Interventions for hyperhidrosis in secondary care: a systematic review and value-of-information analysis

Abstract

BackgroundHyperhidrosis is uncontrollable excessive sweating that occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. The management of hyperhidrosis is uncertain and variable.ObjectiveTo establish the expected value of undertaking additional research to determine the most effective interventions for the management of refractory primary hyperhidrosis in secondary care.MethodsA systematic review and economic model, including a value-of-information (VOI) analysis. Treatments to be prescribed by dermatologists and minor surgical treatments for hyperhidrosis of the hands, feet and axillae were reviewed; as endoscopic thoracic sympathectomy (ETS) is incontestably an end-of-line treatment, it was not reviewed further. Fifteen databases (e.g. CENTRAL, PubMed and PsycINFO), conference proceedings and trial registers were searched from inception to July 2016. Systematic review methods were followed. Pairwise meta-analyses were conducted for comparisons between botulinum toxin (BTX) injections and placebo for axillary hyperhidrosis, but otherwise, owing to evidence limitations, data were synthesised narratively. A decision-analytic model assessed the cost-effectiveness and VOI of five treatments (iontophoresis, medication, BTX, curettage, ETS) in 64 different sequences for axillary hyperhidrosis only.Results and conclusionsFifty studies were included in the effectiveness review: 32 randomised controlled trials (RCTs), 17 non-RCTs and one large prospective case series. Most studies were small, rated as having a high risk of bias and poorly reported. The interventions assessed in the review were iontophoresis, BTX, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland (e.g. laser, microwave). There is moderate-quality evidence of a large statistically significant effect of BTX on axillary hyperhidrosis symptoms, compared with placebo. There was weak but consistent evidence for iontophoresis for palmar hyperhidrosis. Evidence for other interventions was of low or very low quality. For axillary hyperhidrosis cost-effectiveness results indicated that iontophoresis, BTX, medication, curettage and ETS was the most cost-effective sequence (probability 0.8), with an incremental cost-effectiveness ratio of £9304 per quality-adjusted life-year. Uncertainty associated with study bias was not reflected in the economic results. Patients and clinicians attending an end-of-project workshop were satisfied with the sequence of treatments for axillary hyperhidrosis identified as being cost-effective. All patient advisors considered that the Hyperhidrosis Quality of Life Index was superior to other tools commonly used in hyperhidrosis research for assessing quality of life.LimitationsThe evidence for the clinical effectiveness and safety of second-line treatments for primary hyperhidrosis is limited. This meant that there was insufficient evidence to draw conclusions for most interventions assessed and the cost-effectiveness analysis was restricted to hyperhidrosis of the axilla.Future workBased on anecdotal evidence and inference from evidence for the axillae, participants agreed that a trial of BTX (with anaesthesia) compared with iontophoresis for palmar hyperhidrosis would be most useful. The VOI analysis indicates that further research into the effectiveness of existing medications might be worthwhile, but it is unclear that such trials are of clinical importance. Research that established a robust estimate of the annual incidence of axillary hyperhidrosis in the UK population would reduce the uncertainty in future VOI analyses.Study registrationThis study is registered as PROSPERO CRD42015027803.FundingThe National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis

“…To our knowledge, no prior cost-effectiveness evaluations have been published for first line treatments of PAHH. A previous evaluation of second line treatment sequences for refractory primary hyperhidrosis, but this analysis did not include first-line topical treatments [20] The treatment benefit of GT over prescription aluminum chloride is driven by both higher response rates for GT and higher persistence to GT than aluminum chloride. While some patients respond to prescription-strength aluminum chloride, tolerability may be hindered by skin irritation, which is a common adverse event [1,43].…”

“…The aim of this study is to estimate the cost-effectiveness of GT as a first-line topical therapy option for the treatment of PAHH compared to topical aluminum chloride from a United States payer perspective. the most commonly used tool to assess severity of disease and treatment effects over time [20]. The impact of hyperhidrosis and its associated symptoms is measured on a four-point scale which correspond to model health states: HDSS 1 (least severe, described as "sweating is never noticeable and never interferes with daily activities"), HDSS 2 ("My sweating is tolerable but sometimes interferes with my daily activities", HDSS 3 ("My sweating is barely tolerable and frequently interferes with my daily activities", and HDSS 4 (most severe, described as "sweating is intolerable and always interferes with daily activities") [21] .…”

A systematic evidence-based review of treatments for primary hyperhidrosis

“…The following databases were searched: MEDLINE, Embase, the Cochrane Database of Systematic Reviews (CDSR) and Cochrane Central of Controlled Trials (CENTRAL). Studies were identified 1) by reviewing and assessing those included in two related publications by Wade et al of the same search strategy and results [11,12] (RoB) in any review domains renders the overall study as at high or uncertain RoB [14]. Our assessment is that this standard is quite stringent and insufficiently contextual, which may result in the exclusion of results that are possibly reliable.…”

“…A systematic review first reported by Wade et al in 2017 [11] and subsequently in Wade et al 2018 [12] examined relevant evidence available in the scientific literature through July 2016 for primary hyperhidrosis treatments. However, several aspects of that analysis, including the lack of special consideration for those studies utilizing within-patient designs or with large response rates, the exclusion of aluminum/zirconium compounds commonly used for hyperhidrosis…”

Interventional management of hyperhidrosis in secondary care: where do we go from here?

“…Despite advances being made in the treatment of hyperhidrosis over the last 100 years the availability of treatment options across the U.K. is not standardized. Current recommendations and practice are not based on strong clinical evidence . As we advance in an era of evidence‐based medicine with more involved patient choice, an in‐depth assessment of treatment studies is to be welcomed and this systematic review of hyperhidrosis is timely.…”