Importance: Topical calcineurin inhibitors (TCIs), including tacrolimus and pimecrolimus, have been widely used for the treatment of vitiligo; however, the efficacy of TCI monotherapy is often underestimated.
Objectives: To estimate the treatment responses to both TCI monotherapy and TCI accompanied by phototherapy for vitiligo, based on relevant prospective studies, and to systematically review the mechanism of action of TCIs for vitiligo treatment.
Data sources: A comprehensive search of the MEDLINE, Embase, Web of Science and Cochrane Library databases from the date of database inception to August 6, 2018, was conducted. The main key words used were vitiligo, topical calcineurin inhibitor, tacrolimus, pimecrolimus, and FK506.
Study selection: Of 250 studies initially identified, the full texts of 102 articles were assessed for eligibility. A total of 56 studies were identified: 11 studies on the TCI mechanism, 36 studies on TCI monotherapy, 12 studies on TCI plus phototherapy, and 1 study on TCI maintenance therapy.
Data extraction and synthesis: Two reviewers independently extracted data on study design, patients, intervention characteristics, and outcomes. Random-effects meta-analyses using the generic inverse variance weighting were performed for the TCI monotherapy and TCI plus phototherapy groups.
Main outcomes and measures: The primary outcomes were the rates of at least mild (≥25%), at least moderate (≥50%), and marked (≥75%) repigmentation responses to treatment. These rates were calculated by dividing the number of participants in an individual study who showed the corresponding repigmentation by the total number of participants who completed that study.
Results: In the 56 studies included in the analysis, 46 (1499 patients) were selected to evaluate treatment response. For TCI monotherapy, an at least mild response was achieved in 55.0% (95% CI, 42.2%-67.8%) of 560 patients in 21 studies, an at least moderate response in 38.5% (95% CI, 28.2%-48.8%) of 619 patients in 23 studies, and a marked response in 18.1% (95% CI, 13.2%-23.1%) of 520 patients in 19 studies after median treatment duration of 3 months (range, 2-7 months). In the subgroup analyses, face and neck lesions showed an at least mild response in 73.1% (95% CI, 32.6-83.5%) of patients, and a marked response in 35.4% (95% CI, 24.9-46.0%) of patients. For TCI plus phototherapy, an at least mild response to TCI plus phototherapy was achieved in 89.5% (95% CI, 81.1-97.9%) of patients, and a marked response was achieved in 47.5% (95% CI, 30.6-64.4%) of patients.
Conclusions and relevance: The use of TCIs, both as a monotherapy and in combination with phototherapy, should be encouraged in patients with vitiligo.