Safety of topical calcineurin inhibitors in atopic dermatitis: Evaluation of the evidence
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Topical calcineurin inhibitors (pimecrolimus, Elidel, East Hanover, NJ; and tacrolimus, Protopic, Tokyo, Japan) have been approved for the use in atopic dermatitis since the year 2000. These compounds represent a relatively safe class of topical anti-inflammatory, nonsteroidal therapy. However, in January of 2006, the US Food and Drug Administration issued a black box warning on these compounds about possible concerns of increased long-term malignancy risk due to systemic immunosuppression. To date, studies from clinical trials, systemic absorption, and post-marketing surveillance show no evidence for this systemic immunosuppression or increased risk for any malignancy.
- Taieb, A, Hanifin, J, Cooper, K (2006) Proceedings of the 4th Georg Rajka International Symposium on Atopic Dermatitis, Arcachon, France, September 15–17, 2005. J Allergy Clin Immunol 117: pp. 378-390 CrossRef
- Grassberger, M, Baumruker, T, Enz, A (1999) A novel antiin flammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol 141: pp. 264-273 CrossRef
- Leent, EJ, Ebelin, ME, Burtin, P (2002) Low systemic exposure after repeated topical application of pimecrolimus (Elidel), SD Z ASM 981) in patients with atopic dermatitis. Dermatology 204: pp. 63-68 CrossRef
- Hultsch, T, Kapp, A, Spergel, J (2005) Immunomodulation and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis. Dermatology 211: pp. 174-187 CrossRef
- Wellington, K, Jarvis, B (2002) Topical pimecrolimus: a review of its clinical potential in the management of atopic dermatitis. Drugs 62: pp. 817-840 CrossRef
- Luger, T, Leent, EJ, Graeber, M (2001) SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis. Br J Dermatol 144: pp. 788-794 CrossRef
- Eichenfield, L, Lucky, A, Boguniewicz, M (2002) Safety and Efficacy of pimecrolimus (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents. J Am Acad Dermatol 46: pp. 495-504 CrossRef
- Paller, AS, Lebwohl, M, Fleischer, AB Jr (2005) Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: results from 3 randomized, comparative studies. J Am Acad Dermatol 52: pp. 810-822 CrossRef
- Boguniewicz, M, Fiedler, VC, Raimer, S (1998) A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group. J Allergy Clin Immunol 102: pp. 637-644 CrossRef
- Ruzicka, T, Bieber, T, Schopf, E, F, (1997) A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group. N Engl J Med 337: pp. 816-821 CrossRef
- Paller, AS, McAlister, RO, Doyle, JJ, Jackson, A (2002) Perceptions of physicians and pediatric patients about atopic dermatitis, its impact, and its treatment. Clin Pediatr (Phila) 41: pp. 323-332 CrossRef
- Staab, D, Kaufmann, R, Brautigam, M, Wahn, U (2005) Treatment of infants with atopic eczema with pimecrolimus cream 1% improves parents’ quality of life: a multicenter, randomized trial. Pediatr Allergy Immunol 16: pp. 527-533 CrossRef
- Drake, L, Prendergast, M, Maher, R (2001) The impact of tacrolimus ointment on health-related quality of life of adult and pediatric patients with atopic dermatitis. J Am Acad Dermatol 44: pp. S65-S72 CrossRef
- Fonacier, L, Spergel, J, Charlesworth, EN (2005) Report of the Topical Calcineurin Inhibitor Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 115: pp. 1249-1253 CrossRef
- Novartis-Pharmeutical: Elidel prescribing information. (@#@ Package insert): 2006.
- Astellas-Pharmaceutical: Protopic prescribing information. (@#@ Package insert): 2006.
- Allen, B, Lakhanpaul, M, Morris, A (2003) Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients. Arch Dis Child 88: pp. 969-973 CrossRef
- Harper, J, Green, A, Scott, G (2001) First experience of topical SDZ ASM 981 in children with atopic dermatitis. Br J Dermatol 144: pp. 781-787 CrossRef
- Harper, J, Smith, C, Rubins, A (2005) A multicenter study of the pharmacokinetics of tacrolimus ointment after .rst and repeated application to children with atopic dermatitis. J Invest Dermatol 124: pp. 695-699 CrossRef
- Pediatric Advisory Committee Meeting of the US Food Drug Administration. http://www.fda.gov/ohrms/dockets/ ac/05/brie.ng/2005-4089b2.htm The site provides the complete hearing of the FDA pediatric advisory committee on the topical calcineurin inhbitors.20. Novartis-Pharmaceutical. Data on .le; 2006.
- Astellas-Pharmaceutical: Data on .le: 2006.
- SEER cancer statistics review, 1975–2001. http://seer. cancer.gov/csr/1975_2001/.
- Hill, DJ, Sporik, R, Thorburn, J, Hosking, CS (2000) The association of atopic dermatitis in infancy with immunoglobulin E food sensitization. J Pediatr 137: pp. 475-479 CrossRef
- Naylor, M, Elmets, C, Jaracz, E, Rico, JM (2005) Non-melanoma skin cancer in patients with atopic dermatitis treated with topical tacrolimus. J Dermatol Treat 16: pp. 149-153 CrossRef
- Miller, D, Weinstock, M (1995) Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol 30: pp. 774-778 CrossRef
- Tran, C, Lubbe, J, Sorg, O (2005) Topical calcineurin inhibitors decrease the production of UVB-induced thymine dimers from hairless mouse epidermis. Dermatology 211: pp. 341-347 CrossRef
- Papp, KA, Breuer, K, Meurer, M (2005) Long-term treatment of atopic dermatitis with pimecrolimus cream 1% in infants does not interfere with the development of protective antibodies after vaccination. J Am Acad Dermatol 52: pp. 247-253 CrossRef
- Stiehm, ER, Roberts, RL, Kaplan, MS (2005) Pneumococcal seroconversion after vaccination for children with atopic dermatitis treated with tacrolimus ointment. J Am Acad Dermatol 53: pp. S206-S213 CrossRef
- Packet insert: Protopic (tacrolimus 0.03 and 0.1%) ointment. Rockville, MD: US Food and Drug Administration.
- Wahn, U, Bos, JD, Goodfield, M (2002) Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics 110: pp. e2-e2 CrossRef
- Ringer, Ellingsen A, Brandt, Sorensen F, Overgaard, Larsen J (2001) Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients. Acta Dermatol Venereol 81: pp. 258-262 CrossRef
- Hanifin, JM, Paller, AS, Eichenfield, L (2005) Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis. J Am Acad Dermatol 53: pp. S186-S194 CrossRef
- Reitamo, S, Ortonne, JP, Sand, C (2005) A multicentre, randomized, double-blind, controlled study of long-term treatment with 0.1% tacrolimus ointment in adults with moderate to severe atopic dermatitis. Br J Dermatol 152: pp. 1282-1289 CrossRef
- Paul, C, Cork, M, Rossi, AB (2006) Safety and tolerability of 1% pimecrolimus cream among infants: experience with 1133 patients treated for up to 2 years. Pediatrics 117: pp. e118-e128 CrossRef
- Safety of topical calcineurin inhibitors in atopic dermatitis: Evaluation of the evidence
Current Allergy and Asthma Reports
Volume 6, Issue 4 , pp 270-274
- Cover Date
- Print ISSN
- Online ISSN
- Current Medicine Group
- Additional Links
- Industry Sectors