Background Interferons are natural messenger proteins that are used to treat various disease entities. Due to their immunomodulating, antiviral and antiproliferative effects, the systemic administration of interferons after ablative treatment for anogenital warts (AGWs) has been advocated to increase clearance and decrease recurrence rates. However, studies investigating the efficacy of adjuvant systemic interferon have yielded inconsistent results. The objective of this systematic review and meta-analysis was to comprehensively assess and evaluate the available evidence from randomised controlled trials.
Methods A literature search was conducted in Cochrane Central Register of Controlled Trials, Embase and MEDLINE. Available data were classified according to the interferon type and dosage. Pooled effect estimates were calculated for predefined outcomes. The Cochrane Collaboration’s risk of bias tool was used to assess the included trials and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate our confidence in the effect estimates.
Results Twelve trials were identified that met the inclusion criteria and assessed immunocompetent patients with external AGW. Compared with placebo, adjuvant alpha-, beta- and gamma-interferon were generally not significantly superior in terms of complete clearance over the short, intermediate or long term, nor with regard to intermediate- or long-term recurrence. However, the low-dose subgroup of adjuvant alpha-interferon was significantly superior compared with placebo regarding intermediate-term complete clearance and recurrence. Further data were available for the comparison of different dosages of alpha- and beta-interferon and for comparisons of the three interferon types. No significant differences were seen in these comparisons regarding efficacy. Data on quality of life were not available.
Conclusions The GRADE quality of the evidence ranged from ‘very low’ to ‘high’. The significantly higher efficacy of low-dose alpha-interferon compared with placebo was based on a single trial, and our confidence in the effect estimates rated as ‘low’. Overall, we found no reliable evidence favouring the systemic use of interferon after ablative treatment of AGW.
- human papilloma virus
- condylomata acuminata
- systematic reviews
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Contributors LW, RNW, CD and AN developed the research question and methods section. LW developed the search strategy and excluded doublets. LW and RNW selected eligible studies during the title/abstract screening and full-text evaluation, extracted data from the included studies, appraised the quality of the evidence, entered and double-checked data for RevMan and analysed/interpreted the data. AN and CD were involved in cases of dissent with respect to extracted data/evaluations and participated in analysing and interpreting the data. RNW, AN, CD and MG contributed to the final editing of the draft. LW developed the draft of the manuscript, coordinated contributions of the coauthors and compiled the final draft.
Competing interests The Division of Evidence Based Medicine (dEBM) received research grants from various entities. The conduct of the current review was not funded. Previously, the conduct of a systematic review and meta-analysis of topical interventions for anogenital warts in immunocompetent patients has been funded with an institutional research grant by Meda Pharma. The dEBM received research grants not associated with the current work by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V., European Academy of Dermatology and Venereology, Medigene, European Dermatology Forum, Pfizer, Merz, Deutsche Dermatologische Gesellschaft, Deutsche Gesellschaft für Allergologie und klinische Immunologie, Deutsche Dermatologische Akademie and GSK. The dEBM is currently involved in the development of a German clinical practice guideline on the management of human papillomavirus-associated anogenital lesions. AN is responsible for the grants given to dEBM. LW, RNW, CD and MG declare to have no further conflicts of interests. AN has received personal honoraria for educational activity with direct or indirect sponsoring from Novartis, Pfizer, Boehringer Ingelheim, Bayer Healthcare, Jansen and Meda.
Patient consent This was a systematic review and meta-analysis.
Provenance and peer review Not commissioned; externally peer reviewed.
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