Abstract
Tacrolimus (FK506) ointment is widely used in the treatment of patients with atopic dermatitis. The drug exerts its action by down-regulating antigen-specific T-cell activities and associated proinflammatory cytokine production. A number of clinical studies have evaluated the efficacy and safety of 0.1% tacrolimus ointment compared with vehicle or topical corticosteroids in adult patients with atopic dermatitis. These studies have suggested that topical tacrolimus has a rapid onset of action and exerts sustained therapeutic effects, with an efficacy similar to that of moderate to potent topical corticosteroids, but without causing skin atrophy. Two phase III randomised, controlled clinical trials have been conducted in Japanese adult patients with atopic dermatitis to compare the efficacy and safety of topical 0.1% tacrolimus with topical corticosteroid ointments. In the first study, patients with moderate or severe atopic dermatitis on the trunk and extremities were randomised to 3 weeks of treatment with topical 0.1% tacrolimus or the mid-potency topical corticosteroid 0.12% betamethasone valerate. Over 90% of the patients in each study group experienced at least a moderate improvement at the end of the study. In the second study, patients with moderate or severe atopic dermatitis on the head or neck were randomised to 1 week of treatment with 0.1% tacrolimus or the mild-potency corticosteroid 0.1% alclometasone dipropionate. Significantly greater improvements in individual symptom scores were observed with topical tacrolimus compared with alclometasone dipropionate, with overall global improvement at 1 week being statistically superior with tacrolimus. Furthermore, in a long-term open-label study involving 568 patients, at least a moderate global improvement in symptoms was observed in 85% of patients at 6 weeks, increasing to 91% at both 26 weeks and 52 weeks; this rate was maintained throughout the 2-year duration of the study. 0.1% tacrolimus ointment was considered to be safe in the majority of patients. The most prevalent adverse reactions were local application site irritations, which generally resolved with continued therapy. In summary, these findings suggest that 0.1% tacrolimus ointment is an effective and safe nonsteroidal alternative therapy for adult patients with atopic dermatitis.
Similar content being viewed by others
Notes
The use of trade names is for product identification purposes only and does not imply endorsement.
References
Thomson AW, Bonham CA, Zeevi A. Mode of action of tacrolimus (FK506): molecular and cellular mechanisms. Ther Drug Monit 1995; 17(6): 584–91
Hultsch T, Brand P, Lohmann S, et al. Direct evidence that FK506 inhibition of FcepsilonRI-mediated exocytosis from RBL mast cells involves calcineurin. Arch Dermatol Res 1998; 290(5): 258–63
Panhans-Gross A, Novak N, Kraft S, et al. Human epidermal Langerhans’ cells are targets for the immunosuppressive macrolide tacrolimus (FK506). J Allergy Clin Immunol 2001; 107(2): 345–52
Mori A, Suko M, Nishizaki Y, et al. Regulation of interleukin-5 production by peripheral blood mononuclear cells from atopic patients with FK506, cyclosporin A and glucocorticoid. Int Arch Allergy Immunol 1994; 104Suppl 1 (1): 32–5
Goto T, Kino T, Hatanaka H, et al. Discovery of FK-506, a novel immunosuppressant isolated from Streptomyces tsukubaensis. Transplant Proc 1987; 19(5 Suppl. 6): 4–8
Dumont FJ, Staruch MJ, Koprak SL, et al. Distinct mechanisms of suppression of murine T cell activation by the related macrolides FK-506 and rapamycin. J Immunol 1990; 144(1): 251–8
Dumont FJ, Staruch MJ, Fischer P, et al. Inhibition of T cell activation by pharmacologic disruption of the MEK1/ERK MAP kinase or calcineurin signaling pathways results in differential modulation of cytokine production. J Immunol 1998; 160(6): 2579–89
Leung DY, Boguniewicz M, Howell MD, et al. New insights into atopic dermatitis. J Clin Invest 2004; 113(5): 651–7
Wollenberg A, Sharma S, von Bubnoff D, et al. Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis. J Allergy Clin Immunol 2001; 107(3): 519–25
dePaulis A, Stellate C, Cirillo R, et al. Anti-inflammatory effect of FK-506 on human skin mast cells. J Invest Dermatol 1992; 99(6): 723–8
Leung DY, Nicklas RA, Li JT, et al. Disease management of atopic dermatitis: an updated practice parameter. Joint Task Force on Practice Parameters. Ann Allergy Asthma Immunol 2004; 93(3 Suppl. 2): S1–21
Leung DY, Bieber T. Atopic dermatitis. Lancet 2003; 361(9352): 151–60
Grewe M, Bruijnzeel-Koomen CA, Schopf E, et al. A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis. Immunol Today 1998; 19(8): 359–61
FK506 Ointment Study Group. Late phase II concentration-finding study of FK506 (tacrolimus) ointment in atopic dermatitis (part 1). Nishinihon J Derm (Japanese) 1998; 60(5): 685–98
FK506 Ointment Study Group. Late phase II concentration-finding study of FK506 (tacrolimus) ointment in atopic dermatitis (part 2). Nishinihon J Derm (Japanese) 1997; 59(3): 427–35
Lubach D, Bensmann A, Bornemann U. Steroid-induced dermal atrophy: investigations on discontinuous application. Dermatologica 1989; 179(2): 67–72
Furue M, Terao H, Rikihisa W, et al. Clinical dose and adverse effects of topical steroids in daily management of atopic dermatitis. Br J Dermatol 2003; 148(1): 128–33
Vie R. Glaucoma and amaurosis associated with long-term application of topical corticosteroids to the eyelids. Acta Derm Venereol 1980; 60(6): 541–2
Matsuda K, Katsunuma T, Iikura Y, et al. Adrenocortical function in patients with severe atopic dermatitis. Ann Allergy Asthma Immunol 2000; 85(1): 35–9
Ruiz-Maldonado R, Zapata G, Lourdes T, et al. Cushing’s syndrome after topical application of corticosteroids. Am J Dis Child 1982; 136(3): 274–5
FK506 Ointment Study Group. Phase III comparative study of FK506 ointment. Group comparison study with betamethasone valerate in atopic dermatitis: trunk and extremities. Nishinihon J Derm (Japanese) 1997; 59(3): 870–9
FK506 Ointment Study Group. Phase III comparative study of FK506 ointment. Group comparison study with alclometasone dipropionate in atopic dermatitis: face and neck. Acta Dermatologica (Kyoto) (Japanese) 1997; 92(3): 277–88
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol 1980; 92 Suppl.: 22–47
Rajka G, Langeland T. Grading of the severity of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 1989; 144: 13–4
FK506 Ointment Study Group. Long-term study of FK506 (tacrolimus) ointment in patients with atopic dermatitis -analysis at time of completion of 2-year observation. J Clin Ther Med (Japanese) 2001; 17(5): 705–26
Kawashima M. Quality of life in patients with atopic dermatitis: impact of tacrolimus ointment. In J Derm 2006; 45 (6). In press
Hanifin JM. Pharmacophysiology of atopic dermatitis. Clin Rev Allergy 1986; 4(1): 43–65
Dimson S, Nanayakkara C. Do oral antihistamines stop the itch of atopic dermatitis? Arch Dis Child 2003; 88(9): 832–3
Otsuki M, Nakagawa H, Kawashima M, et al. Efficacy and safety of FK506 (tacrolimus) ointment in children with atopic dermatitis: phase III double-blinded comparison with vehicle ointment. J Clin Ther Med (Japanese) 2003; 19(6): 569–95
Katoh N, Hirano S, Yasuno H, et al. Effects of tacrolimus ointment on facial eruption, itch, and scratching in patients with atopic dermatitis. J Dermatol 2004; 31(3): 194–9
Toyoda M. Antipruritic mechanism of tacrolimus ointment for atopic dermatitis: consideration of dermatoneuronal factors. Clin Dermatol (Japanese) 2003; 57(5): 45–50
Hanifin JM, Ling MR, Langley R, et al. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part I, efficacy. J Am Acad Dermatol 2001; 44(1 Suppl.): S28–38
Pacor ML, Di Lorenzo G, Martinelli N, et al. Comparing tacrolimus ointment and oral cyclosporine in adult patients affected by atopic dermatitis: a randomized study. Clin Exp Allergy 2004; 34(4): 639–45
Palier AS, Lebwohl M, Fleischer Jr AB, et al. 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 2005; 52(5): 810–22
Reitamo S, VanLeent EJ, Ho V, et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate ointment in children with atopic dermatitis. J Allergy Clin Immunol 2002; 109(3): 539–46
Ruzicka T, Bieber T, Schopf E, et al. A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group. N Engl J Med 1997; 337(12): 816–21
Reitamo S, Rustin M, Ruzicka T, et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis. J Allergy Clin Immunol 2002; 109(3): 547–55
Simpson D, Noble S. Tacrolimus ointment: a review of its use in atopic dermatitis and its clinical potential in other inflammatory skin conditions. Drugs 2005; 65(6): 827–58
Hanifin JM, Palier AS, Eichenfield L, et al. Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis. J Am Acad Dermatol 2005; 53(2 Suppl. 2): S186–94
Reitamo S, Ortonne JP, Sand C, et al. 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 2005; 152(6): 1282–9
Reitamo S. Quality of life improved in adults with moderate to severe atopic dermatitis with 0.1% tacrolimus ointment [abstract plus poster]. Congress of the European Academy of Dermatology and Venereology; 2004 29 Apr-1 May; Budapest, Hungary
FleischerJr AB, Ling M, Eichenfield L, et al. Tacrolimus ointment for the treatment of atopic dermatitis is not associated with an increase in cutaneous infections. J Am Acad Dermatol 2002; 47(4): 562–70
Soter NA, FleischerJr AB, Webster GF, et al. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety. J Am Acad Dermatol 2001; 44(1 Suppl.): S39–46
Koo JY, FleischerJr AB, Abramovits W, et al. Tacrolimus ointment is safe and effective in the treatment of atopic dermatitis: results in 8000 patients. J Am Acad Dermatol 2005; 53(2 Suppl. 2): S195–205
Reitamo S, Wollenberg A, Schopf E, et al. 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(8): 999–1006
Kikuchi K, Tagami H. Comparison of the effects of daily applications between topical corticosteroid and tacrolimus ointments on normal skin: evaluation with noninvasive methods. Dermatology 2002; 205(4): 378–82
Kyllonen H, Remitz A, Mandelin JM, et al. Effects of 1-year intermittent treatment with topical tacrolimus monotherapy on skin collagen synthesis in patients with atopic dermatitis. Br J Dermatol 2004; 150(6): 1174–81
Fonacier L, Spergel J, Charlesworth EN, et al. 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 2005; 115(6): 1249–53
Naylor M, Elmets C, Jaracz E, et al. Non-melanoma skin cancer in patients with atopic dermatitis treated with topical tacrolimus. J Dermatolog Treat 2005; 16(3): 149–53
Stiehm ER, Roberts RL, Kaplan MS, et al. Pneumococcal seroconversion after vaccination for children with atopic dermatitis treated with tacrolimus ointment. J Am Acad Dermatol 2005; 53(2 Suppl. 2): S206–13
Acknowledgements
This review received no external funding, and the authors have no conflicts of interest relating to the contents of this review.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nakagawa, H. Comparison of the Efficacy and Safety of 0.1% Tacrolimus Ointment with Topical Corticosteroids in Adult Patients with Atopic Dermatitis. Clin. Drug Investig. 26, 235–246 (2006). https://doi.org/10.2165/00044011-200626050-00001
Published:
Issue Date:
DOI: https://doi.org/10.2165/00044011-200626050-00001