01 JULY 2009 ISSUE
Imiquimod use in genital warts
Nicky Perkins
The availability of Aldara (imiquimod) on Special Authority has revolutionised the treatment of genital warts. No longer do we have to agonise over how much it will cost a patient to use, nor do we have to look at ways to reduce the cost by using less than a full sachet per application, or encouraging patients to buy individual sachets at a time to reduce unnecessary expense. At last we have a useful self-applied treatment for women and a way to avoid the pain and inconvenience of repeated visits to the clinic for cryotherapy.
Imiquimod has good data supporting its use, is a patient-applied treatment, thus avoiding unnecessary clinic visits, and is easy to apply. However, there are potential issues with its use: it is not licensed for use in pregnancy; it can have unpleasant systemic side effects; it is not ideal for treating all types of genital warts; and it can, on occasion, cause severe genital ulceration and pain. What follows is a brief review of imiquimod and practical advice on its use in the treatment of genital warts.
Imiquimod is an imidazoquinoline, an immune response modifier that induces production of interferon and other cytokines, including TNF and interleukins. The immunological activity is consistent with a TH1 cell-mediated response and this local response to application of imiquimod induces clearance of genital warts. This mechanism of action is completely different from other treatment options for genital warts which rely on direct tissue destruction.
A number of double-blind placebo-controlled trials have demonstrated the efficacy of imiquimod. Response appears to be better in women than men, probably due to less keratinised skin on the vulva. The initial response rate is similar to other modes of treatment; however, there are some data supporting a reduced recurrence rate following treatment with imiquimod.
Who should use imiquimod?
Ministry of Health Special Authority application states imiquimod will be funded for use where:
• the patient has external anogenital warts and podophyllotoxin has been tried and failed (or is contraindicated) OR
• the patient has external anogenital warts and podophyllotoxin is unable to be applied accurately to the site.
Importantly, these criteria allow imiquimod to be used appropriately for:
• women, who in general are unable to apply podophyllotoxin (Condyline) accurately to vulval warts
• men and women with perianal warts, since it is not possible to apply podophyllotoxin accurately to this area.
What kinds of warts are appropriate for imiquimod treatment?
Imiquimod may be used for treatment of any kind of genital warts. However, since clinical response relies on local epithelial absorption, warts in moist areas with less keratinised epithelium tend to respond better, eg, subpreputial, introital and perianal warts. In addition, if a patient only has a small number of genital warts, it may be quicker and easier to treat these with cryotherapy.
When should imiquimod not be used?
Imiquimod should not be used for treatment of vaginal, cervical, rectal or intra-anal warts, as it has not been evaluated for use in these sites. Imiquimod is also not licensed for use in pregnancy, and specialist oversight is required for treatment of patients with autoimmune conditions or who are immunocompromised. The panel gives hints on use of imiquimod.
What about side effects?
Side effects are common with imiquimod use but are, in general, manageable, as less than 2 per cent of patients discontinue treatment because of them. The most common side effect is skin irritation and erythema, which usually occurs between weeks two and six of treatment. This reaction is considered to be part of the immune response and usually indicates the treatment is working. Lack of any local irritation or erythema is associated with lack of response to treatment.
Occasionally, irritation may be severe and results in significant pain and genital ulceration. This ulceration may look very similar to that seen with genital herpes, and in this situation it is important to exclude genital herpes as a concurrent diagnosis. If local side effects are significant, there are two methods of dealing with this:
• stop applications until the skin has healed and then try cautious reintroduction
• reduce applications to once or twice weekly and then increase again, if tolerated, to three times weekly.
In general, healing is complete and scarring is absent. Systemic symptoms are very uncommon and systemic absorption is <1 per cent, but flu-like symptoms may infrequently occur.
Can imiquimod be used with other treatments?
An advantage with imiquimod treatment is it can be applied by the patient at home. However, with some patients where progress is slow, imiquimod can be used as part of a combined treatment regimen with cryotherapy (or sometimes laser or hyfrecation). In this situation, the patient uses imiquimod at home and is seen weekly or fortnightly for selected cryotherapy to some areas. This approach can be successful, but it is very important care is taken not to over-traumatise the genital skin. In general, I ask patients to take a break from imiquimod for a few days after cryotherapy and to only apply it if they feel their skin is comfortable.
What level of monitoring is needed?
Although imiquimod is self-applied at home, it is essential treatment is monitored. I have met a number of patients who have been sent away with imiquimod sachets, given inadequate instructions about use, and then not followed up. This may result in, at best, non-response to treatment and, at worst, severe genital ulceration and pain. Patients should be counselled about side effects and advised if irritation is severe they should stop treatment and attend for review.
If all is going well, patients should be reviewed at the least every four weeks, so progress can be monitored and other treatment instituted if progress is unsatisfactory. Follow-up visits also provide a valuable opportunity for ongoing counselling, STI screening and contraceptive advice.
Nicky Perkins is lead clinician at Auckland Sexual Health Service
Imiquimod treatment: practical hints
• More is not better: imiquimod should only be used as directed, three times weekly for a maximum of 16 weeks. More frequent application does not improve efficacy and increases the chance of the patient experiencing significant side effects.
• Although the manufacturer recommends using an entire sachet per application, if the patient has a small surface area affected, then one sachet may be enough for several applications. The sachet may be pierced with a pin and a small amount used for an application. Once opened, the sachet should be wrapped in gladwrap and placed in the fridge, as exposure to the air causes rapid degradation of the product.
• Imiquimod is designed to be applied to the site. Thus, it is not necessary to apply cream only to the individual genital warts (compare use of podophyllotoxin). Since its mode of action is by immune enhancement, imiquimod may be applied to the general area affected by genital warts.
• Imiquimod cream should be applied at night, and washed off in the morning to allow maximum undisturbed time for absorption.
• Patients should not have sex following an application of imiquimod as the cream may rub off onto the skin of a sexual partner, and may weaken latex condoms.
Key points
• Imiquimod (Aldara) is a very useful addition to available
treatment options for genital warts.
• As imiquimod is now available on Special Authority it means many more patients are able to benefit from its use.
• Particular advantages are that patients can apply the treatment themselves, and it is applied to the affected site, thus accurate application to individual lesions is not necessary.
• Imiquimod is not an appropriate treatment for all situations, and, like any other therapy, it has potential side effects.
• It is the clinician’s responsibility to counsel patients fully about appropriate use and ensure adequate follow-up, in order to maximise benefit obtained.
« Go Back