Authors' objectives: Hidradenitis suppurativa is a chronic inflammatory skin disease characterised by recurrent inflammatory lesions and skin tunnels in flexural sites such as the axilla. Deroofing of skin tunnels and laser treatment are standard hidradenitis suppurativa interventions in some countries but not yet introduced in the United Kingdom. To understand current hidradenitis suppurativa management pathways and what influences treatment choices to inform the design of future randomised controlled trials. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterised by recurrent inflammatory nodules, abscesses and skin tunnels in flexural sites including the axilla and groin. Flares are very painful, may produce pus and scarring and have a large impact on quality of life. Prevalence is about 1% of the UK population and HS particularly affects young adult women, detrimentally affecting relationships and employment. Multidisciplinary team (MDT) management is recommended, integrating drug treatments that reduce HS inflammation and surgery to manage scarring. A consensus process conducted by the Hidradenitis SuppuraTiva cORe outcomes set International Collaboration (HiSTORIC) defined outcome domains to measure in HS trials and validation of outcome measure instruments (OMIs) to assess each domain is underway. The Treatment of Hidradenitis Suppurativa Evaluation Study (THESEUS) addressed several questions prioritised in the James Lind Alliance Priority Setting Partnership (PSP) for HS, including what is the most effective and safe group of oral treatments in treating HS (ranked number one priority), what is the impact of HS and the treatments on people with HS (ranked third) and what is the best surgical procedure to perform in treating HS (ranked sixth). Deroofing is a surgical procedure usually performed under local anaesthetic allowing targeted removal of HS subcutaneous skin tunnels by blunt skin probing followed by removal of the tunnel roof and secondary intention healing of the base. It is routinely performed in several countries but not the UK. Laser treatment targeting the hair follicle is another well-recognised intervention for HS not currently used in the UK. The Treatment of Hidradenitis Suppurativa Evaluation Study was designed as a prospective cohort study to introduce deroofing and laser treatment for HS in the UK and to understand how conventional surgery and oral antibiotics are currently used. To understand current HS patient pathways and what influences patients’ and clinicians’ treatment choices to inform the design of future randomised controlled trials (RCTs). To determine the feasibility of recruiting individuals with HS into clinical trials. To fully characterise the THESEUS drug and procedural interventions. To test the feasibility and responsiveness of OMIs for HS trials. To explore consensus-agreed recommendations for future RCT study designs.

Authors' results and conclusions: Between February 2020 and July 2021, 151 participants were recruited, with two pauses due to the COVID-19 pandemic. Follow-up rates were 89% and 83% after 3 and 6 months, decreasing to 70% and 44% at 9 and 12 months, respectively, because pandemic recruitment delays prevented all participants reaching their final review. Baseline demographics included an average age of 36 years, 81% female, 20% black, Asian or Caribbean, 64% current or ex-smokers and 86% with a raised body mass index. Some 69% had moderate disease, 19% severe disease and 13% mild disease. Regarding the study’s primary outcome, laser treatment was the intervention with the highest proportion (69%) of participants who were eligible and hypothetically willing to receive treatment, followed by deroofing (58%), conventional surgery (54%), the combination of oral clindamycin and rifampicin (44%) and doxycycline (37%). Considering participant willingness in isolation, laser was ranked first choice by the greatest proportion (41%) of participants. The cohort study and qualitative study demonstrated that participant willingness to receive treatment was strongly influenced by their clinician. Fidelity to oral doxycycline was only 52% after 3 months due to lack of effectiveness, participant preference and adverse effects. Delays receiving procedural interventions were common, with only 43% and 26% of participants commencing laser therapy and deroofing, respectively, after 3 months. Treatment switching was uncommon and there were no serious adverse events. Daily pain score text messages were initiated in 110 participants. Daily responses reduced over time with greatest concordance during the first 14 days. The Treatment of Hidradenitis Suppurativa Evaluation Study established deroofing and laser treatment for hidradenitis suppurativa in the United Kingdom and developed a network of 10 sites for subsequent hidradenitis suppurativa randomised controlled trials. Between February 2020 and July 2021, 151 participants were recruited. Recruitment was affected by the COVID-19 pandemic and there were two substantial pauses which mirrored two waves of the pandemic in the UK. Outside these periods, a recruitment rate of 15–20 participants per month was achieved. Follow-up rates were 89% and 83% after 3 and 6 months, respectively, decreasing to 42% at 12 months, in part because pandemic recruitment delays prevented all participants from reaching their final study review. Baseline demographics of THESEUS participants were in keeping with secondary care HS patients, with an average age of 36 years, 81% female, two-thirds current or ex-smokers and 86% with a raised body mass index (BMI). There was a slightly higher proportion of non-white participants than the UK average, with 20% being black, Asian or Caribbean. Baseline disease severity again reflects the HS secondary care population, two-thirds having moderate disease, 19% severe disease and 13% mild disease. Regarding THESEUS’s primary outcome, laser treatment was the intervention with the highest proportion (69%) of participants who were eligible and hypothetically willing to receive treatment, followed by deroofing (58%), conventional surgery (54%), oral clindamycin and rifampicin (44%), and finally doxycycline (37%). Considering participant willingness in isolation, laser was ranked the first choice by the greatest proportion (41%) of participants. Final intervention choice mirrored the primary outcome, except the proportion choosing laser treatment was lower because it was offered by only 6 of the 10 recruiting sites. The cohort study and nested qualitative study results demonstrated participant willingness to receive treatment and final intervention choice were strongly influenced by clinicians. ‘My doctor recommended it’ was the most common reason (59%) given by participants for their final choice. Fidelity to oral doxycycline was only 52% after 3 months due to lack of effectiveness, participant preference and adverse effects. Continuation of clindamycin and rifampicin after 3 months was affected by the standard course being 10 weeks initially, reflected by only 30% still receiving treatment after 12 weeks. Delays receiving procedural interventions were common, with only 43% and 26% of participants commencing laser therapy and deroofing, respectively, after 3 months. Treatment switching was uncommon, with only five participants switching from laser and nine switching from deroofing. There were no serious adverse events reported. Those receiving doxycycline had modest improvements after 3 months in median International Hidradenitis Suppurativa Severity Score System (IHS4) score from 7 to 6, Dermatology Life Quality Index (DLQI) score from 6 to 3.5 points, Hidradenitis Suppurativa Quality of Life score (HiSQOL) score from 26.5 to 11.5 and pain NRS from 2 to 1. Small effect sizes are in part due to relatively low baseline disease severity in the doxycycline group. Corresponding score changes for clindamycin and rifampicin at 3 months were decreases in IHS4 score from 11 to 5 points, DLQI score from 14 to 10.5 points, HiSQOL score from 34 to 23 and pain NRS from 4 to 2. The variable timing of procedural interventions limited interpretation of efficacy data for these interventions with follow-up reviews fixed in time after recruitment. Daily pain score text messages were initiated in 110 participants and 100 returned at least one score. Daily responses reduced over time and the median duration of concordance was 36 days. A higher level of completion occurred in the first 14 and 28 days. Implications for health care Offering medical and non-medical interventions, THESEUS encouraged an MDT approach to optimise HS care. Training and equipment provided by THESEUS established deroofing as a surgical option, bringing the UK in line with other countries. Deroofing is a tissue-sparing treatment for tunnels and can also be adapted for acute flares, the latter being ranked second highest priority in the HS PSP. A need for deroofing is demonstrated by 1 million views of the THESEUS deroofing video. While laser and light hair removal treatment was already available in the UK, it was rarely used for HS therapy and THESEUS showed that it can be provided for HS within existing infrastructure. Use of HiSTORIC-developed OMIs for HS familiarised 10 centres with well-validated tools to monitor patient progress. Several OMIs are suitable for routine clinical care; for example, HiSQOL can be completed in the waiting area before appointments.

Authors' methods: Prospective 12-month observational cohort study, including five treatment options, with nested qualitative interviews and an end-of-study consensus workshop. Ten United Kingdom hospitals with recruitment led by dermatology and plastic surgery departments. Adults with active hidradenitis suppurativa of any severity not adequately controlled by current treatment. Oral doxycycline 200 mg once daily; oral clindamycin and rifampicin, both 300 mg twice daily for 10 weeks initially; laser treatment targeting the hair follicle (neodymium-doped yttrium aluminium garnet or alexandrite); deroofing; and conventional surgery. Primary outcome was the proportion of participants who are eligible, and hypothetically willing, to use the different treatment options. Secondary outcomes included proportion of participants choosing each of the study interventions, with reasons for their choices; proportion of participants who switched treatments; treatment fidelity; loss to follow-up rates over 12 months; and efficacy outcome estimates to inform outcome measure instrument responsiveness. It was not possible to characterise conventional surgery due to a low number of participants. Study design A multicentre prospective observational cohort study, including five treatment options, with nested process evaluation, including participant and clinician interviews, and an end-of-study consensus workshop. oral doxycycline 200 mg once daily; oral clindamycin and rifampicin both 300 mg twice daily for 10 weeks initially; laser treatment targeting the hair follicle: neodymium-doped yttrium aluminium garnet (Nd-YAG) or alexandrite; deroofing; conventional surgery, procedure and closure method as per site’s usual practice. Participants could choose their intervention subject to availability on discussion with their clinician, who advised on the suitability of the interventions, the shared decision-making process mirroring usual clinical practice. Participant choice was supported by a decision grid (https://www.cardiff.ac.uk/centre-for-trials-research/research/studies-and-trials/view/theseus) providing a description and head-to-head comparison of THESEUS interventions.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/17/98/01

Year Published: 2023

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/HWNM2189

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/HWNM2189

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk