Topical tacrolimus in atopic dermatitis: Effects of ... - Helda - Helsinki.fi

extent of topical absorption decrease as skin lesions heal (Rubins et al. 2005). These
findings suggest that tacrolimus ointment is safe in long-term treatment.
In systemic use, tacrolimus is immunosuppressive and possibly associated with
increased cancer, especially lymphoma, risk. Topical tacrolimus associated with nonmelanoma
skin cancer in a mouse model (Niwa et al. 2003). In the USA, this led to
black box warnings on increased cancer risk from topical tacrolimus and pimecrolimus.
However, a recent large case-control study with a cohort of over 290 000 patients
receiving different AD treatments found no increased risk for lymphoma in patients
treated with topical calcineurin inhibitors, the main factor associated with increased
lymphoma risk being AD severity (Arellano et al. 2006). According to a recent systemic
review on topical treatment of AD, significant local or systemic adverse events are
mainly associated with use of topical corticosteroids (Callen et al. 2007).
Tacrolimus ointment - Monotherapy and maintenance therapy
Tacrolimus ointment is currently indicated for moderate-to-severe AD as an intermittent
treatment. Results of intermittent or continuous monotherapy in long-term studies have
been good (Reitamo et al. 2000, Kang et al. 2001, Hanifin et al. 2005, Remitz et al.
2007). Because tacolimus is a relatively new compound and more expensive than
topical corticosteroids, attempts have been made to combine it with topical
corticosteroids. One study suggested that when tacrolimus ointment is used only on
facial AD, and the other AD areas are treated with corticosteroids, the long-term results
are poor despite a favorable initial response (Sugiura et al. 2000). These results
correlated inversely with the AD severity and amount of corticosteroids. Recent as-yet
unpublished studies in adults and children on maintenance therapy with tacrolimus
ointment twice weekly after an initial treatment period twice daily for up to 6 weeks
suggest that long-term control of AD can be achieved with fewer relapses and with
reasonable use of tacrolimus ointment (EADV congress 2007, Rhodes). Similar results
with potent corticosteroid compounds are published (Berth-Jones et al. 2003,
Faergemann et al. 2000, Hanifin et al. 2002). Comparative studies with tacrolimus and
corticosteroids in maintenance therapy are thus far lacking.
Pimecrolimus cream
Pimecrolimus is the other topical calcineurin inhibitor developed during the same period
as tacrolimus. Pimecrolimus 1% cream is licenced for mild to moderate AD in adults
and children. The drug molecule is very similar to tacrolimus but somewhat more
lipophilic. It has an affinity one- third of that of tacrolimus to their common carrier
protein FKBP12. Pimecrolimus cream has shown superior efficacy to its vehicle but is
weaker than betamethasone (Luger et al. 2001). A long-term, randomized, controlled
study with tricamcinolone acetate on the body and extremities, with hydrocortisone
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