Difficult-to-treat scabies: oral ivermectin

Evidence strengths and limitations

A Cochrane systematic review has evaluated topical and systemic drugs for treating scabies. The review included 1 randomised controlled trial (RCT) that compared oral ivermectin with placebo, 5 RCTs that compared oral ivermectin with benzyl benzoate and 2 RCTs that compared oral ivermectin with permethrin. Since the publication of the Cochrane systematic review, 4 RCTs comparing the efficacy of oral ivermectin with permethrin have been published. All of these trials assessed ivermectin for the treatment of classical or uncomplicated scabies.

The RCTs included different treatment regimens and varying lengths of follow-up, which may explain some of the heterogeneity in the results of the different studies.

Three trials (Macotela-Ruíz and Peña-González 1993, Bachewar et al. 2009 and Chhaiya et al. 2012) assessed treatment failure after just 1 week of follow-up, which is not enough time to have confidence in the outcome. The European summary of product characteristics for Stromectol 3 mg tablets (Merck Sharp & Dohme: personal communication December 2013), states that, for classical scabies, recovery is considered definite only after 4 weeks have elapsed since treatment. Persistence of pruritus or scraping lesions does not justify a second treatment before this date. Administration of a second dose within 2 weeks after the initial dose should only be considered when new specific lesions occur or when parasitological examination is positive.

The authors of the Cochrane systematic review suggested that ivermectin may be slower in achieving cure than topical benzyl benzoate, and this may also be the case compared with permethrin.

The European summary of product characteristics for Stromectol 3 mg tablets (Merck Sharp & Dohme: personal communication December 2013) also states that the recommended dose for scabies is a single oral dose of ivermectin 200 micrograms/kg body weight. Most of the trials used this dose, but Glaziou et al. (1993) and Ly et al. (2009) used lower doses of 100 micrograms/kg and 150–200 micrograms/kg respectively.

The quality of relevant individual studies included in the Cochrane systematic review is summarised in table 8. The Cochrane review concluded that only 1 trial with ivermectin described both adequate randomisation sequence generation and adequate allocation concealment, and the majority of the reports described neither adequately. Blinding was absent or unclear in many of the trials. The same limitations can be applied to the 4 RCTs published since the Cochrane review. Most of the RCTs were conducted in countries with few healthcare resources, such as India, and it is unclear how applicable the findings will be to people in the UK with scabies. Most were also small trials (50–200 participants), which are too small to properly assess serious but rare potential adverse effects.

Table 8 Quality of trials included in the Cochrane systematic review

The quality of the 4 additional RCTs is described briefly below.

Chhaiya et al. (2012) was an open-label (unblinded) RCT. Randomisation was adequate and the method of allocation described suggests that this was concealed.

Goldust et al. (2012) was a single-blind (to the assessor) RCT. The randomisation procedure was not reported and it is unclear if allocation was concealed.

Saqib et al. (2012) states that it was a quasi-experimental study, but then goes on to state that participants were randomly divided into 2 groups. The randomisation procedure was not reported and it is unclear if allocation was concealed. The study was open-label (unblinded).

Sharma and Singal (2011) was a double-blind RCT that used both placebo topical applications and tablets. Randomisation was adequate and the method of allocation described suggests that this was concealed.

No RCTs of oral ivermectin for the treatment of crusted scabies were identified.

The results of uncontrolled trials and case series with 4 or more participants with crusted scabies that reported cure rates or treatment failures are included in this evidence summary. Multiple doses of oral ivermectin and/or ivermectin in combination with topical therapy were frequently administered in these small studies. The results of these studies should be interpreted with caution because of the potential for publication bias (publication of cases with good outcomes).