Lancet Infectious Diseases The Lancet Infectious Diseases, Volume 14, Issue 5, Pages 372 - 373, May 2014,

doi:10.1016/S1473-3099(14)70728-5

Imiquimod is not an effective drug for molluscum contagiosum

Kenneth A Katz a In a Review of treatment options for molluscum contagiosum infection, Xiaoying Chen and colleagues1 include imiquimod, citing three small randomised controlled trials and observational data as evidence of its effectiveness. They do not note that findings from two large, well designed, randomised trials (1494-IMIQ and 1495-IMIQ), completed in 2006 but to date unpublished, definitively showed that imiquimod does not effectively treat molluscum contagiosum in children. The two trials together enrolled 702 participants aged 212 years, of whom 470 were randomly assigned to imiquimod 5% cream. At week 18, imiquimod was no more effective than was vehicle-containing cream in clearing molluscum contagiosum (24% vs 26% in one study, 24% vs 28% in the other).2 In 2007, the prescribing information approved by the US Food and Drug Administration (FDA) for imiquimod was updated to incorporate results from these two trials as well as a companion pharmacokinetic study (1490-IMIQ), including a statement that the studies failed to demonstrate efficacy, and new safety concerns.2 That Chen and colleagues do not include these data highlights persistent deficiencies in dissemination of data from randomised controlled trials. These deficiencies are especially glaring in this case, because US taxpayers effectively subsidised the two trials. Acting under authority granted by the Best Pharmaceuticals for Children Act (BPCA), passed by the US Congress to address important gaps in knowledge about the effects of drugs in paediatric populations, the FDA specifically requested data from both trials (and the pharmacokinetic study) from 3M, then the drug's manufacturer. 3 In return, the FDA rewarded 3M with an additional 6 months of marketing exclusivity for imiquimod.3 Unfortunately, the BPCA does not require publication of study results. The two trialslike many BPCA studies4have not been published in medical journals. The public availability of the trial data in the prescribing information and on the FDA website has not translated to awareness in the medical community. Physicians, including those who write review articles, do not routinely search those sources. Indeed, until a colleague and I raised this issue in a recent article, no major review articles, textbook chapters, or online references included these trial findings.3 Even a 2009 systematic review by the Cochrane collaboration failed to capture the trial results in its search.5 As I and others have argued,3, 4 the US Congress should amend the BPCA to require publication of study findings. Physicians, including authors of reviews, should routinely search drug prescribing information and the FDA website for relevant information. The investigators who did the two trials of imiquimod

and molluscum should publish the results showing lack of efficacy. Most importantly, physicians should stop recommending and prescribing imiquimod to treat molluscum contagiosum in children. I am a shareholder in Synta Pharmaceuticals Corp and Arrowhead Research Co. The views presented in this Correspondence are those of the author and do not necessarily represent the views of The Permanente Medical Group.

References
1 Chen X, Anstey AV, Bugert JJ. Molluscum contagiosum virus infection. Lancet Infect Dis 2013; 13: 877-888. Summary | Full Text| PDF(2894KB) | PubMed 2 DailyMed. Aldara (imiquimod) cream for topical use. Revised 4/2007. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7fccca4e-fb8f-42b8-95558f78a5804ed3. (accessed April 1, 2014). 3 Katz KA, Swetman GL. Imiquimod, molluscum, and the need for a better Best Pharmaceuticals for Children. Pediatrics 2013;132: 1-3. PubMed 4 Benjamin DK, Smith PB, Murphy MD, et al. Peer-reviewed publication of clinical trials completed for pediatric exclusivity. JAMA2006; 296: 1266-1273. PubMed 5 van der Wouden JC, van der Sande R, van Suijlekom-Smit LW, et al. Interventions for cutaneous molluscum contagiosum.Cochrane Database Syst Rev 2009; 4. CD004767

a Department of Dermatology, The Permanente Medical Group, Pleasanton, CA 94588, USA