Skip to main content
Log in

Cyclosporin in Rheumatoid Arthritis

Monitoring for Adverse Effects and Clinically Significant Drug Interactions

  • Disease Management
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

While cyclosporin has an established role in the treatment of rheumatoid arthritis there is concern about adverse effects, mainly related to renal function. With new interest being generated in cyclosporin combination therapy, and the availability of a new form of cyclosporin (cyclosporin microemulsion), focus on adverse effects and drug interactions of this compound remains important.

Over the years, rheumatologists have been aware of these adverse effects and consensus meetings have resulted in guidelines for the use of cyclosporin. If these guidelines are followed, structural renal damage can be minimal. Cyclosporin should be started at a low dose and titrated against the highest acceptable increase in serum creatinine, that is, a 30% increase over the pretreatment value. At present, there is no evidence that cyclosporin in combination with other antirheumatics leads to increased toxicity With regard to long term unwanted effects, neither the pattern nor the risk of malignancies associated with the use of cyclosporin seems to differ from other antirheumatics.

The place of cyclosporin in the treatment of rheumatoid arthritis seems to be established. The most promising results will come from early rheumatoid arthritis combination studies involving cyclosporin with other antirheumatics, especially methotrexate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gupta SK, Benet LZ. High-fat meals increase the clearance of cyclosporin. Pharm Res 1990; 7: 46–8

    Article  PubMed  CAS  Google Scholar 

  2. Lucey ML, Kolars JC, Merion KM, et al. Cyclosporin toxicity at therapeutic blood levels and cytochrome P-450 IIIa. Lancet 1990; 335: 11–5

    Article  PubMed  CAS  Google Scholar 

  3. Kahan BD. Cyclosporin. New Eng J Med 1989; 16: 415–22

    Google Scholar 

  4. Maurer G, Loosli HR, Schreier E, et al. Disposition of cyclosporin in several animal species and man. Structural elucidation of its metabolites. Drug Metab Dispos 1984; 12: 120–6

    PubMed  CAS  Google Scholar 

  5. Borne van den BEEM, Landewe RBM, Goei Thè HS, et al. Relative bioavailability of a new oral form of cyclosporin A in patients with rheumatoid arthritis. Br J Clin Pharmacol 1995; 39: 172–5

    Article  PubMed  Google Scholar 

  6. Furst DE. Cyclosporin, leflunomide and nitrogen mustard. Ball Clin Rheum Rheumatol 1995; 9: 711–29

    Article  CAS  Google Scholar 

  7. Boers M. Renal disorders in rheumatoid arthritis. Semin Arthritis Rheum 1990; 20: 57–68

    Article  PubMed  CAS  Google Scholar 

  8. Boers M, Croonen AM, Dijkmans BAC, et al. Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies. Ann Rheum Dis 1987; 46: 658–63

    Article  PubMed  CAS  Google Scholar 

  9. Boers M, Dijkmans BAC, Breedveld FC, et al. Subclinical renal dysfunction in rheumatoid arthritis. Arthritis Rheum 1990; 33: 95–101

    Article  PubMed  CAS  Google Scholar 

  10. Berg KJ, Forre O, Djoseland O, et al. Renal side effects of high and low cyclosporin A doses in patients with rheumatoid arthritis. Clin Nephrol 1989; 31: 232–8

    PubMed  CAS  Google Scholar 

  11. Boers M, van Rijthoven AWAM, Goei Thè HS, et al. Serum creatinine levels two years later: follow-up of a placebo controlled trial of cyclosporin in rheumatoid patients. Transplant Proc 1988; 20: 371–5

    PubMed  CAS  Google Scholar 

  12. Boers M, Dijkmans BAC, van Rijthoven AWAM, et al. Reversible nephrotoxicity of cyclosporin in rheumatoid arthritis. J Rheumatol 1990; 17: 38–42

    PubMed  CAS  Google Scholar 

  13. Dougados M, Duchesne L, Awada H, et al. Assessment of efficacy and acceptability of low dose cyclosporin in patients with rheumatoid arthritis. Ann Rheum Dis 1989; 48: 550–6

    Article  PubMed  CAS  Google Scholar 

  14. Rijthoven van AWAM, Dijkmans BAC, Goei Thè HS, et al. Comparison of cyclosporin and d-penicillamine for rheumatoid arthritis: a randomized, double blind, multicentre study. J Rheumatol 1991; 18: 815–20

    PubMed  Google Scholar 

  15. Tugwell P, Bombardier C, Gent M, et al. Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis. Lancet 1990; 335: 1051–5

    Article  PubMed  CAS  Google Scholar 

  16. Landewé RBM, Goei Thè HS, van Rijthoven AWAM, et al. A randomized, double blind, 24 week controlled study of low-dose cyclosporin versus chloroquine for early rheumatoid arthritis. Arthritis Rheum 1994; 37: 637–43

    Article  PubMed  Google Scholar 

  17. Mihatsch MJ, Antonovych T, Bohman SO, et al. Cyclosporin A nephropathy; standardization of the evaluation of kidney biopsies. Clin Nephrol 1994; 4: 23–32

    Google Scholar 

  18. Carlesen E, Prydz H. Enhancement of procoagulant activity in stimulated mononuclear blood cells and monocytes by cyclosporin. Transplantation 1987; 43: 543–8

    Article  PubMed  CAS  Google Scholar 

  19. Voss BL, Hamilton KK, Samara EN, McKee PA. Cyclosporin suppression of endothelial prostacyclin generation, a possible mechanism for nephrotoxicity. Transplantation 1988; 45: 793–6

    Article  PubMed  CAS  Google Scholar 

  20. Mason J. The pathophysiology of Sandimmune® (cyclosporin) in man and animals. Pediatr Nephrol 1990; 4: 554–74

    Article  PubMed  CAS  Google Scholar 

  21. Khanna A, Li B, Stenzel KH, et al. Regulation of new DNA synthesis in mammalian cells by cyclosporin. Transplantation 1994; 57: 577–82

    PubMed  CAS  Google Scholar 

  22. Ludwin D, Alexopoulou I, Esdaile JM, et al. Renal biopsy specimens from patients with rheumatoid arthritis and apparently normal renal function after therapy with cyclosporin. Canadian Multicentre Rheumatology Group. Am J Kidney Dis 1994; 23: 260–5

    PubMed  CAS  Google Scholar 

  23. Sund S, FΦrre O, Berg KJ, et al. Morphological and functional renal-effects of low-dose cyclosporin A treatment in patients with rheumatoid arthritis. Clin Nephrol 1994; 41: 33–40

    PubMed  CAS  Google Scholar 

  24. Landewé RBM, Dijkmans BAC, van der Woude FJ, et al. Long term low-dose cyclosporin in patients with rheumatoid arthritis. Renal function loss without structural nephropathy. J Rheumatol 1996; 23: 61–4

    PubMed  Google Scholar 

  25. Rodriquez F, Krayenbuhl JC, Harrison WB, et al. Renal biopsy findings and follow-up of renal function in rheumatoid arthritis patients treated with Cyclosporin A. Arthritis Rheum 1996; 39: 1491–8

    Article  Google Scholar 

  26. Panayi GS, Tugwell P. The use of cyclosporin A in rheumatoid arthritis. Br J Rheumatol 1993; 32Suppl. 1: 1–3

    Google Scholar 

  27. Panayi GS, Tugwell P. The use of cyclosporin A in rheumatoid arthritis: conclusions of an international review. Br J Rheumatol 1994; 33: 967–9

    Article  PubMed  CAS  Google Scholar 

  28. Laasko M, Muntru O, Isomaki H, et al. Cancer mortality in patients with rheumatoid arthritis. J Rheumatol 1986; 13: 522–6

    Google Scholar 

  29. Sela O, Schoenfield Y. Cancer in autoimmune diseases. Semin Arthritis Rheum 1988; 18: 77–87

    Article  PubMed  CAS  Google Scholar 

  30. Arellamo F, Krupp P. Malignancies in rheumatoid arthritis treated with cyclosporin A. Br J Rheumatol 1993; 32Suppl. 1: 72–5

    Google Scholar 

  31. Cockburn ITR, Krupp P. The risk of neoplasm in patients treated with cyclosporin A. J Autoimmun 1989; 2: 723–31

    Article  PubMed  CAS  Google Scholar 

  32. Zijlmans JMJM, van Rijthoven AWAM, Kluin PM, et al. Epstein-Barr-virus associated lymphoma in a patient with rheumatoid arthritis treated with cyclosporin [letter]. N Engl J Med 1992; 326: 1363

    PubMed  CAS  Google Scholar 

  33. Borne van den BEEM, Landewe RBM, Houkes I, et al. No increased risk of malignancies and mortality in cyclosporin A treated rheumatoid arthritis patients. Arthritis Rheum 1998. In press

  34. Kim JH, Perfect JR. Infection and cyclosporin. Rev Infect Dis 1989; 11: 677–90

    Article  PubMed  CAS  Google Scholar 

  35. Dawson T, Ryan PFJ, Findeisen JM, et al. Pneumocystis carinii pneumonia following cyclosporin A and methotrexate treated rheumatoid arthritis. Correspondence. J Rheumatol 1992; 19: 997

    PubMed  CAS  Google Scholar 

  36. Ferraccioli GF, Casatta L, Bartoli E, et al. Epstein-Barr virus associated Hodgkin’s lymphoma in a rheumatoid arthritis patient treated with methotrexate and cyclosporin A. Arthritis Rheum 1995; 38: 867–8

    Article  PubMed  CAS  Google Scholar 

  37. Cohen DJ, Appel GB. Cyclosporin: nephrotoxic effects and guidelines for safe use in patients with rheumatoid arthritis. Semin Arthritis Rheum 1992; 21Suppl. 3: 43–8

    Article  PubMed  CAS  Google Scholar 

  38. Lin HY, Rocher LI, McQuillan MA, et al. Cyclosporin-induced hyperuricaemia and gout. N Engl J Med 1989; 321: 287–92

    Article  PubMed  CAS  Google Scholar 

  39. Ioannides-Demos LL, Christophidis N, Ryan P, et al. Dosing implications of a clinical interaction between grapefruit juice and cyclosporin and metabolite concentrations in patients with autoimmune diseases. J Rheumatol 1997; 24: 49–54

    PubMed  CAS  Google Scholar 

  40. Kovarik JH, Kurki P, Mueller E, et al. Diclofenac combined with cyclosporin in the treatment of refractory rheumatoid arthritis. Longitudinal safety assessment and evidence of a pharmacokinetic/dynamic interaction. J Rheumatol 1996; 23: 2033–8

    PubMed  CAS  Google Scholar 

  41. Altman RD, Perez GO, Sfakianakis GN. Interaction of cyclosporin A and nonsteroidal anti-inflammatory drugs on renal function in patients with rheumatoid arthritis. Am J Med 1992; 93: 396–402

    Article  PubMed  CAS  Google Scholar 

  42. Furst DE. Clinical pharmacology of combination DMARD therapy in rheumatoid arthritis. J Rheumatol 1996; 23Suppl. 44: 86–90

    Google Scholar 

  43. Salaffi F, Carotti M, Cervini C. Combination therapy of cyclosporin A with methotrexate or hydroxychloroquine in refractory rheumatoid arthritis. Scand J Rheumatol 1996; 25: 16–23

    Article  PubMed  CAS  Google Scholar 

  44. Bensen W, Tugwell P, Roberts RM, et al. Combination therapy of cyclosporin with methotrexate and gold in rheumatoid arthritis (2 pilot studies). J Rheumatol 1994; 21: 2034–8

    PubMed  CAS  Google Scholar 

  45. Tugwell P, Pincus T, Yocum D, et al. Combination therapy with cyclosporin and methotrexate in severe rheumatoid arthritis. N Engl J Med 1995; 333: 137–41

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ben Dijkmans.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dijkmans, B., Gerards, A. Cyclosporin in Rheumatoid Arthritis. BioDrugs 10, 437–445 (1998). https://doi.org/10.2165/00063030-199810060-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-199810060-00002

Keywords

Navigation