Six RCTs were included. However, data from one study that included only patients with human immunodeficiency virus (HIV) infection were not pooled with data from the other five studies.
Quality assessment: 4 studies scored three on the quality scale and 2 studies scored four.
Complete clearance of warts (5 RCTs, n=588): 51% of patients (95% CI: 45, 56) reported complete wart clearance with the highest concentration of imiquimod, compared with 6% (95% CI: 3, 8) of those in the placebo group (relative benefit 8.3, 95% CI: 5.2, 13). The NNT was 2.2 (95% CI: 2.0, 2.6). Fewer patients achieved complete wart clearance with 1% imiquimod in 2 RCTs (n=387; relative benefit 2.4, 95% CI: 1.4, 4.4). Imiquimod 5% cream was significantly more effective than imiquimod 1% cream (z=6.5, P<0.001). The results were more favourable for women than men (z=4.2, P<0.001).
At least 50% reduction in wart area (4 RCTs, n=528): this outcome was reported in 72% (95% CI: 67, 78) of the patients treated with imiquimod 5% cream, compared with 20% (95% CI: 15, 25) of those treated with placebo (relative benefit 3.6, 95% CI: 2.8, 4.6). The NNT was 1.9 (95% CI: 1.7, 2.2). Imiquimod 5% cream was significantly more effective than imiquimod 1% cream for this outcome (z=7.1, P<0.001).
Warts completely cured without recurrence (3 RCTs, n=507): warts did not recur in 37% (95% CI: 31, 43) of the patients treated with imiquimod 5% cream, compared with 4% (95% CI: 2, 6) of those treated with placebo (relative benefit 9.0, 95% CI: 4.9, 17). The NNT was 3.0 (95% CI: 2.5, 3.8). Imiquimod 5% cream was significantly more effective than imiquimod 1% cream (z=5.2, P<0.001).
New warts (3 RCTs, n not reported): new warts appeared in 30% (95% CI: 24, 36) of the patients treated with imiquimod 5%, in 48% (95% CI: 41, 55) of those treated with imiquimod 1%, and in 48% (95% CI: 42, 55) of those treated with placebo. The proportion of new warts that had completely cleared by the end of the study (2 RCTs, n=119) was 39% (95% CI: 24, 54) in patients treated with imiquimod 5%, compared with 21% (95% CI: 12, 30) in those treated with placebo (relative benefit 2.0, 95% CI: 1.1, 3.7). The NNT was 5.4 (95% CI: 2.8, 91).
Recurrence (3 RCTs, n not reported): in 3 large trials, 22% of the patients treated with imiquimod 5% had a recurrence or reinfection of warts.
The authors reported that the use of a random-effects model made no difference to the interpretation of the results.
Adverse events: commonly reported adverse events were localised itching, erythema, burning and erosion or excoriation. There was no difference between the placebo and imiquimod groups in terms of the number of patients withdrawing from treatment due to adverse events(relative risk 1.7, 95% CI: 0.4, 99). More patients in the placebo group withdrew due to a lack of treatment effect (7.4%; 95% CI: 4.3, 11) than in the imiquimod group (1.7%; 95% CI: 0.3, 3.1) (relative risk 0.3, 95% CI: 0.1, 0.7).
HIV-infected patients (1 RCT, n=100): imiquimod showed little benefit in terms of warts completely cleared. The wart area was reduced by at least 50% in 38% of the patients treated with imiquimod, compared with 14% of those receiving placebo.