese diabetic (NOD) mice to muscarinic receptor stimulation. Clin Immunol Immunopathol 78:245–255PubMedCrossRefGoogle Scholar
  21. 21.
    Nguyen KH, Brayer J, Cha S, Diggs S, Yasunari U, Hilal G, Peck AB, Humphreys-Beher MG (2000) Evidence for antimuscarinic acetylcholine receptor antibody-mediated secretory dysfunction in nod mice. Arthritis Rheum 43:2297–2306PubMedCrossRefGoogle Scholar
  22. 22.
    Washio T, Kohsaka K, Arisawa H, Masunaga H (2003) Pharmacokinetics and metabolism of the novel muscarinic receptor agonist SNI-2011 in rats and dogs. Arzneimittelforschung 53:26–33PubMedGoogle Scholar

Copyright information

© Clinical Rheumatology 2007

Authors and Affiliations

  • Hiroyuki Yamada
    • 1
  • Yoichi Nakagawa
    • 2
  • Ei Wakamatsu
    • 4
  • Takayuki Sumida
    • 4
  • Shigeo Yamachika
    • 2
  • Yoshiaki Nomura
    • 3
  • Kenji Mishima
    • 1
  • Ichiro Saito
    • 1
  1. 1.Department of PathologyTsurumi University School of Dental MedicineYokohamaJapan
  2. 2.Second Department of Oral and Maxillofacial SurgeryTsurumi University School of Dental MedicineYokohamaJapan
  3. 3.Department of Preventive Dentistry and Public HealthTsurumi University School of Dental MedicineYokohamaJapan
  4. 4.Department of Internal MedicineUniversity of TsukubaIbarakiJapan

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