Key points from the evidence | External genital and perianal warts: green tea (Camellia sinensis) leaf extract 10% ointment | Advice

Summary

Green tea (Camellia sinensis) leaf extract 10% ointment (Catephen) is a self‑administered topical treatment for external genital and perianal warts. In 2 randomised controlled trials (RCTs) involving a total of 1005 adults, green tea leaf extract 10% ointment was 2‑fold more effective than vehicle (placebo) ointment in terms of complete clearance of all baseline and new warts over a maximum treatment duration of 16 weeks. Most reported adverse events were local skin reactions, and were mild or moderate in severity. There are no published comparisons with other active treatments for genital and perianal warts.

Regulatory status: Catephen 10% ointment was launched in the UK in November 2015.

Effectiveness

In 2 RCTs (n=1005), up to 16 weeks, statistically significantly more people using green tea leaf extract 10% ointment had complete clearance of warts compared with vehicle (53.6% and 35.4% respectively, p<0.001).
Over a 12‑week follow‑up phase, recurrence rates were low (approximately 6%), with no statistically significant difference between the groups. Recurrence rates beyond 12 weeks are not known.

Safety

In the 2 RCTs, local skin reactions were reported by 82.9% of participants using green tea leaf extract 10% ointment and 60.4% using vehicle (no statistical analysis reported).
Severe local reactions were more common in the active treatment group (27.4%) compared with the vehicle group (4.4%), although very few people discontinued treatment due to adverse effects.
The summary of product characteristics states that local reactions at the application site, such as redness, itching and burning, occur in at least 1 in 10 people.
The maximum duration of treatment for the ointment is 16 weeks; the safety profile beyond this time period is not known.

Patient factors

UK national guidelines on the management of anogenital warts state that treatment decisions should be made only after discussing the appropriate options with the person.
There are 3 self‑administered topical treatment options for external genital and perianal warts. All can cause local skin reactions.
The maximum treatment duration for green tea leaf extract ointment is 16 weeks, with application 3 times a day. The maximum duration ranges from 4 to 5 weeks for podophyllotoxin preparations to 16 weeks for imiquimod 5% cream. These treatments require less frequent administration than green tea leaf extract ointment.
These 3 treatments are available in a variety of formulations and may vary in their ease of application.

Resource implications

As well as the unit cost, the cost of treatments for anogenital warts is dependent on the size of the area treated and the duration required.
Green tea leaf extract 10% ointment (Catephen) is available in a 15 g tube, costing £39.00 (MIMS, November 2015).
The maximum cost per treatment course for green tea leaf extract 10% ointment is £234.
Imiquimod 5% cream costs up to £194.40 per treatment course and podophyllotoxin‑based products cost approximately £15 per treatment course.

Introduction and current guidance

Anogenital warts (condylomata acuminata) are benign, proliferative growths caused by human papillomavirus (HPV). They are 1 of the most common conditions treated in genitourinary medicine (sexual health) clinics, with over 130,000 cases treated each year in the UK.

Treatment choice in genital warts is influenced by the number and size of warts, location of warts, gender and degree of skin keratinisation. Treatment options recommended by the British Association for Sexual Health and HIV (BASHH) in their UK national guidelines on the management of anogenital warts include self‑applied treatments (podophyllotoxin 0.5% solution or 0.15% cream, imiquimod 5% cream and green tea leaf extract 10%) and ablative methods (cryotherapy, excision, trichloroacetic acid and electrocautery). No treatment is also an option because approximately one‑third of visible warts disappear spontaneously within 6 months.

Green tea leaf extract 10% ointment is listed in the BASHH guideline but is not included in the treatment algorithms. The guideline notes that the evidence to direct first- and second‑line treatment is not strong and treatments have significant failure and relapse rates.

Full text of introduction and current guidance.

Product overview

Catephen 10% ointment contains Camellia sinensis (green tea) leaf extract. Its mechanism of action is not known (Catephen summary of product characteristics).

Catephen is licensed for the cutaneous treatment of external genital and perianal warts in immunocompetent adults. It is applied 3 times daily until all warts have cleared, or for a maximum duration of 16 weeks.

Catephen is available in a 15 g tube, costing £39.00 (MIMS, November 2015).

Full text of product overview.

Evidence review

This evidence summary is based on 2 randomised controlled trials (RCTs, Stockfleth et al. 2008 and Tatti et al. 2008) that compared green tea leaf extract 10% ointment with vehicle (placebo) for the treatment of external genital and perianal warts in adults for up to 16 weeks. The results of these 2 RCTs have been combined in a meta‑analysis by Tatti et al. (2010). The pooled results are shown below.

In 2 RCTs (total n=1005), green tea leaf extract 10% ointment (n=401) was more effective than vehicle ointment (n=207) for complete clearance of all baseline and newly developed genital and perianal warts (53.6% compared with 35.4% respectively, odds ratio 2.10, 95% confidence interval [CI] 1.49 to 2.98, p<0.001). Similar results were observed for the clearance of baseline warts only (excluding new warts that developed during the treatment period).
Statistically significant differences between green tea leaf extract 10% and vehicle were observed for clearance of all warts at week 6, and for the rest of the 16‑week treatment period.
Participants with complete clearance of all warts during the treatment period entered into a 12‑week follow‑up phase to assess for recurrence. There was no statistically significant difference in recurrence rates for people receiving green tea leaf extract 10% (6.5%) compared with vehicle (5.8%). Recurrence rates beyond 12 weeks are not known.
Treatment‑emergent local skin reactions occurred in 82.9% of people receiving green tea leaf extract 10% and 60.4% of people receiving vehicle (statistical analysis not reported). Local skin reactions were mainly mild or moderate, and their frequency was independent on wart location.
More people in the green tea leaf extract 10% group experienced severe local reactions compared with vehicle (27.4% and 4.4% respectively). Severe local reactions were more common in women than men (34.4% and 21.2% respectively). Few people discontinued treatment due to adverse effects (1.0% green tea extract and 0.5% vehicle).
The maximum incidence of local reactions with active treatment was reached after 4 weeks. Tatti et al. (2010) suggest that local reactions at the application site are part of the mechanism of action for green tea leaf extract and necessary for achieving clinical response.
Very common adverse events (occurring in at least 1 in 10 people) reported in the summary of product characteristics are erythema, pruritus, irritation or burning, pain, ulcer, oedema, induration (hardening of soft tissue) and vesicles.

Full text of evidence review.

Context

Green tea leaf extract 10% ointment is a new self‑administered topical treatment for external genital and perianal warts. Other self‑administered topical treatments available in the UK are podophyllotoxin 0.5% solution, podophyllotoxin 0.15% cream and imiquimod 5% cream.

The cost of topical treatments for genital and perianal warts depends on the unit cost of the medication, the area being treated and the duration of treatment. Based on the maximum dose and assuming the full treatment course is required, green tea leaf extract 10% ointment is the most costly topical treatment for external genital and perianal warts, at £234.00 for 16 weeks' treatment. Imiquimod 5% cream (Aldara) costs £194.40 for a 16 week course, and podophyllotoxin products (Warticon Cream, Warticon Solution and Condyline solution) cost between £14.49 and £17.83 for a 4 to 5 week course (prices from Drug Tariff, November 2015 or MIMS, November 2015).

Full text of context.

Estimated impact for the NHS

Prescribers and local decision makers need to consider the available evidence on efficacy and safety, as well as cost and individual patient factors, when making decisions about using green tea leaf extract 10% ointment or another topical treatment for external genital warts. There are no RCTs comparing green tea leaf extract 10% ointment with other active treatments for external genital and perianal warts, and topical treatments have significant failure and relapse rates.

Full text of estimated impact for the NHS.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.