Table 1.
Summary statements from review articles that assess TCI lymphoma riska
| Citation | Evidence of lymphoma risk with TCIs? | Lymphoma risk summary statement | |
|---|---|---|---|
| Yes | No | ||
| Berger 2006 [18] | √ | …no causal proof that TCIs cause lymphoma… | |
| Deleuran 2009 [19] | √ | …no studies support that the use of topical immunosuppression increases the risk of local or systemic cancerb. | |
| Ehrchen 2008 [20] | √ | …no data indicating that topical therapy in humans results in an increased risk for lymphomas. | |
| Fonacier 2005 [21] | √ | …risk/benefit ratios of topical pimecrolimus and tacrolimus are similar to those of most conventional therapies… | |
| Langley 2007 [22] | √ | …there is no clinical evidence to establish that treatment with pimecrolimus cream 1 % increases the risk of malignancy. | |
| Lebwohl 2006 [23] | √ | …no causal relationship between the use of TCIs and the occurrence of lymphoma… | |
| Legendre 2015 [24] | √ | …systematic literature review shows slightly increased risk of lymphoma in patients with AD…role of topical steroids and TCIs is unlikely to be significant. | |
| McNeill 2007 [25] | √ | …low incidence of lymphoma and lack of temporal relationship points to a strong safety profile thus far in regards to tacrolimus and lymphoma. | |
| Munzenberger 2007 [26] | √ | …no data that show that TCIs are associated with an increased risk of lymphoproliferative disease…lymphoproliferative disease was induced only when doses of TCIs well above the maximum recommended human doses were used. | |
| Orlow 2007 [27] | √ | …no evidence to suggest that there is any increased risk of malignancy associated with TCIs. | |
| Ormerod 2005 [28] | √ | …no evidence to date to suggest an increased risk of cutaneous or visceral cancer. | |
| Ortiz de Frutos 2008 [29] | √ | …with the current information, it cannot be associated to an increase of any type of neoplasmsb. | |
| Patel 2007 [30] | √ | …no established causal link between the topical immunomodulators tacrolimus and pimecrolimus and…malignancy. | |
| Ring 2008 [31] | √ | …the potential risk of malignancy seems to be low. | |
| Rustin 2007 [32] | √ | …no evidence of a causal link between the use of tacrolimus ointment and the rare cases of skin cancer that have been reported. | |
| Sánchez-Pérez 2008 [33] | √ | …there doesn’t exist scientific evidence of increase of skin cancer, lymphomas or systemic immunosuppression in patients that use…topical tacrolimusb. | |
| Spergel 2006 [34] | √ | …studies from clinical trials, systemic absorption, and post-marketing surveillance show no evidence for this systemic immunosuppression or increased risk for any malignancy. …no evidence of increased incidence of lymphoma with short-term or intermittent long-term …tacrolimus and pimecrolimus… |
|
| Tennis 2011 [35] | √ | …the hypothesis that pimecrolimus and tacrolimus cause malignancy…has not been supported by the epidemiological studies to date… | |
| Thaçi 2007 [36] | √ | …current scientific data do not support increased concern for risk of malignancy. | |
| Thaçi 2010 [37] | √ | …no scientific evidence of an increased risk for malignancy due to a topical treatment with calcineurin inhibitors. | |
| Weischer 2007 [38] | √ | …tumor risk of topical immunomodulators is lower than the FDA black box warning may indicate. | |
| Werfel 2009 [39] | √ | …clinical studies with pimecrolimus have not shown any evidence of an increased risk of malignancy…analysis of spontaneously reported adverse events has also not shown any evidence of malignancy… | |
aReview articles or meta-analyses that assess the lymphoma risk of TCIs were identified by querying PubMed with the terms (lymphoma OR neoplasm OR malignancy OR cancer) AND (topical calcineurin inhibitor OR TCI OR pimecrolimus OR tacrolimus) AND (atopic dermatitis OR eczema), and filtering for meta-analysis, review, and systematic review articles. Articles were excluded if lymphoma risk was not the main focus of the article, or if authors did not come to a conclusion regarding lymphoma risk (or merely referenced conclusions from other papers)
bStatement is quoted from the translated abstract of a foreign-language article