RESEARCH CORNER

Focus on treatment developments in three less commonly researched chronic skin diseases

Kathy Radley, Senior Lecturer, School of Kathy Radley Life and Medical Sciences, University of Background Hertfordshire, and Project Coordinator, Eczema Education Programme, Guy’s and This quarter’s Research Corner takes a focus on chronic skin disease. In dermatology, St Thomas’ NHS Foundation Trust, reviews when considering the term chronic skin disease, it is often the ‘big three’ that spring recent studies on hidradenitis suppurativa, to mind — eczema, acne and psoriasis. The three studies chosen avoid the ‘big three’ rosacea and vitiligo. and focus on chronic skin diseases which, although common, attract less funding and research: hidradenitis suppurativa (HS), rosacea and vitiligo. HS affects 1% of the European population1, rosacea 1-22%2 and vitiligo 1% worldwide3. These papers all have a valuable role in providing evidence base for the management of these conditions.

pain, hidradenitis severity score and duration outcomes graded above low quality of evidence. of remission. 12 RCT studies including 615 Subcutaneous injections with S. aureus lysis participants were included in the review. showed improvement in outcomes graded moderate quality, although this is an old study6 and Key fi ndings has not been repeated since. Many of the 12 studies reviewed had First study methodological fl aws leading to the quality of the Commentary evidence being downgraded. Only 4 trials reported This systematic review has not identifi ed any Citation on outcome of QoL, all reported on adverse trials where the improvement in outcomes led Ingram JR, Woo PN, Chua SL, et al. Interventions effects. Please refer to the systematic review for the to high-quality evidence. The strongest evidence for hidradenitis suppurativa (Review). details of the trials, as the report below is a brief came from the trial indicating the use of weekly Cochrane Database Sys Rev, 2015, Issue 10. summary. The web link to the full review is included dosed adalimumab (double the dose licensed Available at: http://onlinelibrary.wiley.com/ in the citation above and will also give access to the for psoriasis). There is no evidence for the use doi/10.1002/14651858.CD010081.pub2/abstract Cochrane database of systematic reviews. of many oral systemic agents currently used to treat patients with HS. Validity and clinical Context In the pharmacological studies, the trials of meaningfulness of the outcome measures for Hidradenitis suppurativa (HS) is a chronic, anti-TNFα infl iximab dosed at 5mg per kg and HS leads to a lack of clinical trials of a quality for infl ammatory skin condition characterised by adalimumab dosed weekly showed improvements in inclusion in a review such as this. recurrent, painful boils in fl exural sites4. outcomes and rated as moderate quality evidence. Implications The objective of this systematic review is to assess Topical 1% clindamycin solution showed Five ongoing trials considering the effi cacy of the effects of interventions for HS in people of all improvement in outcomes with evidence also biologics in HS have been identifi ed from trial ages. The HS Priority Sharing Partnership in 20135 rated as moderate. Oral ethinyloestradiol and registers but currently there remains little robust identifi ed a gap in evidence for treatment of HS and cyproterone acetate and ethinyloestradiol and evidence for the treatment of HS. this review is a starting point to address these gaps. norgestrel both identifi ed improvements with the evidence-rated moderate. Second study Methods The systematic review included randomised One study reported an improvement in the Citation controlled trials (RCTs) of interventions for HS. patient-reported global assessment looking at Taieb A, Ortonne JP, Ruzicka T, et al. Superiority RCTs were included for any intervention and the oral tetracycline but the evidence is graded low. of ivermectin 1% cream over metronidazole participants required a clinical diagnosis of HS In surgical interventions the use of gentamycin 0.75% cream in treating infl ammatory lesions of made by a medical practitioner. Interventions were sponges versus primary closure alone showed rosacea: a randomised, investigator-blinded trial. Br J grouped into three categories; pharmacological, improvements with the evidence graded as Dermatol 2015, 172: 1103-1110 surgical and other interventions. Primary moderate quality. outcomes measured were quality of life (QoL) Context and adverse effects, with secondary outcomes In the other interventions group, no laser or Rosacea is a relatively common chronic being global assessment by patients and physician, light intervention identifi ed any improvement in infl ammatory skin disease affecting mainly adults,

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predominantly women. There are few treatments validity and reliability of the results. to use, with just 7% saying it was diffi cult and none Focus on treatment developments with a good evidence base. Ivermectin is a Topical ivermectin is licenced in the UK as saying very diffi cult. macrocyclic derivative — an anti-parasitic with Soolantra® cream8. anti-infl ammatory properties. This study sought to Commentary in three less commonly researched compare the effi cacy of ivermectin 1% cream once Implications In the absence of an easy-to-use and valid tool daily with metronidazole 0.75% cream twice daily. This study identifi es an evidence-based treatment this study indicates the VNS has good construct option to discuss with patients. Phase 2 validity (the degree to which scores of a given chronic skin diseases Methods (continuing 36-week trial to look at recurrence) of measurement instrument are consistent with This was an investigator-blind, randomised, parallel the study is reported by Taieb et al9. hypotheses), is acceptable to patients to use and group study. It was conducted over a 16-week identifi es good interpretability. Patients were period, which this paper reports on, with a Third study central to the development of the VNS so this further 36-week period following to investigate is not surprising. Additionally the VNS dealt recurrence. Participants over 18 years of age were Citation with issues of hyperpigmentation, which the % recruited by 64 centres in 10 European countries Batchelor JM, Tan W, Tour S, Yong A, Montgomery repigmentation scale does not. The participants with moderate or severe papulopustular rosacea. AA, Thomas KS. Validation of the vitiligo were self-selecting so may not be totally noticeability scale; a patient-reported outcome representative of the patient group as a whole. 962 participants were randomised, 478 in the measure of vitiligo treatment success. Br J Dermatol ivermectin arm and 484 in the metronidazole arm. 2016, 174: 386-394 Implications Outcomes measured were a reduction in lesion This tool is free and easy to use, and could be count, Investigator’s Global Assessment (IGA) and Context utilised in a clinical setting. Crucially it is a patient- patient-reported outcomes (a 5-point global scale, Vitiligo is a chronic skin disease causing reported outcome measure. The VNS can be satisfaction questionnaire and Dermatology Life depigmentation. A large number of RCTs have accessed at www.nottingham.ac.uk/research/ Quality Index (DLQI)). been undertaken and published assessing groups/cebd/projects/2vitiligo/vitiligo-outcome- treatments for vitiligo but the lack of standard measures.aspx and used with permission. Further Key fi ndings outcome measures ensures comparison of validation is required with a larger cohort of 93.8% participants completed the study. Baseline treatment effect is diffi cult. A measure frequently participants and with a wider range of genuine demographics were comparable in both arms of used is an estimation of ≥75% repigmentation (rather than digitally manipulated) pre- and post- the study. At 16 weeks lesion count had reduced but there is no validation of this and patient- treatment images. DN by 83.0% in the ivermectin arm and 73.7% in the reported outcome measures are rarely used metronidazole arm (p<0.001). IGA was reported in vitiligo studies. This paper aims to validate a References as clear or nearly clear with ivermectin 84.9% vs previously developed patient-reported outcome 1. Revuz J. Hidradenitis suppurativa. JEADV 2009, metronidazole 75.4% (p<0.001). Patient-reported measure, the vitiligo noticeability scale (VNS), by 23(9): 985-98 outcomes showed the global rating of excellent asking whether the VNS is a better and more 2. Spoendlin J, Voegel JJ, Jick SS & Meier CR. A study or good for ivermectin 76% and metronidazole consistent indicator of treatment success than % on the epidemiology of rosacea in the UK. Br J Dermatol 74.8%. Satisfaction ranked at 76% for ivermectin vs repigmentation. The VNS is a score of 1-5 with 1 2012, 167(3): 598-605 = more noticeable and 5 = no longer noticeable. 3. Whitton ME, Pinart M, Batchelor J, et al. 61.3% for metronidazole and DLQI reduced by an Interventions for vitiligo. Cochrane Database Syst Rev average of 5.15 in the ivermectin arm, 3.93 in the 2015, 2:CD003263 metronidazole arm. Methods 4. Jemec GB. Clinical practice. Hidradenitis Patient participants were recruited via a mailing suppurativa. New Engl J Med 2012, 366(2): 158-64 Adverse effects reported were mainly skin list, the Vitiligo Society and social media and 5. James Lind Alliance, 2013. Hidradenitis suppurativa irritation at a rate of 0.6% for the ivermectin dermatologists based in the UK who had Priority Sharing Partnership. Available at: www.jla. arm and 0.8% for the metronidazole arm. Three previously expressed an interest. There were 101 nihr.ac.uk/priority-setting-partnerships/hidradenitis- suppurativa [accessed 24.4.16] participants in the ivermectin arm discontinued patient responders and 33 clinicians. 6. Angel MF, Ramasastry SS,Manders EK, Ganfi eld D, treatment and 10 in the metronidazole arm. Pre- and post-treatment digitally manipulated Futrell JW. Benefi cial effects of staphage lysate in the images were used with participants responding treatment of chronic recurrent hidradenitis suppurativa. Commentary online using the Survey Monkey tool. Surgical Forum 1987, 38: 111-2 This study is useful as metronidazole has been Respondents were asked to give a global 7. Jones CW, Handler L, Crowell KE, Keil KG, one of the most used therapies in the UK to assessment of treatment success and a VNS. Weaver MA, Platts-Mills KF. Non-publication of large treat rosacea. This study demonstrates ivermectin Clinicians additionally were asked to identify % randomized clinical trials: cross sectional analysis. BMJ 2013, 347: f6104 as superior in all of the outcomes measured. repigmentation. 8. EMC. SPC Soolantra 10mg/g cream. Electronic A good safety profi le was demonstrated and Medicines Compendium, 2015. Available at: as it is for once-daily use it is easier to use than Key fi ndings www.medicines.org.uk/emc/medicine/30353 [accessed metronidazole. When comparing the VNS scores with global 25.4.16] treatment success ratings, crude agreement was 9. Taieb A, Khemis A, Ruzicka T, et al. Maintenance There is not a number to defi ne a large RCT7 but 78% for patients and 76% for clinicians. Crude of remission following successful treatment of this is often taken as more than 500 participants. This agreement by clinicians comparing % repigmentation papulopustular rosacea with ivermectin 1% cream vs. metronidazole 0.75% cream: 36-week extension of study had nearly twice that number of participants against global treatment success was 62%.. the ATTRACT randomized study. JEADV 2015, 30(5): and was multi-centred and multi-national indicating 57% patients reported the VNS very easy or easy 829-36

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