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Actinic keratosis update: imiquimod and fluorouracil

Imiquimod
Fluorouracil
Comment

Bandolier 143 examined a systematic review of 3% diclofenac gels for treating actinic keratosis. At the time we commented that there are few systematic reviews, but now like buses, several have come along together. Two [1,2] have looked at imiquimod, and two [2,3] fluorouracil, and we can compare these with the evidence available for topical diclofenac.


Imiquimod

One of the reviews [1] has the most detailed descriptions of studies and most trials. It used a thorough literature search using a number of databases and strategies (to August 2005) for randomised trials, and abstracted pre-defined outcomes of efficacy and harm.

It found five randomised placebo (vehicle) comparisons with 1,293 patients, with trial duration of 12-16 weeks. Quality of the trials was high, and they all used one sachet of 5% imiquimod cream applied to lesions on face and balding scalp twice or three times a week.

Complete and partial (>75%) clearance occurred more frequently with imiquimod (Table 1), with numbers needed to treat for complete and partial clearance of 2.2 and 1.8 respectively (Table 1). The three trials that described a formalised lesion count, possibly reflecting higher quality studies, had even lower (better) NNTs of 1.9 and 1.5 for complete and partial clearance.



Table 1: Summary of efficacy studies of topical imiquimod, 5-fluorouracil, and diclofenac on complete and partial clearance of lesions after end of therapy



Number of
Percent with outcome
Treatment/outcome
Trials
Patients
Active
Placebo
NNT
(95%CI)
Imiquimod - complete clearance
5
1293
50
5
2.2 (2.0 to 2.5)
Imiquimod - >75% clearance
5
1293
65
11
1.8 (1.7 to 2.0)
Fluorouracil - complete clearance
6
145
52
Diclofenac - complete clearance
2
214
42
16
3.7 (2.6 to 3.6)
Diclofenac - complete clearance including new lesions
3
364
39
12
3.8 (2.8 to 5.5)


Local adverse events were more common with imiquimod than vehicle, occurring in 43% of patients. These were mainly erythema (27%), scabbing (21%), flaking (9%), erosion (6%), oedema (4%), and weeping (3%). There were no serious adverse events, and adverse event withdrawals were no more frequent with imiquimod than placebo.


Fluorouracil

The best data comes from a review [2] that was not overtly systematic, but which for fluorouracil contained more trials and patients than a later systematic review [3]. The results in Table 1 relate the efficacy of 0.5% 5-fl;uorouracil in randomised, double blind trials with the outcome of complete clearance after four weeks of therapy. One study found lower rates of clearance with shorter use. This useful review [2] also comments on photodynamic therapy and combination treatments.


Comment

The information we have for all three of the treatments is summarised in Table 1. Clearly, the amount and quality of information available for imiquimod dwarfs that from diclofenac and fluorouracil. For fluorouracil, the worry is that even the little information available comes from studies that would have been excluded from any systematic review using formal quality constraints for included studies.

The imiquimod review also examined adverse events in great detail, and again that gives confidence that information about therapy provided for patients is relevant and useful.

What we have is the usual conundrum of new treatments with good trials well done, and older therapies with little useful information from trials, but backed with experience, and some expectation of some efficacy because of that.

References:

  1. G Hadley et al. Imiquimod for actinic keratosis: systematic review and meta-analysis. Journal of Investigative Dermatology 2006. Epub ahead of print. DOI:10.1038/sj.jid.5700264.
  2. JL Jorizzor. Current and novel treatment options for actinic keratosis. Journal of Cutaneous Medicine and Surgery 2005 8(Suppl 3):13-21.
  3. AK Gupta et al. Evaluation of the effectiveness of imiquimod and 5-fluorouracil for the treatment of actinic keratosis: critical review and meta-analysis of efficacy studies. Journal of Cutaneous Medicine and Surgery 2006. Epub ahead of publication.

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