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Vol. 219, No. 1, 2009
Issue release date: June 2009
Dermatology 2009;219:7–21

Topical Treatments with Pimecrolimus, Tacrolimus and Medium- to High-Potency Corticosteroids, and Risk of Lymphoma

Schneeweiss S. · Doherty M. · Zhu S. · Funch D. · Schlienger R.G. · Fernandez-Vidaurre C. · Seeger J.D.
aDepartment of Epidemiology, Harvard School of Public Health, Boston, Mass., bi3 Drug Safety, Waltham, Mass., and cGlobal Clinical Epidemiology, Novartis Pharmaceuticals, East Hanover, N.J., USA; dGlobal Clinical Epidemiology, Novartis Pharma AG, Basel, Switzerland

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Background/Aims: A potential risk of lymphoma associated with the use of topical calcineurin inhibitors is debated. We assessed the risk of lymphoma among patients treated with topical pimecrolimus, tacrolimus or corticosteroids. Methods: We conducted a cohort study using health insurance claims data. Cohorts of initiators of topical pimecrolimus, tacrolimus and corticosteroids, along with cohorts of persons with untreated dermatitis and randomly sampled enrollees were identified from January 2002 to June 2006. Lymphomas were identified using insurance claims and adjudicated by medical records review. We adjusted for confounders by propensity score matching. Results: Among 92,585 pimecrolimus initiators contributing 121,289 person-years of follow-up, we identified 26 lymphomas yielding an incidence of 21/100,000 person-years. This incidence of lymphoma was similar to that among tacrolimus users (rate ratio, RR = 1.16; 95% confidence interval, CI = 0.74–1.82) as well as corticosteroid users (RR = 1.15; 95% CI = 0.49–2.72). All three topical treatments were associated with an increased risk of lymphoma compared with the general population (RRPim = 2.89; RRTac = 2.82; RRCort = 2.10) suggesting increased detection of preexisting lymphomas. Conclusion: This study did not find an increased risk of lymphoma among initiators of topical pimecrolimus relative to other topical agents during an average follow-up of 1.3 years. Longer-term studies may be needed.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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  1. Breuer K, Werfel T, Kapp A: Safety and efficacy of topical calcineurin inhibitors in the treatment of childhood atopic dermatitis. Am J Clin Dermatol 2005;6:65–77.
  2. Reitamo S, Wollenberg A, Schopf E, Perrot JL, Marks R, Ruzicka T, Christophers E, Kapp A, Lahfa M, Rubins A, Jablonska S, Rustin M: Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. The European Tacrolimus Ointment Study Group. Arch Dermatol 2000;136:999–1006.
  3. Won CH, Seo PG, Park YM, Yang JM, Lee KH, Sung KJ, Park CW, Kim DW, Chang HS, Won YH, Kim KH: A multicenter trial of the efficacy and safety of 0.03% tacrolimus ointment for atopic dermatitis in Korea. J Dermatol Treat 2004;15:30–34.
  4. FDA Public Health Advisory. (accessed January 22, 2008).
  5. Langley RG, Luger TA, Cork MJ, Schneider D, Paul C: An update on the safety and tolerability of pimecrolimus cream 1%: evidence from clinical trials and post-marketing surveillance. Dermatology 2007;215:27–44.
  6. Arellano FM, Wentworth CE, Arana A, Fernández C, Paul CF: Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. J Invest Dermatol 2007;127:808–816.
  7. US National Psoriasis Foundation: Potencies of topical steroids. (accessed January 22, 2008).
  8. Gu XS, Rosenbaum PR: Comparison of multivariate matching methods: structures, distances, and algorithms. J Comp Graphical Stat 1993;2:405–420.

    External Resources

  9. Rosenbaum PR, Rubin DB: The central role of the propensity score in observational studies for causal effects. Biometrika 1983;70:41–55.

    External Resources

  10. Rothman KJ, Greenland S: Modern Epidemiology, ed 2. Philadelphia, Lippincott, Williams & Wilkins, 1998.
  11. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ: Cancer statistics, 2007. CA Cancer J Clin 2007;57:43–66.
  12. Hagstroemer L, Weimin Y, Nyren O, Emtestam L: Incidence of cancer among patients with atopic dermatitis. Arch Dermatol 2005; 141:1123–1127.
  13. Zhang Y, Holford TR, Leaderer B, Zahm SH, Boyle P, Morton LM, Zhang B, Zou K, Flynn S, Tallini G, Owens PH, Zheng T: Prior medical conditions and medication use and risk of non-Hodgkin lymphoma in Connecticut United States women. Cancer Causes Control 2004;15:419–428.
  14. Doody MM, Linet MS, Glass AG, Friedman GD, Pottern LM, Boice JD Jr, Fraumeni JF Jr: Leukemia, lymphoma, and multiple myeloma following selected medical conditions. Cancer Causes Control 1992;3:449–456.
  15. Kelsey JL, Whittemore AS, Evans AS, Thompson WD: Methods in Observational Epidemiology, ed 2. New York, Oxford University Press, 1996, pp 341–390.
  16. Freiman JA, Chalmers TC, Smith H Jr, Kuebler RR: The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trial. Survey of 71 ‘negative’ trials. N Engl J Med 1978;299:690–694.
  17. Goodman SN, Berlin JA: The use of predicted confidence intervals when planning experiments and the misuse of power when interpreting results. Ann Intern Med 1994;121:200–206.

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