Review question
In this Cochrane Review we assessed the effectiveness and safety of imiquimod compared to placebo and any other patient-applied or provider-administered therapy for treatment of anogenital warts (AGW) in adults without impaired immune responsiveness
Background
Although 30% of AGW spontaneously vanish without treatment, currently there is no way to know whether a lesion will go or remain. There are a wide range of treatment options and the choice is based on the experience of the clinicians, patient preferences and adverse effects.
Trial characteristics
We searched the available literature up to 15 April 2014 and included 10 trials with 1734 participants. The trials included both men and women aged over 18 years with a clinical diagnosis of AGW. Eight trials included people that had been treated before for AGW and two trials included people that had not needed to be treated before for AGW. In most trials, people used 5% imiquimod three times per week and trial length ranged from eight weeks to 12 weeks. However, several included trials compared different concentrations and frequencies. Six trials compared imiquimod versus placebo (1294 participants) and two trials compared imiquimod with patient-applied treatment (105 participants) or with another provider-administered treatment (335 participants). Six out of ten included trials were funded by industry.
Key results
Compared with placebo, imiquimod was superior to achieve complete and partial regression but not in the rate of recurrence, appearance of new warts or the frequency of systemic reactions. The patients allocated to imiquimod treatment had a higher frequency of pain and local adverse reactions. When imiquimod was compared with any other patient-applied treatment, we were unable to determine whether it led to differences in the rate of complete or partial regression, recurrence or the presence of local reactions, although systemic adverse reactions were lower in the imiquimod group. Finally, when imiquimod use was compared with any other provider-administered treatment it was unclear whether there were differences in terms of complete regression. Imiquimod was associated with a lower rate of recurrence during the first six months after treatment and with less pain or local reactions.
Quality of evidence
The quality of evidence was very low for the outcomes reported in this systematic review due to some limitations on risk of bias, imprecision and inconsistency in the included trials. We have very little confidence in the effect estimate.
The benefits and harms of imiquimod compared with placebo should be regarded with caution due to the risk of bias, imprecision and inconsistency for many of the outcomes we assessed in this Cochrane Review. The evidence for many of the outcomes that show imiquimod and patient-applied treatment (podophyllotoxin or podophyllin) confer similar benefits but fewer systematic reactions with the Imiquimod, is of low or very low quality. The quality of evidence for the outcomes assessing imiquimod and other provider-administered treatment were of very low quality.
30% of people with anogenital warts (AGW) have spontaneous regression of lesions but there is no way to determine whether a specific lesion will remain. There are a wide range of options available for treating people with AGW and selection is based on clinician's experience, patient preferences and adverse effects. The imiquimod could offer the advantages of patient-applied therapies without incurring the limitations of provider-administered treatments.
To assess the effectiveness and safety of imiquimod for the treatment of AGW in non-immunocompromised adults.
We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (15 April 2014), CENTRAL (1991 to 15 April 2014), MEDLINE (1946 to 15 April 2014), EMBASE (1947 to 15 April 2014), LILACS (1982 to 15 April 2014), World Health Organization International Clinical Trials Registry (ICTRP) (15 April 2014), ClinicalTrials.gov (15 April 2014), Web of Science (2001 to 15 April 2014) and OpenGrey (15 April 2014). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies.
Randomized controlled trials (RCTs) comparing the use of imiquimod with placebo, any other patient-applied or any other provider-administered treatment (excluding interferon and 5-fluorouracil which are assessed in other Cochrane Reviews) for the treatment of AGW in non-immunocompromised adults.
Three review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. We resolved any disagreements through consensus. The quality of the evidence was assessed using the GRADE approach.
Ten RCTs (1734 participants) met our inclusion criteria of which six were funded by industry. We judged the risk of bias of the included trials as high. Six trials (1294 participants) compared the use of imiquimod versus placebo. There was very low quality evidence that imiquimod was superior to placebo in achieving complete and partial regression (RR 4.03, 95% CI 2.03 to 7.99; RR 2.56, 95% CI 2.05 to 3.20, respectively). When compared with placebo, the effects of imiquimod on recurrence (RR 2.76, 95% CI 0.70 to 10.91), appearance of new warts (RR 0.76, 95% CI 0.58 to 1.00) and frequency of systemic adverse reactions (RR 0.91, 95% CI 0.63 to 1.32) were imprecise. We downgraded the quality of evidence to low or very low. There was low quality evidence that imiquimod led to more local adverse reactions (RR 1.73, 95% CI 1.18 to 2.53) and pain (RR 11.84, 95% CI 3.36 to 41.63).
Two trials (105 participants) compared the use of imiquimod versus any other patient-applied treatment (podophyllotoxin and podophyllin). The estimated effects of imiquimod on complete regression (RR 1.09, 95% CI 0.80 to 1.48), partial regression (RR 0.77, 95% CI 0.40 to 1.47), recurrence (RR 0.49, 95% CI 0.21 to 1.11) or the presence of local adverse reactions (RR 1.24, 95% CI 1.00 to 1.54) were imprecise (very low quality evidence). There was low quality evidence that systemic adverse reactions were less frequent with imiquimod (RR 0.30, 95% CI 0.09 to 0.98).
Finally, two trials (335 participants) compared imiquimod with any other provider-administered treatment (ablative methods and cryotherapy). There was very low quality of evidence that imiquimod did not have a lower frequency of complete regression (RR 0.84, 95% CI 0.56 to 1.28). There was very low quality evidence that imiquimod led to a lower rate of recurrence during six-month follow-up (RR 0.24, 95% CI 0.10 to 0.56) but this did not translate in to a lower recurrence from six to 12 months (RR 0.71, 95% CI 0.40 to 1.25; very low quality evidence). There was very low quality evidence that imiquimod was associated with less pain (RR 0.30, 95% CI 0.17 to 0.54) and fewer local reactions (RR 0.55, 95% CI 0.40 to 0.74).