| アブストラクト | BACKGROUND: There is a concern that topical tacrolimus and pimecrolimus, indicated for second-line treatment of atopic dermatitis, may increase the risk of lymphoma and skin cancer, particularly in children. OBJECTIVE: The aim of this study was to compare incidence rates (IRs) of lymphoma and skin cancer between new users of topical tacrolimus or pimecrolimus and users of moderate- to high-potency topical corticosteroids (TCSs) and untreated subjects. METHODS: This is a multicenter cohort study with frequency matching by strata of propensity scores in population databases in the Netherlands, Denmark, Sweden, and the UK. IR ratios (IRRs) were estimated using Mantel-Haenszel methods for stratified analysis. RESULTS: We included 19,948 children and 66,127 adults initiating tacrolimus, 23,840 children and 37,417 adults initiating pimecrolimus, 584,121 users of TCSs, and 257,074 untreated subjects. IRs of lymphoma per 100,000 person-years were 10.4 events in children and 41.0 events in adults using tacrolimus and 3.0 events in children and 27.0 events in adults using pimecrolimus. The IRR (95% confidence interval [CI]) for lymphoma, tacrolimus versus TCSs, was 3.74 (1.00-14.06) in children and 1.27 (0.94-1.71) in adults. By lymphoma type, the highest IRR was 3.17 (0.58-17.23) for Hodgkin lymphoma in children and 1.76 (95% CI, 0.81-3.79) for cutaneous T-cell lymphoma (CTCL) in adults. For pimecrolimus versus TCSs, the highest IRR was 1.31 (95% CI, 0.33-5.14) for CTCL in adults. Compared with untreated subjects, adults using TCSs had a higher incidence of CTCL (IRR, 10.66; 95% CI, 2.60-43.75). Smaller associations were found between tacrolimus and pimecrolimus use and the risk of malignant melanoma or nonmelanoma skin cancer. CONCLUSION: Use of topical tacrolimus and pimecrolimus was associated with an increased risk of lymphoma. The low IRs imply that even if the increased risk is causal, it represents a small excess risk for individual patients. Residual confounding by severity of atopic dermatitis, increased monitoring of severe patients, and reverse causation could have affected the results. |
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| ジャーナル名 | Clinical epidemiology |
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| 投稿日 | 2018/3/22 |
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| 投稿者 | Castellsague, Jordi; Kuiper, Josephina G; Pottegard, Anton; Anveden Berglind, Ingegard; Dedman, Daniel; Gutierrez, Lia; Calingaert, Brian; van Herk-Sukel, Myrthe Pp; Hallas, Jesper; Sundstrom, Anders; Gallagher, Arlene M; Kaye, James A; Pardo, Carolina; Rothman, Kenneth J; Perez-Gutthann, Susana |
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| 組織名 | Department of Epidemiology, RTI Health Solutions, Barcelona, Spain.;Department Research, PHARMO Institute for Drug Outcomes Research, Utrecht, the;Netherlands.;Clinical Pharmacology and Pharmacy, Department of Public Health, University of;Southern Denmark, Odense, Denmark.;Centre for Pharmacoepidemiology, Unit of Clinical Epidemiology, Department of;Medicine, Karolinska Institutet, Stockholm, Sweden.;Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory;Agency, London, UK.;Department Epidemiology, RTI Health Solutions, Research Triangle Park, NC.;Department of Epidemiology, RTI Health Solutions, Waltham, MA, USA.;Pharmacovigilance Department, Astellas Pharma Europe B.V., Leiden, the |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/29559812/ |
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