Abstract
In the present study, we retrospectively evaluate the efficacy of low dose tacrolimus (TAC) as add-on therapy in refractory rheumatoid arthritis (RA) despite a combination of tumor necrosis factor (TNF) inhibitor and methotrexate (MTX) using consecutive case series of five patients with active RA (mean disease duration 2.3 years) despite MTX and TNF inhibitors for at least 3 months (mean 9.5 months) treated with low dose TAC (1.5–2 mg/day) for at least 6 months (mean 1.8 years). Clinical and radiographic efficacy was assessed according to the European league against rheumatism response criteria and the modified Sharp method, respectively. At 1 year, three patients reached to remission. The mean yearly progression of radiographic joint damage of all five patients after the onset of TAC was significantly decreased compared to that observed during anti-TNF therapy without TAC (p = 0.04). One patient temporally discontinued the treatment because of herpes zoster. In RA patients with inadequate response to MTX and a TNF inhibitor, additions of low dose TAC markedly improved clinical variables including radiographic scores without remarkable detrimental effects. It seems that TAC in combination with MTX and TNF inhibitors may be a hopeful treatment option for RA patients with inadequate response to anti-TNF therapy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM et al (2005) Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 52:3381–3390. doi:10.1002/art.21405
Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D et al (2008) Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet 372:375–382. doi:10.1016/S0140-6736(08)61000-4
Kino T, Hatanaka H, Miyata S, Inamura N, Nishiyama M, Yajima T et al (1987) FK-506, a novel immunosuppressant isolated from a Streptomyces. II: immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo) 40:1256–1265
Kondo H, Abe T, Hashimoto H, Uchida S, Irimajiri S, Hara M et al (2004) Efficacy and safety of tacrolimus (FK506) in treatment of rheumatoid arthritis: a randomized, double blind, placebo controlled dose-finding study. J Rheumatol 31:243–251
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324. doi:10.1002/art.1780310302
Prevoo ML, van‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48. doi:10.1002/art.1780380107
Pincus T, Summey JA, Soraci SA Jr, Wallston KA, Hummon NP (1983) Assessment of patient satisfaction in activities of daily living using a modified Stanford health assessment questionnaire. Arthritis Rheum 26:1346–1353. doi:10.1002/art.1780261107
van der Heijde D (2000) How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 27:261–263
van Gestel AM, Prevoo ML, van‘t Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL (1996) Development and validation of the European League against Rheumatism response criteria for rheumatoid arthritis: comparison with the preliminary American College of Rheumatology and the World Health Organization/International League against Rheumatism Criteria. Arthritis Rheum 39:34–40. doi:10.1002/art.1780390105
Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR et al (2008) American College of Rheumatology. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 59:762–784. doi:10.1002/art.23721
Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, et al (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-TNF biologics: results from a 24-week multicentre randomised placebo controlled trial. Ann Rheum Dis published online first 14. doi:10.1136/ard.2008.092932
Ferraccioli GF, Assaloni R, Di Poi E, Gremese E, De Marchi G, Fabris M (2002) Rescue of combination therapy failures using infliximab, while maintaining the combination or monotherapy with methotrexate: results of an open trial. Rheumatol (Oxf) 41:1109–1112. doi:10.1093/rheumatology/41.10.1109
Sidiropoulos PI, Siakka P, Raptopoulou A, Mamoulaki M, Choulaki C, Koutala H et al (2006) An open label, single dose study to evaluate the safety, efficacy, and effects on CD25 expression of ciclosporin in patients with active rheumatoid arthritis despite treatment with methotrexate and infliximab. Ann Rheum Dis 65:538–541. doi:10.1136/ard.2005.036152
Kremer JM, Habros JS, Kolba KS, Kaine JL, Borton MA, Mengle-Gaw LJ et al (2003) Tacrolimus in rheumatoid arthritis patients receiving concomitant methotrexate: a six-month, open-label study. Arthritis Rheum 48:2763–2768. doi:10.1002/art.11257
Tugwell P, Pincus T, Yocum D, Stein M, Gluck O, Kraag G et al (1995) Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis: the Methotrexate-Cyclosporine Combination Study Group. N Engl J Med 333:137–141. doi:10.1056/NEJM199507203330301
Conflict of interest statement
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Naniwa, T., Watanabe, M., Banno, S. et al. Adding low dose tacrolimus in rheumatoid arthritis patients with an inadequate response to tumor necrosis factor inhibitor therapies. Rheumatol Int 29, 1287–1291 (2009). https://doi.org/10.1007/s00296-009-0845-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-009-0845-3