Treatment of Hidradenitis Suppurativa Evaluation Study: the THESEUS prospective cohort study

Prioritisation of the research question

A James Lind Alliance Priority Setting Partnership (PSP) for HS produced a top 10 list of research questions in 2014, following a prioritisation exercise involving people with HS and their clinicians. 17 THESEUS was designed to improve the evidence base for several of the top 10 priorities 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).

The design of THESEUS was also guided by the funding call from the UK National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme, which posed the question: ‘What are the best management options for HS when first line treatments fail?’

The aims of THESEUS are to understand how HS treatments are currently used in the UK and to inform the design of future RCTs in HS.

Option 1: oral doxycycline

Oral doxycycline was offered at a dose of 200 mg once daily.

Option 2: oral clindamycin and rifampicin

Oral clindamycin and rifampicin were each taken at a dose of 300 mg twice daily as a combined course for 10 weeks initially, with the option to continue up to 6 months. Prior to commencing treatment, participants were required to have safety blood tests (full blood count, renal function, liver function) at baseline and repeated 4 weeks after starting the treatment, as per usual care.

Option 3: laser treatment

Laser treatment targeting the hair follicle was specified in the protocol with Nd-YAG laser (skin types 2–6) or alexandrite/diode laser (skin types 1–3). This treatment option was scheduled to be administered on four occasions, each 1 month apart.

Laser hair removal treatment was performed by healthcare professionals (HCPs) trained and certified in the use of medical lasers. Training in laser treatment is already formalised as part of medical laser training and certification was required for practitioners to be insurable. THESEUS did not provide study-specific training in laser treatment; however, a laser protocol was provided.

Option 4: deroofing of skin tunnels

Deroofing of skin tunnels was carried out using electrocautery and details of the procedure performed were documented in a clinical report form.

A protocol and training video was developed by the study team to guide HCPs (including dermatologists, plastic surgeons and other surgeons) through the deroofing procedure. HCPs wishing to use the procedure HCPs were invited to attend an in-person training event. The training video and an information video for participants were made available on the publicly accessible THESEUS study website (https://www.cardiff.ac.uk/centre-for-trials-research/research/studies-and-trials/view/theseus).

Deroofing procedures were performed under local anaesthetic in most cases and could be repeated if required. Details of the procedure were recorded in a clinical report form in each case. The total area treated at one time was limited by the volume of local anaesthetic needed and expected degree of impairment of activities of daily living during recovery. Wound healing took place by secondary intention healing over a period of a few weeks.

Option 5: conventional surgery

Participants selecting the conventional surgery option were assessed as to the most appropriate excision margins (narrow or wide). Skin closure following excision could also vary depending on which method the clinician felt most appropriate.

No formal training was provided for conventional surgical options because one of the objectives of THESEUS was to document current practice and assess any variability. A protocol was provided to surgeons, which contained some basic parameters, allowing for wide variation in practice. The surgical technique used for each procedure was documented using an online questionnaire.

Study objectives

The primary objective of the THESEUS study was to understand how HS treatments are currently used and to inform the design of future HS RCTs.

The secondary objectives of the study were to determine the feasibility of recruiting individuals with HS; to test the feasibility and responsiveness of OMIs; to understand current patient pathways and what influences patients’ and clinicians’ treatment choices; to fully characterise the study interventions (dose of medication, type of surgical techniques used); and to explore consensus-agreed recommendations for future RCT study designs.

Outcome measures

The primary outcome of THESEUS was to determine the proportion of participants who were eligible, and hypothetically willing, to use the different THESEUS treatment options.

The secondary outcomes included the proportion of participants choosing each of the study interventions, with reasons for their choices; the proportion of participants who switch treatments, with reasons for switch; study treatment fidelity; the loss to follow-up rates during the study; treatment efficacy outcome estimates after 6 months of follow-up, and to inform OMI responsiveness.

Site selection

Clinical sites were selected for participant recruitment based on their clinical services and experience in HS management. Sites with the following expertise were selected: (1) those that offered a multidisciplinary team (MDT) approach integrating HS medical and surgical care; (2) sites with experience in HS surgery; (3) dermatology departments that were experienced in HS medical management. Additionally, study sites had to offer at least four of the five THESEUS interventions.

Clinical site set-up

Between November 2019 and May 2021, 11 secondary care sites were identified to carry out participant recruitment. Ten sites actually opened to recruitment as one site had to be withdrawn because it was unable to provide capacity and capability approvals following the restart period during the COVID-19 pandemic. Site set-up and recruitment were staggered due to the pandemic, and not all 10 sites were open to recruitment simultaneously. Dermatologists or surgeons took the role of principal investigator in 9 of the 10 sites, and a GP working in a dermatology department undertook the role in 1 site. The local investigating team comprised research nurses, dermatologists, surgeons, specialist nurses and trial co-ordinators. Training was delivered to the principal investigators and the site research team in one site set-up session, usually via teleconference. THESEUS was a low-risk study following usual clinical practice. A risk-based approach to study monitoring was adopted and outlined in the study risk assessment document. The study was monitored centrally and there were no preplanned site monitoring visits.

Pain score collected via text message

The feasibility of collecting daily pain data using short messaging service (SMS) text messages was trialled in the THESEUS study. When a participant commenced their treatment, or first received their procedure, they were sent a text message asking the magnitude of their current pain, using the pain 0–10 NRS instrument. The messages would be sent to the participant for up to 12 weeks. The text to the participants read:

Hello. This a text message from the THESEUS study. Please indicate the level of pain you are CURRENTLY experiencing due to your HS. The scale is from 0–10. ‘0’ means no pain and ‘10’ means pain as severe as it could be. You have until 02.00 am tomorrow morning to return today’s pain score. If you no longer wish to receive these messages please text STOP to [telephone number]

The participant receiving the messages could withdraw from participation in the text messaging by texting ‘STOP’ directly to the message. They were not charged for the withdrawal text message.

The messages were sent by Esendex, a telecommunications service provider. This was an automated process whereby Esendex was instructed to send the same message to the participant at the same time, 6 p.m., each day, with responses accepted until 2 a.m. the following day. The series of messages were triggered by the addition of data/dates into the intervention case report form within the online database. The responses from the text messages were held securely within the Esendex servers.

Once text message data collection was concluded a command was issued from the THESEUS server to query the Esendex application programming interface and request the inbound participant responses (as SMS messages).

Three-, six- and nine-month follow-up reviews

Reviews 1, 2 and 3 took place 3, 6 and 9 months after recruitment, respectively. Sites were encouraged to collect data within a window of 2 weeks either side of the intended follow-up date.

Reviews 1, 2 and 3 included a clinical examination of the disease stage using Hurley Staging24 and a HS skin lesion count, documenting the number of inflamed nodules, abscesses and draining skin tunnels. The patient reported outcome measures collected at baseline were repeated at Reviews 1, 2, and 3, as described in Table 1.

Participants were asked questions related to the THESEUS intervention they had selected. If the participant had chosen one of the THESEUS procedures (laser, deroofing, surgery), questions would focus on receipt of the procedures and whether the participant was content to continue with the course of treatment. If the participant had selected one of the THESEUS antibiotics options, then questions would centre around adherence to the chosen medication and whether they would be continuing with the treatment.

Twelve-month follow-up review

The final review (review 4) took place 12 months after recruitment. Review 4 repeated the assessments performed at the previous reviews, including information about receipt of the intervention, fidelity of procedure delivery and treatment adherence, as well as the clinician- and patient-reported outcome measures. In addition, participants were asked to complete an end-of-study questionnaire, which contained multiple choice and free text responses aimed at understanding their experience of taking part in the THESEUS study, and their recommendations around future HS-based research.

Follow-up adaptations as a result of the COVID-19 pandemic

The COVID-19 pandemic limited the capacity for THESEUS sites to follow up participants in person and so a study amendment was submitted and approved to permit remote follow-up. Remote assessment was carried out by video call or telephone call. In the case of telephone calls, participants could send photographs of skin regions affected by HS by secure e-mail. In the absence of photographs, participants were permitted to provide their own count of active HS skin lesions, supported by guidance from their investigator during the telephone call. The method of lesion count assessment was recorded in each case.

Adverse events

THESEUS was a low-risk observational study, and the adverse event reporting procedure was developed to reflect this. As such, adverse events that were not deemed to be related to any of the study interventions were not reported. Local investigators were encouraged to follow their usual processes for reporting adverse events (e.g. yellow card reporting) when required.

Adverse events that were, or could be, related to the study procedures or treatments were recorded in the THESEUS adverse event reporting form or in the Intervention case report forms at the routine review appointments. The adverse event was described in a free text box in the case report forms.

Study withdrawal

Participants could withdraw from any aspect of the study, at any time, without giving an explanation. If a participant wished to withdraw from the study a withdrawal form was available on the THESEUS online database. The participant could also withdraw from text messages directly by texting ‘STOP’. Using the online form, the participant could withdraw from the following elements of the study: THESEUS treatment(s), text message pain scores, study data collection (choice of complete or partial withdrawal), withdrawal from being contacted about the interview study and consensus workshop.

Sample size

A sample size of 150 participants, permits estimation of the proportion of participants who are hypothetically willing and eligible to be randomised in a clinical study to within a 95% confidence interval (CI) of ±7%. We also wished to identify the case mix of patients for each of the possible treatment options. From our patient survey, the least favoured treatment option (13%) was minor surgical procedures. A total of 150 patients would provide us with 20 patients opting for each of the non-medical interventions, which is sufficient to explore delivery in an IDEAL 2b evaluation. The IDEAL 2b framework for the evaluation of surgical interventions outlines a process of innovation, development, exploration, assessment and long-term study. 30 Stage 2b refers to the exploration stage in evaluating new surgical techniques.

Introduction

A systematic review from 2021 found that no qualitative studies of the experiences of people with HS had been conducted in the UK. 34 The review found studies in Ireland, USA, Denmark and Israel. 34 Most studies focused on the impact of symptoms and psychosocial adjustment. Studies suggest there are widespread physical, psychological and social impacts of HS on an individual, and that stigmatisation that leads to shame is a key factor driving distress and coping strategies. 35 To a more limited extent, studies also investigated patient perspectives of health care and treatment for HS, which together indicate that HS patients’ needs are not being met by healthcare systems. 34 As the THESEUS study was broadly reflective of UK current practice and treatment pathways, it was an ideal setting to explore patient and healthcare staff perspectives of HS care and treatment within the UK. This can help us better understand patient experiences of current treatments and inform the design of future clinical trials.

Study aims and objectives

Methods

Participant selection

The sample was taken from the group of THESEUS cohort study participants who agreed to be contacted about the interview study using a purposeful sampling framework (Table 22).

Study procedure

Semistructured interviews took place via telephone and were audio recorded. At the start of the interview, consent was taken verbally. The interviews ranged from approximately 30 minutes to 75 minutes, with most taking around 60 minutes. A topic guide covered: (1) treatment experiences prior to the study; (2) treatment experiences during the study; and (3) experiences of taking part in the research study. A debrief at the end of the interview advised participants where to go if the interview had raised any concerns or questions about their care.

Research team and reflexivity

The interviewer was a female psychologist and postgraduate researcher (LH) who had previous training and experience in qualitative research and was also supervised by an experienced qualitative researcher (PL) with regular opportunities to debrief. The interviewer had no previous involvement with participants prior to the interview study. As the interviews were being conducted by the THESEUS study team, participants were regularly encouraged to share both positive and negative experiences of the study. Findings were discussed periodically with the multidisciplinary SMG to adapt design as necessary (e.g. agreed to adapt the topic guide to explore the impact of COVID-19).

Analysis

Interviews were transcribed verbatim and managed in NVivo 12 (QSR International, Warrington, UK). 36 A prespecified thematic framework was used to code data, and the framework was refined during the coding process to capture pertinent, unanticipated topics. This coding was then reviewed by the interviewer and sections of coded data were reviewed by a second author (PL) and refinements were discussed. The interviewer then looked at framework matrices to understand and interpret the data, which resulted in three final themes. Findings were discussed periodically between LH and PL during the analysis process. The three themes were then presented alongside illustrative data to a wider group of authors to view the findings from different methodological, clinical and patient perspectives (KT, JI, AB and CM). These discussions helped to develop key learning points for future HS research and clinical practice and fed into the THESEUS consensus workshop discussions (see Chapter 7).

Sample size

We aimed to recruit up to 50 participants taking part in THESEUS for interview, but data collection was deemed sufficient to answer research questions earlier than anticipated.

Participant selection

We aimed to interview up to 10 site staff (one per site) involved in delivering THESEUS. They could be involved in delivering any aspect of the study at any point. We did not include members of the SMG. A purposeful sampling approach was used to speak to individuals with different roles. The end-of-study questionnaire for site staff also contained open-text questions.

Study procedure

Interview participants were contacted by e-mail or telephone by the interviewer (LH or PL) to arrange a time and date. Participants were then sent the participant information sheet and a form containing all the consent statements (via e-mail) and asked to complete this ahead of the interview. Interviews ranged from approximately 20 to 40 minutes. The interview was semistructured.

Analysis

Findings were mapped to the same three broad themes as the patient data to aid comparison across data sources, but subthemes were tailored using a more inductive approach.

Open text from end-of-study questionnaires

The THESEUS participants and staff were able to submit open-text responses (questions in Appendix 1) as part of end-of-study questionnaires that were mapped to the same frameworks indicated above.

Participant characteristics

Thirty-five patient interviews took place between December 2020 and October 2021. Twenty-five (71%) participants were female. Participant ages ranged from 19 to 67 years. Those under 40 years accounted for 69% (n = 24) of the sample. Participants described their ethnicity as white (n = 23, 66%), mixed/multiple ethnic groups (n = 2, 6%), Asian/Asian British (n = 5, 14%) and black/African/Caribbean/Black British (n = 4, 11%). One participant did not state their ethnicity. Treatment choices were doxycycline (n = 6), clindamycin and rifampicin (n = 7), laser (n = 9), deroofing (n = 7) and conventional surgery (n = 6). At the time of interview, not all had received their baseline treatment choice (laser n = 2, deroofing n = 1, conventional surgery n = 4). Participants were from eight different sites.

Eight staff interviews took place between January and March 2022. We interviewed people with a range of roles and each from different sites.

There were 61 patient responses and 26 healthcare staff who provided open-text responses to analyse in the end-of-study questionnaires.

Framework matrix

The final framework matrices are in Appendix 2. The patient interview matrix includes 67 codes that were ordered hierarchically into three levels (codes, subcodes and further subcodes). The main codes were: (1) beliefs and experiences; (2) study treatment experiences; and (3) HS research experiences. ‘Beliefs and experiences’ covered beliefs about HS, beliefs about HS treatments and experiences seeking treatment. ‘Study treatment experiences’ covered reasons for treatment choice, treatment processes and satisfaction with treatment. ‘HS research experiences’ covered reflections on the study and recommendations for future research. The staff interview matrix includes 17 codes that were hierarchically coded into two levels (codes and subcodes). The three main codes were adjuncts to the three main codes in the patient interviews.

Final themes

Through a process of charting and mapping, final themes were developed that provide an interpretation of how the data answer our research questions.

Doxycycline

Doxycycline was typically preferred when individuals had limited experiences with HS (e.g. had not tried many treatments for HS). It was described as a ‘starting point’ and less invasive than surgical options.

So, start you on that one first and obviously when I go back [ … ] I will say, not that one, so then we will look at the other options.

(Participant 25, white male)

Sometimes there had been experience with other treatment options, but it was not perceived as the correct time for them to have surgery (e.g. still healing, not required for symptoms).

No, that’s what we both agreed was right at the time, mine’s not quite an advanced HS. I’ve had a few where they’ve had to be removed via surgery, but other than that I’ve been quite stable over the last 15 years of it.

(Participant 9, male, white)

Some information was new to individuals, and it was via interactions with HCPs that they had developed these perceptions of the treatment. Some were interested in the laser treatment, but it was not available at their site, or their doctor had encouraged them to start with the tablets first.

Clindamycin and rifamycin

Previous non-favourable experience of taking other tablets, including doxycycline and other similar drugs, led people to believe that they would not work for them again and so had a strong preference to try something new.

It was using the treatment grid and basically the first one was doxycycline, which is basically the same as lymecycline, which I’d been taking, which didn’t really seem to make an awful lot of difference either. So, we ruled that one out because I’d already been on that one. That’s why we went for the second one, because I thought there’s no point in wasting time doing something I’ve already taken that’s not really been effective. So, that’s why I chose the clindamycin and rifampicin.

(Participant 7, female, white)

Some were concerned about using medication (or taking more medication), particularly in the long term, but it was considered a necessary trade-off to stop symptoms. Reasons it was chosen over other options are that it was less invasive, participants had a lack of familiarity with other treatment options, concerns about what other options would entail or other options (e.g. laser, deroofing) not being available at their site.

Participant 6, female, white: I don’t think the deroofing would help.

Interviewer: Okay can you say why you think that’s the case?

Participant 6: I don’t understand what deroofing is. Sorry. […] I’m not a hundred per cent sure what it is or what it does or what it means.

The treatment grid was referenced when deciding not to ‘jump’ to surgery and give the tablets a try first. Sometimes patient initial treatment preferences were overridden by the treatment choice reported as what the doctor felt was most appropriate.

Yes, it’s not like I chose, she said this might be the way to go and I thought I’ll go with it, because I’d asked about surgery for my groin and she wants to try this first, because obviously it’s a very invasive treatment to get surgery. But because I had such positive result I’m quite pro surgery, I know it’s going to sound terrible, but I just go with what she said.

(Participant 15, female, white)

Laser

Laser was the most popular choice within the cohort. Past experiences left individuals unsatisfied by other options. Some felt that tablets had not worked for them, did not want them long term, had caused side effects they could not tolerate or worked to some extent but were looking for something to improve beyond what they could offer.

The two tablets, I mean for me in my head I was just like I have tried tablets already and I know what that means. That’s not really a long-term solution, I can’t just take tablets for my whole life.

(Participant 32, female, black/African/Caribbean/Black British)

One person ruled out tablets due to wanting to get pregnant. There was sometimes a push away from surgery if that had not gone well for individuals in the past or they were viewing it as more invasive.

It was perceived as a preventative measure as hair removal potentially prevents future boils, and many favoured this as a solution that was addressing the cause. It was also known to some that it was ‘new’ to the NHS, and so it had the added draw of being a chance to try a new treatment that was usually unavailable.

And the laser had just become available on the NHS for this, because obviously it is an infection of the hair follicle, so if can stop the hair follicle from growing, it’s hoping we can stop the boils. That’s why he is going for the main bits where they are really, really bad at the moment.

(Participant 27, female, white)

Some of the reasons for preferencing laser came from doctors or information provided within the study.

Not much to say it was just the [unclear 0:33:20.1] your two surgeries didn’t work I don’t know if a third surgery is going to help you let’s try a laser treatment to you know try and get rid of the hairs that may be causing the inflammation because it’s got HS has got to do with sweat glands so if we limit the what’s called the inflamed hairs it could also limit the amount of legions that show up. Which was a good sort of theory so I was like okay I’ll go with that it’s not too invasive sort of thing and hopefully over time it would reduce, if not reduce [unclear 0:33:57.5] which me sounds good so yeah, that’s how we came to that sort of conclusion.

(Participant 20, male, black/African/Caribbean/Black British)

Deroofing

Some had heard of deroofing previously, but often HCPs and study information were the primary sources of information. For those that had seen other sources of information, there was an experience where online information made it seem highly effective, whereas another where online forums made it seem like a ‘temporary fix’.

There were concerns about deroofing, and surgery more generally, but it was considered a necessary ‘last resort’. Reasons were that medication did not work effectively enough for them, caused them unwanted side effects and they had concerns about long-term use. One person preferred deroofing over laser due to previous facial hair laser removal resulting in bumps in their skin.

I mean I am kind of limited because I have never really tried, I tried one of them, I know it’s some sort of cycline on the list but it doesn’t work for me and for me laser is a no-no.

(Participant 29, female, ethnicity not reported)

There were initial preferences for other treatments, particularly laser and conventional surgery, but a HCP had advised them to use deroofing, citing that laser would not remove the HS, only the hair follicles, and that deroofing is a shorter, simpler procedure than conventional surgery. Often this came with a promise to consider other options in the future.

I saw that the laser sounds good, I don’t know why I thought that. Then after speaking to the consultant the sort of said, well it’s not the best option because it just removes the hair follicles, it doesn’t remove the HS itself. They said that deroofing would be a better option, so I said, okay I’ll for deroofing.

(Participant 18, male, white)

Others did not realise that they had a choice or did not feel like they had a choice, and that they had to go with the HCP’s opinion, and others said they worked it out together with their professional. Some people wanted guidance from their professional due to finding it a difficult decision with limited information.

I did yeah, but he said it’s quite a disfiguring operation, so the deroofing would be best to start off, and then later on down the line if I was really adamant about wanting the other surgery then he would consider it. […] I didn’t have any choice, I felt like I had to go with it.

(Participant 2, female, Asian/Asian British)

Conventional surgery

Conventional surgery was the least popular choice within the cohort. Some had previous experiences of using it and felt they knew it worked and knew the process, so wanted to stick with it. It was often chosen because other options were not considered appropriate. Of particular interest is why it was chosen over deroofing as the alternative surgical option. Reasons given were that deroofing was only appropriate for HS that appears in the same place each time, seemed to be deeper so they felt may be riskier, the video was scary and they did not like the idea of being awake for the procedure.

I Googled that video and that was horrendous. […] This person was awake on the surgery bed, admittedly probably had anaesthetic, like local anaesthetic, so that’s why they were awake. There was the smell of burning skin when you’re awake, how can anybody go through that. I said to the plastic surgeon I was please do not ever advise for me to have deroofing, I really don’t think I could do that unless I was asleep.

(Participant 21, female, white)

For some, conventional surgery was chosen alongside other options (e.g. having deroofing on different areas, having laser first or having medications as well). HCPs’ advice on which was more appropriate informed choices.

Model of treatment choice process

There were patterns across all participants in how treatment choices were reached (Figure 5). Individuals had experiences and knowledge (e.g. past treatments, healthcare interactions, online information) that shaped their beliefs about HS and HS treatments. These could be described as push and pull factors, indicated by the upwards and downwards arrows, that helped individuals choose between treatments. Beliefs informed preferences, which informed treatment choice.

FIGURE 5.

Model of treatment choice process in THESEUS study.

However, study interactions could also influence choice. In some cases, there was strengthening or creating of beliefs and preferences via information shared from the HCP and study materials. For example, participants perceived a hierarchy between the THESEUS treatments, which was likely created or reinforced by study materials and communication with the study team (e.g. the study treatment grid, see Chapter 6).

I guess I’m going by the grid, so it’s kind of like the oral treatments first, then it’s laser hair removal, then it’s like the wall surgery type things. So, what I think I will do is probably just go through them and see what works best. Obviously the major surgery being the last resort, rather than jumping. If I feel a need to jump then obviously I will.

(Participant 7, female, Asian British)

In other cases, they directed treatment choice away from initial preferences. HCPs could have a very influential position, with some patients reporting that they went along with what the professional thought was the best option for them. However, there were others who felt they were left to make the final decision. Some patients felt this was too much responsibility or a particularly hard decision for them and had hoped for more HCP guidance.

I might have, if this hadn’t been an alternative, if she’d said, oh you have to go to laser surgery, you have to. I would have done that. I think I’m going to go with my doctor, I’m no specialist in this field. I just have the disease.

(Participant 15, female, white)

Staff perspectives on treatment choice

Some staff were particularly interested in certain treatments included in the study. Preferences among their patient population were also noticed. Laser was appealing as a new treatment avenue not currently available in routine NHS care and the low risk. Deroofing was described as a new approach for treating HS, but staff undertaking the surgical procedures had experiences of using similar approaches. Some centres noted that a lot of patients had already tried antibiotics and so were not keen to take these, whereas others found they were the most appropriate treatments for new patients and individuals worried about surgery. Some staff described a process of guiding a patient’s treatment choice based on eligibility criteria and what they felt was most suitable clinically.

So, when a lot of these patients come in to dermatology they’ve usually tried antibiotic treatments and they’re looking for something more really, and they’ve tried the antibiotics, and I did find when they chose what intervention they wanted based on what we told them and what we’ve informed them, they were very, very keen on trying perhaps the laser, depending on obviously how severe their condition is, but they were very interested in it because I think it’s not offered on the NHS at the moment, so that was one treatment we found that they were particularly interested in.

(Staff member 4)

It was noted that other than the new availability of some treatments, the study had little effect on prescribing practices, as it fit naturally with current care pathways. However, regular care often uses medical and surgical treatments, and treatment would vary over time due to flaring nature of the condition, rather than choose between them. It was noted by one prescriber that it perhaps encouraged use of doxycycline instead of lymecycline. Practices were also commonly prescribing adalimumab, which was not part of the THESUES framework.

They kind of fit in with what we would have been doing clinically anyway, so I didn’t find them difficult to choose, they were the natural choices.

(Staff member 1)

Antibiotics

Few pretreatment issues were reported, although some reported barriers accessing tablets (waiting for a prescription or not having access to them when not at home). There were also difficulties in taking the tablets (e.g. remembering to take them) and people often adjusted when they took them to help them remember and to limit adverse effects (e.g. take with food, not before bed). Some people experienced adverse effects, whereas others did not. Upset stomach or diarrhoea were reported for doxycycline and stomach issues, diarrhoea, orange urine, pain in ear, impact on menstruation were reported for clindamycin and rifamycin.

I struggled at first. It was like you’ve got to take two of this tablet, one of this tablet and then another one of them tablets and two of them tablets and it’s a lot to try and remember every day and then the side effects of the two different tablets in your body threw me for six.

(Participant 6, female, white)

Some continued to use the antibiotics despite side effects and often noticed that the adverse effects improved with time, whereas others stopped using them, often advised by their doctor. Adverse effects impacted people’s work or were considered only manageable as they were working from home. Many people experienced an improvement in their HS while taking the tablets, although for some this was not maintained once stopping treatment. Others did not feel that there was a noticeable difference in their HS.

So, I was maybe missing one of the doses or I was going for a few days without taking them, because I just wasn’t timing it right to get the whole empty stomach thing happening. I noticed I was starting to get a bit of pain coming back, so starting to feel, so before I get a flare up I can feel it inside, sort of like a pulling, like a tension. I know when I start to feel that, that I’m going to start to get a flare up, it must be like something coming in the surface. When I hadn’t been taking the tablets properly I started to get that sort of – it was really weak but I could feel that sort of happening. I’ve been back on the tablets like I should have been for a good five, six days now and that’s gone. So, it’s definitely preferable from the side effects to tablets to the HS. Again, because I’m working from home and everything just now, any sort of side effects are manageable, but if it was normal times, it might be a bit different. But for what I’ve got just now, it’s manageable.

(Participant 24, female, white)

For some people a review was planned for after the course had ended, but others did not know what would happen once the course had come to an end.

Laser, deroofing and conventional surgery

For some there were significant delays to receiving laser/surgical options. The COVID-19 pandemic was often recognised as a contributing factor to these delays, but it could still be frustrating. Ahead of procedures, people reported feeling nervous about pain during the procedure and concern about wound healing after the procedure.

Oh I was constantly anxious, is it going to hurt? Is it going to work? Like what’s the lady going to be like doing it, it was all just loads of stuff. I got really, really bad anxiety and it was just a mixture of everything.

(Participant 27, female, white)

For laser, people described the experience as not being as painful as expected and there was little to no healing time required. Some had been concerned about pigmentation, due to having dark skin or due to it being on a noticeable part of their body, but this had not been experienced.

No I thought I might be a bit red and stuff but there was none of that. It wasn’t painful afterwards I was still like able to do normal things as well, I haven’t had any issues there. No, it’s been fine since. […] But I mean it hasn’t really, in terms of the actual pigmentation, like I haven’t noticed it on my skin. So yes, that’s okay for me now.

(Participant 26, female, Asian/Asian British)

Some had noticed drastic changes in their HS after the first or second treatment. There were concerns that four sets of treatments would not be enough to rid of all the hair in the area and that future treatments would be required, but this would not be available on the NHS.

After the first two treatments, as weird as it sounds, I felt a hell of a lot more comfortable from where the old then scar tissue and that was, where it used to flare up the worst. Yeah, it seemed to calm it down even my wife at the time said the area seemed a lot less angry and red than what it was so, since the laser treatment it’s worked wonders personally.

(Participant 34, male, white)

Healing times for deroofing were variable. For the surgery, people described not feeling any pain until after the anaesthetic wore off. Some people were pleased with the results of their deroofing and were surprised how effective it had been and how easy the healing process had been.

No and it hasn’t been, it hasn’t been so invasive like other surgeries that I’ve had you know it’s, I don’t feel as if I’ve had anything done but I’m not having any problems anymore with the two areas that they’ve done which was always you know there wasn’t a day that it wasn’t sort of enlarged and leaking but at the moment I’m going to touch but it seems fine.

(Participant 1, female, white)

Some were not satisfied, which seemed to be because the procedure had not been done as it should be, because they felt that all the HS had not been successfully removed or that their wounds were more challenging to deal with than the HS itself.

Because it was cut underneath along the line of the tunnel and the underneath part was scraped out and the skin left on. Meanwhile deroofing is meant to take out, it’s a tissue saving surgery, so it’s meant to take out the skin and scrape out whatever is in there, it’s fills back nicely. But the skin was left over this one and it started getting infected right from the third day. It’s healed now, well it hasn’t healed completely it’s still not healed inside because the whole idea is for it to heal from inside out, but because the skin was still on top of it, it was over-granulating and it was healing from the outside first.

(Participant 13, female, black/African/Caribbean/Black British)

We have little information on conventional surgery experiences due to delays in procedures taking place.

Staff perspectives on treatment experience

Laser and surgical procedures were not always available routinely by the teams within THESEUS, and so expertise had to be outsourced and buy-in from other specialties and departments was needed to conduct the study, which was sometimes challenging. Deroofing was reported as mostly straightforward to conduct. However, there were a few concerns reported, such as one surgeon wishing they had the opportunity for loop diathermy technical training and one surgeon warning of the potential harm of deroofing done without expertise if the sinus tract is very deep. Some thought that dermatologists could be trained to deliver this technique, but perhaps they might require more training needs. The intensity of deroofing wound care was also raised. As was the psychological care patients needed alongside medical and surgical treatments (e.g. weight management, smoking cessation, pain management, individual complexities/issues).

One has to be slightly careful with this technique, in that it’s like using a hot wire on butter, and some patients with HS have got very deep sinus tracks that get into levels of anatomy where a hot wire through butter isn’t really the effect you want to have.

(Staff member 7)

It was noted that one patient had to stop laser due to a flare up and risk of taking the medication for the flare at the same time as laser.

Positive experiences of laser or deroofing treatments within the study had led staff to want to continue them beyond the study, but many cited commissioning challenges were likely to prevent this change in practice.

Why people take part in hidradenitis suppurativa research

People recognised benefits both for themselves and for others with HS; as one person described it, ‘a win–win’. Some people wanted to learn more about their own condition. Some wanted the findings of the study to raise awareness among others. Some felt by taking part they could help find better treatments/a cure for others. While as a research team we are aware that people may cite socially acceptable responses for participating, there also seemed to be drivers relating to own challenging experiences with HS, and a belief that other people with HS might not feel able to, or do not have a diagnosis, to be able to take part in a study. People also talked about feeling ‘selected’ for this opportunity. Sometimes family members would encourage individuals to take part.

So, if I can help find a cure, I don’t mind being the guinea pig, so to speak, that’s, to me, it’s not really an issue. I’d rather try, like, I’ve got nieces and I’d hate for my nieces to go through what I had to go through and if I’m one of the people who can try things, why not?

(Participant 11, female, mixed/multiple ethnic groups)

Another reason for taking part was to gain access to treatment or support. Reasons reported were beliefs it would help them access surgical treatments quicker, access to laser that was not routinely available, beliefs it would provide extra support and time from NHS staff.

Because I found out that people who take part in the study get a bit more attention and I just felt like I needed the kind of extra attention, because the infection was really, really bad and I didn’t feel well […] My sister is a doctor and she said if I joined this study then I would probably get the extra attention from the doctors.

(Participant 31, male, black/African/Caribbean/Black British)

There were others that took part due to a reassurance that it would not influence their treatment or if they felt that the treatment as part of the study would be of minimal risk to them. People felt the study was a chance to do something about their HS and that taking action was better than doing nothing.

Many people were willing to take part in future research, often for the same reasons why they took part in THESEUS, but also some cited satisfaction with their experience in THESEUS.

I just think that I have had massive benefit from this one so I would definitely be mining to look for another one, I would be interested in knowing more about another one, but obviously it would depend on what the treatment options were but yes I would certainly consider it.

(Participant 30, female, white)

Study procedures

Remote appointments

There were a range of experiences of having all appointments face to face, all on the telephone or a mixture of both and it was not always clear if participants referred to THESEUS study or general healthcare appointments. Recruiting sites played a role in how appointments were delivered, with participants from at least two sites only being offered the face-to-face option.

Perceptions of the usefulness of remote appointments varied between participants. Some people valued that they did not need to travel if they were only going to be answering questions. Some also reported it as a more personal touch than the alternative of answering questions online or on a paper form.

I suppose because a lot of it is more convenient now anyway because of the whole telephone conversations in the sense that I wouldn’t have to go somewhere, you know what I mean? Like I wouldn’t have to drive to like a university to sit down and have this talk or something, so because a lot of it can be done over the phone I was pretty happy to take part.

(Participant 29, female, ethnicity not reported)

Others reported concerns around examining the HS as photographs could not fully capture the lesions or they could not explain the HS fully using language.

I found them a little bit different from the face to face. You know when they are face to face they can see me and look at my skin condition but on the phone sometimes I find I have a language problem if I am speaking to my English doctor, then I have a language problem about explaining my… Well when they look at me they know what they are looking at, but that’s why I found it a little bit different, the phone and seeing the doctor.

(Participant 28, female, Asian/Asian British)

Remote appointments could also present logistical challenges including landline and broadband access, ringing a family member rather than patient’s number, participant expecting a telephone call while the team were expecting them to attend the clinic. Some spoke about uncertainty about whether their upcoming appointment would be face to face or not.

The COVID-19 pandemic had an impact on people’s experience and perception relating to remote appointments. Some were nervous to attend the hospital, particularly if they had bad experiences of COVID-19 infections or were concerned about their risk with other health factors. Some were concerned about being a burden on the healthcare system and were unsure if they were able to see a doctor. Some had face-to-face appointments cancelled or rearranged because of COVID-19.

It would mean I would have to get a train down and with the current situation with COVID I said that I’m not happy with doing that after being as ill as I was with COVID. I don’t want to put myself at any risk. So, they agreed to a telephone consultation, however the doctor didn’t call it was someone else from her team that called asking why I wasn’t in clinic. I explained, so that was probably just down to communication and disorganisation really.

(Participant 7, female, Asian British)

Photographs of hidradenitis suppurativa

Photographs were not a part of THESEUS study procedures, and not everyone had experienced taking photos of their HS, but some had them taken by medical photographers when they had treatments and others had taken them themselves for their own use or to share with HCPs.

Some people had a strong emotional reaction to the idea of photos of their HS, with it mostly being described by individuals as being embarrassing. One person described the idea of taking photographs of their HS as being ‘disgusting’. Other participants were less bothered by the idea, and willing to do it if necessary. One person described it as being just an armpit. Photos were particularly viewed as embarrassing or inappropriate when it was photos of the groin area.

For those who were embarrassed, there was only one person who preferred to take and send a photo themselves, whereas most people were concerned about the security of this. Concerns were around the permanency of the photos and the potential for error in sending them online.

Right, I’m going to be honest, some are on my groin and my bottom, my vagina, they are everywhere right. […] It’s like that’s there forever they can look back on that. I know that sounds funny, but it’s just a permanent record of it. I really wouldn’t feel comfortable. I’ve taken a picture of the ones under my arms and that was fine.

(Participant 15, female, white)

Photos were seen to have benefits in self-tracking, such as showing to your doctor or seeing the physical changes over time. One person described photos not being a full picture of their HS due to the need to feel the skin as the HS was not visible on the surface of the skin. Some people talked about the challenges of taking photos themselves. One person described not capturing all the lesions, just the main ones they could see. Some people had family members who could take some of the photos for them, but others did not.

It depends really, so yes. I think when I tell you guys I’ve got about 15–20 lesions or whatever you call them. They are in a mix place, mixing where I can take photos of them technically. But wherever they are, when they are there, I don’t know even know half the time. Like yesterday a new one came up and another one disappeared. So, taking photos of them, when I have to show it and all that, I actually just show the main ones, which is pretty easy for me to take photos of.

(Participant 19, male, Asian/Asian British)

Measurement of research outcomes

Staff perspectives on research experiences

The study procedures were often reported as straightforward, but there were some complaints about the database and the time-consuming, repetitive nature of the case report forms. Timely communication with study co-ordinating centre was reported, although a few unanswered queries raised during interviews. It was also noted by one participant that keeping communication to ‘essential’ was helpful. There was a strain on individual staff members time, and a research nurse or clinical fellow who can do a large amount of the study tasks as opposed to the consultants were seen as a good set-up for NHS research. It was clear that there were passionate individuals that made THESEUS happen in a challenging climate (including COVID-19 disruption, waiting list backlogs and busy staff schedules).

Basically there’s not really enough time or money to do all the things that we want to do, and that includes research, so the more that can be given to the dedicated research nurses, the better, so then the smoother it is, the more flexibility there is for patient visits, all that kind of thing.

(Staff member 2)

Staff were generally supportive of future research, and felt that it was necessary to meet needs of HS patients. There is a desire for more licensed treatment options so that more options can be offered to patients. There was a recognition that HS treatment may need to be different for subgroups/individuals.

Some of the next steps for future trials suggested were head-to-head biologicals, deroofing alongside biologicals compared with biologicals alone, long-term use of antibiotics compared with earlier introduction of biologicsal, dapsone, further evidence for laser or deroofing if they show promise. Aspects of deroofing research mentioned were use of general anaesthetic, wound care approaches and comparisons with conventional surgery. There was also a need for evidence around lifestyle factors and psychological support. The cost of interventions as well as their effectiveness was noted as important for NHS commissioning.

Randomised studies were considered more challenging for recruitment, particularly for surgical treatments, but experience of recruiting for randomised studies, thoughtful design (i.e. short wait if taking placebo or standard therapy) and the right combination of treatments included, meant staff members felt it could be feasible. Large long-term observational studies were also suggested.

The HS community was seen as a relatively young and motivated group that is interested in participating in research, but as many are of working age, work commitments were also noted as a challenge. There was also a need to be flexible to meet different patient needs, as it is a population that might be requiring extra support, especially during flare-ups and travel distances for care. There was also a concern about ensuring equitable and fair access to take part in research across different locations rather than just specialist centres.

Data collection on procedures

Treatment protocols produced for THESEUS treatments can be found in Appendix 3.

Site staff undertaking procedures were asked to complete a proforma that described aspects of their procedure. These included before, during and after operative procedures in line with the protocol.

Analysis was conducted in STATA. Analysis was exploratory in nature and provided descriptive summaries of the procedures undertook as part of THESEUS.

Creation of training videos for future studies

It was originally conceived that a proportion of THESEUS procedures would be videoed, which would allow us to identify areas of best practice to create training videos. However, it was identified that a training video for deroofing was required for sites within the THESEUS study, so the deroofing training video was created ahead of the study procedures and the HCP version has been viewed more than 1 million times (https://www.cardiff.ac.uk/centre-for-trials-research/research/studies-and-trials/view/theseus). There were challenges with some sites producing videos of laser procedures due to safety concerns, but plans are under way to produce a laser training video.

Laser

A total of 196 laser procedures were analysed across 56 participants. The number of laser treatments per participant is shown in Figure 6. The protocol stated that individuals should receive at least four sessions but procedure numbers for participants varied from one to nine within the data set.

FIGURE 6.

Number of laser treatments per participant.

The treatment protocol stated that follow-up laser procedures should be conducted within 28 days since the last laser treatment unless there is a reason relating to patient fitness or clinical discretion not to do so. The data returned suggested that follow-up procedures were not always conducted within the 28-day window. Reasons reported were often attributed to participant choice or ‘other’ reason (COVID-19 related, feeling unwell, appointment times and availability, life commitments or holidays, not attending or cancelling appointments or in one case was an extra treatment). In only one case, it was attributed to clinical advice, as the patient had COVID-19 at the last appointment.

A total of 74 (37.76%) procedures were reported as involving treatment fields being marked and photographer prior to the treatment session; 114 (58.16%) did not mark and photograph treatment fields and 8 (4.08%) were missing.

Table 23 shows which areas of body were treated, with axilla and groin being the most commonly treated areas. ‘Other’ was mostly reported within abdomen, pubic, legs and jaw areas.

Analgesia options used are reported in Table 24. The open-text responses of ‘other’ indicate that for 138 no analgesia was used, as per the treatment protocol, but the data collection form had not provided a response category of ‘none’. The other category also included open-text entries such as gels, ice, cold sprays and so on, and these adjuncts provide both skin cooling and a degree of analgesia. Skin cooling methods are also reported in Table 24. Ice, cold sprays and other methods were reported. Open-text responses revealed that some were using cooling methods built into the laser machine (e.g. air cooler – Cryo 6, Zimmer MedizinSystems, Irvine, CA, USA). Type of laser used is also presented in Table 24, with alexandrite being the most common laser used. Intense pulsed light (IPL) was used for one-third of treatments, which provides hair removal but is not itself a laser treatment and was not originally intended via the THESEUS study. In one case, as well as receiving hair removal laser treatment, a participant also received pulsed dye laser and CO₂ laser which do not provide targeted hair removal.

Table 25 shows the number of background and lesion pulses reported for each body area treated. Owing to database errors, missing data and not applicable (i.e. body area not treated) data were not always correctly coded and so have been combined.

Deroofing

A total of 41 deroofing procedures were included in the analysis. There were 30 participants included, but some had more than one procedure. Table 26 shows which area of the body was treated, with axilla and groin being the most commonly treated areas.

The preparations for deroofing are described in Table 27.

Figure 7 shows the number of skin tunnels present in the region undergoing treatment mapped next to the number of skin tunnels reported as successfully explored with a blunt probe across procedures.

FIGURE 7.

Number of skin tunnels in regions undergoing treatments.

Table 28 describes what instruments were used for incision and Table 29 describes incision and dissection procedures.

The majority used monopolar diathermy (39/41), but one reported bipolar diathermy (1/41). Wounds were mostly left to heal by secondary intention (40/41), but one reported using sutures. Table 30 describes the type of wound dressings that were used.

Adaptions were reported in six procedures. A description of the adaptions made is described below:

• On two occasions, a disposable diathermy loop was used instead of reusable as this was equipment available at the site. The disposable loop stopped working during procedure, so it was completed with needle tip diathermy.

• On two occasions, reduced diathermy settings for hyfrecation of base was used; the diathermy tip broke during the procedure so the operation was completed with a scalpel.

• On two occasions, a hyfrecator was used rather than diathermy.

The duration of procedures is illustrated in Figure 8 and operator confidence that skin tunnels were fully treated in affected region is reported in Figure 9.

FIGURE 8.

Duration of deroofing procedures.

FIGURE 9.

Confidence that tunnels were fully treated.

Laser recommendations for future trials

1. Pragmatic trials might allow for variation in number of laser treatments, whereas explanatory trials might require tighter instructions than THESEUS to reach recommended number of laser treatments. The cost implications of number of laser treatments should be considered in designing the trial.

2. A more flexible time window (e.g. 4–6 weeks) for next treatment might be more appropriate than ‘within 28 days’ used for THESEUS.

3. Photography presents challenges, is probably not essential and could be left as optional for most future studies.

4. Variation in skin cooling methods was observed and could be left for sites to decide.

5. IPL was used in one-third of treatments (n = 71) in deviation from the protocol because, while it targets the hair follicle, it is a light rather than a laser treatment. There was also variation in laser used, reflecting skin type and laser availability. Future studies of a more pragmatic nature might allow variation in laser/light treatment targeting the hair follicle.

6. Lack of standardisation of number of pulses for background and lesions. Future studies could more prominently emphasise standardisation (which, in THESEUS, was one pulse for background and two pulses for lesions).

Deroofing recommendations for future trials

1. Variation in preparations for surgery that could remain flexible, allowing site and patient preference in future studies.

2. Variation in instrument used and challenges using certain equipment point to future trials being pragmatic and allowing flexibility where possible. More explanatory trials might need tighter standardisation.

3. Variations in procedures to be encouraged in future trials depending on patient need. For example, identification of scarring or lesions of different depths may require clinically different approaches.

4. Secondary intention healing is the standardised approach to wound healing, while future trials could permit variation in wound dressings to permit participant and recruiting site choice.

5. We did not collect data on the type of anaesthetic used in THESEUS as it was assumed that the procedure would be carried out under local anaesthetic, but informal feedback was received that some were undertaken using general anaesthetic. Use of general anaesthetic may reflect procedures that were longer in duration or treatment of multiple lesions exceeding local anaesthetic dose limits. Future trials may wish to be pragmatic in allowing different types of anaesthetics dependent on patient and site preferences. Qualitative data also supports that some patients prefer either local or general anaesthetic. A future trial including deroofing as a rescue therapy for acute flares may wish to restrict to local anaesthetic to avoid the need for an operating theatre setting.

Participant-facing materials

The PPI representatives on the SMG committee reviewed all the participant-facing documentation used in THESEUS. One specific change requested was to add a section covering pregnancy and breastfeeding to the participant information sheet.

Creation of a decision grid covering each of the THESEUS interventions was encouraged by PPI representatives (Table 31). They recommended that the order of the interventions in the first draft of the grid should be changed to follow the order in which they were likely to be used in clinical practice.

Care was taken to minimise participant inconvenience in receiving daily text messages asking for their pain score for 12 weeks, while optimising the response rate. The patient researchers recommended that text messages should be sent at the same time each day to provide routine and that 6 p.m. was the ideal time, to avoid clashing with work and parenting duties. They asked that the window for responses should be extended to 1 a.m. because they were aware that some patients prefer to delay sending a response until a quieter time. The PPI representatives suggested the addition of an ‘opt out’ response for the daily messages, in case they became too onerous for a participant.

A patient with HS kindly contributed to the deroofing video provided to support the introduction of the deroofing procedure (Figure 11). The PPI representatives advised creating two versions, one for patients and one for clinicians, differing only in the technical level of language used for the voice over. Interestingly, the clinician video has received many more views, nearly 1 million, compared with 3600 for the patient video, suggesting that patients mainly saw the video as being intended for clinicians.

FIGURE 11.

Screenshot from deroofing video.

Consensus workshop

Planning for the THESEUS consensus workshop required extensive PPI involvement and Table 32 details the impact of these discussions on the arrangements. In particular, PRPs recommended two additional virtual meetings for patients, run by the PRPs themselves, to prepare for the workshop. The aim was to support and empower patients to contribute to the workshop by provision of a glossary of technical terms, helping them to assimilate the study results and emphasising where their input could make a difference to THESEUS outputs.

Dissemination of THESEUS results

Following discussion with PRPs, it was decided to host a combined for trial participants, clinicians and researchers. The PPI representatives provided input into the presentation to ensure it was accessible to patients and encouraged patient input during the meeting, with several questions being offered by trial participants. Importantly, one of the two preworkshop patient-led virtual meetings took place just prior to the dissemination meeting, to allow the PPI representatives to prepare patients for the technical elements of the meeting, including provision of a glossary of expected terms.

Ensuring continuing communication with trial participants following the dissemination meeting and consensus workshop was an important consideration, particularly because further HS clinical trials are planned building on the foundations from THESEUS. PRPs supported the use of plain language summaries and infographics to summarise the results of THESEUS publications, and these will be created as part of the paper writing process. The HS Trust website is not currently being updated and so the THESEUS study website (currently https://www.cardiff.ac.uk/centre-for-trials-research/research/studies-and-trials/view/theseus) will be maintained indefinitely to provide a platform to disseminate the study outputs.

Reflections from patient advocates in THESEUS team

‘Being part of the THESEUS study has been insightful and empowering. It is refreshing to have been involved from the beginning and not consulted on an end product. The SMG Committee has been welcoming and accommodating of other commitments and made sure the frequency and timing of meetings were enablers.

During discussions the patient view was always encouraged and where there was a difference of opinion, the view of lived experience took precedence. As an example, subjective language used in study materials was adjusted in line with the patient voice because what is acceptable to a clinician may not be understandable to patients or could potentially cause them discomfort. We were mindful that some people in the trial would be new to their diagnosis so choosing our wording for patient information was an important role for the patient advocates to ensure we didn’t exclude potential participants at the initial stages of the study. We were able to translate terminology to make it accessible from a patient community perspective and to show how THESEUS could lay the groundwork to improve future HS care in the UK.

Leading workshops to prepare other PPI representatives ahead of the consensus workshop was a valuable opportunity to build the confidence of those new to patient research and advocacy and also for us to focus on where we feel there are gaps in the demographics of HS PRPs to encourage further participation.

I would like to think our input as patients has meant that access to the study and retention improved. As my first experience on a study of this nature, I have learnt a lot which I know will improve my contributions in future research into HS. From a patient perspective, it gives hope to us as individuals and a community that the research to support people living with HS is steeped in our experience and our hopes for the future.’

Aims and objectives

Pre-meeting scoring – online survey

Prior to the meeting, all potential workshop participants were invited to complete an online survey, providing a starting point for the workshop and allowing those not able to attend to contribute to the prioritisation process. The survey involved selecting ‘your top three’ from the predefined list of HS trials. The online survey was delivered via Microsoft Forms (Microsoft Corporation, Redmond, WA, USA) and simple descriptive statistics were produced detailing the number of times each trial had been selected as a ‘top three trial’.

Workshop small group discussion, ranking and plenary discussion

At the beginning of the workshop, the in-person and online delegates received a presentation summarising the results of the pre-meeting survey, as well as the main THESEUS results relating to participant willingness to receive treatment and eligibility. Participants were then split into break-out groups to discuss the trials and identify their preferred trials.

Groups included at least one clinician, one researcher and two people with lived experience of HS. One break-out group included only participants who were participating remotely. Each group was facilitated by two members of the THESEUS team, who acted as impartial facilitators of the discussion.

In the break-out groups, participants were invited in a round-robin fashion to identify their preferred trials and to explain their choice. Discussion within the groups subsequently considered popular trials and the reasons for their popularity. The subsequent plenary session considered which trials were favoured by different stakeholder groups, such as people with HS or clinicians; in these cases, discussion sought to demonstrate why a trial might be more important to a particular stakeholder. The break-out groups were then asked to agree a small number of preferred trials and at the next plenary session the preferences were compared to identify similarities and differences between the groups’ choices and the underlying reasons. At this point, any trial not prioritised was rejected to streamline continuing discussions.

Impact assessment of prioritised trials – small group discussion, plenary and online voting

Break-out groups were asked to reflect upon the short-list of preferred trials – considering which might have the greatest impact, change clinical practice or make most difference to people living with HS. Following discussion, each group was asked to rank the trials according to these criteria. Rankings were shared during a subsequent plenary session. Following these discussions participants were asked to vote anonymously via an online platform for the two trials which they considered should be prioritised above others. The votes were collated and the final top-three list of priority HS trials was established.

Participants

Twenty-three participants completed the online, preworkshop survey; Table 33 presents the demographics of this sample.

A total of 30 individuals participated in the workshop, including 7 HCPs, 10 researchers and 13 people living with HS. Fourteen of these joined online via the Zoom platform [(Zoom Video Communications, San Jose, CA, USA), including seven people with HS]; some of those who joined online were not present for the entire meeting, joining for the morning or afternoon session.

Pre-meeting online survey

Participants were allowed to select up to three trials and, in total, 68 selections were made, with one participant making only 2 selections. Every trial option was selected at least once. The most frequent selections were laser (hair removal) compared with clindamycin and rifampicin, early intervention with treatment usually used later in care pathway (e.g. biologicals) compared with doxycycline, and clindamycin and rifampicin plus laser (hair removal) compared with clindamycin and rifampicin alone (Figure 13).

FIGURE 13.

Pre-meeting online surveys responses. B: higher dose of standard medical treatment (e.g. doxycycline, clindamycin and rifampicin or other tablet treatment) compared with standard/lower dose; D: clindamycin and rifampicin + laser (hair removal) compared with clindamycin and rifampicin alone; F: early intervention with treatment usually used later in care pathway (e.g. biologicals) compared with doxycycline; J: adalimumab (or biosimilar) compared with clindamycin and rifampicin; K: adalimumab (or biosimilar) + laser (hair removal) compared with adalimumab (or biosimilar) alone; L: adalimumab (or biosimilar) + deroofing of skin tunnels compared with adalimumab (or biosimilar) alone.

Preferred trials

Small group discussion identified factors that participants felt to be important in prioritising future HS research. Discussion often focused upon the perspective of people living with HS, including the availability of treatments in a geographical region, as well as the person’s lived experience of a particular treatment. Interventions not previously available were often judged to be more appealing and more important to include in future HS trials.

There was consensus that future HS research should be available to a broad spectrum of people living with HS, irrespective of their disease stage or geographical location. Early intervention to prevent disease progression was emphasised. People with lived experience of HS supported the element of choice that was available in THESEUS, making study participation more attractive.

Biologicals were regarded positively for inclusion in future research, although people with lived experience of HS were aware that these drugs may be viewed with caution and considered a treatment of last resort. These impressions would need to be negotiated to ensure the acceptability of any future research which includes biologicals.

Table 34 presents the small group ranking of the trial options, with laser, deroofing and biological treatments favoured. As part of the ranking process, the small groups also suggested merging some trial options to broaden their reach and inclusivity and offered new trials based upon the treatment options under consideration. Group 1 suggested merging options K (adalimumab or biosimilar + laser hair removal compared with adalimumab or biosimilar alone) and L (adalimumab or biosimilar + deroofing of skin tunnels compared with adalimumab or biosimilar alone); they also proposed a new laser treatment-focused trial (laser + clindamycin and rifampicin vs. laser alone). Group 2 proposed two additional deroofing trials and group 3 suggested one additional deroofing trial.

Review of the small group rankings led to further discussion and refinement of the trial options during a plenary session. Options C (laser vs. clindamycin and rifampicin) and D (clindamycin and rifampicin + laser vs. clindamycin and rifampicin alone) were combined to form a new option (option M – clindamycin and rifampicin + laser vs. laser alone). Option F (early intervention usually used later in treatment care pathway) was considered an overarching principle that could be incorporated into any of the trial designs and was excluded from further consideration as an intervention itself. Table 35 shows the status of all trial options considered and highlights those taken forward for further consideration and scoring.

Prioritised trials

Small group ranking of the remaining trials demonstrated a growing consensus for trials including laser as a combination treatment. Table 36 shows the small group ranking of the preferred trials and the newly proposed comparisons that address uncertainties about laser treatment in HS.

To close the workshop, 28 participants completed the online voting, including 13 people with HS, 8 researchers and 7 HCPs. Of the 50 responses, 2 participants selected prioritised trials and 6 selected a single prioritised trial. The top three options from the voting were: option K with 25 votes (50% of the votes cast), option M with 16 votes (32%) and option E with 8 votes (16%; Figure 14). Nearly all participants across the stakeholder groups included option K in their selection; 75% of votes for option E (6/8) were from individuals living with HS. Figure 15 presents a consensus prioritised top three for future HS trials.

FIGURE 14.

Consensus vote responses.

FIGURE 15.

Prioritised trials for future HS research.

Implications for health care

By offering medical and non-medical interventions, THESEUS was intended to encourage a MDT approach which is recommended to optimise HS care11 and this has been achieved by centres participating in the study. Integration of medical and non-medical therapy was possible for both dermatology-led and plastic surgery-led recruitment centres.

The training and equipment provided by THESEUS has led to establishment of deroofing as a surgical treatment option in the UK, bringing HS care in the UK in line with other countries. Interest in deroofing is demonstrated by more than 1 million views of the THESEUS deroofing video and by deroofing being the second highest choice in THESEUS in terms of eligibility and participant willingness to receive treatment. While laser and light hair removal treatment was already available in the UK, it was almost never used for HS therapy and THESEUS has shown it can be provided as a treatment option within existing healthcare infrastructure.

Use of HiSTORIC-developed and other recognised OMIs for HS within THESEUS has familiarised 10 centres in the UK with well-validated tools to measure HS severity and monitor patient progress. Several of the OMIs are suitable for routine clinical care, for example HiSQOL can be given to patients to complete in the waiting area before their appointment.

Implications for research

The design of THESEUS was intended to provide the foundations for future HS RCTs. The ten THESEUS sites were spread across the UK and are well placed to be recruiting centres in future HS trials. The sites are familiar with HS OMIs and have established laser and deroofing interventions for HS, should these be taken forward in a future RCT.

The qualitative study nested within THESEUS provided multiple insights to incorporate into future trials (see Chapter 5). A RCT with an active comparator will need to ensure equipoise for participants and clinicians and provide equivalent information, for example study videos, for each intervention. Flexibility should be offered where possible in terms of face-to-face or remote appointments and participant concerns regarding security of image transfer and storage indicates it may be better to avoid clinical photographs as part of virtual trial reviews. The number of OMIs should be minimised and an explanation provided regarding their use, particularly in terms of the frequency of study visits and when remote assessments are scheduled to finish.

If laser treatment is incorporated into a future trial, a decision will be required whether to allow IPL within the treatment arm as a non-laser therapy also targeting the hair follicle. The decision will depend on availability of Nd-YAG and alexandrite lasers at potential recruitment sites and whether the study is located towards the explanatory or pragmatic ends of the RCT spectrum. Some flexibility is probably permissible in terms of the timing of laser treatments 4 to 6 weeks apart; however, the number of pulses for lesions and background skin should be mandated and carefully reinforced. If deroofing is taken forward in a RCT, variation in cutting method could be permitted; however, it may be necessary to specify local anaesthetic only, particularly if deroofing is intended in an acute setting.

The THESEUS consensus workshop has identified a set of RCT designs to prioritise, several of which include combination therapy, building on the 2021 Safety and Efficacy of Adalimumab for Hidradenitis Suppurativa Peri-Surgically study publication comparing wide excision surgery and adalimumab to wide excision surgery alone. 66 In particular, the combination of laser treatment and medical therapy could be compared with laser treatment, or medical therapy, potentially in a multiarm study. Deroofing was also prioritised for future trials, and this could be compared with narrow margin excision, either for chronic lesions or in the setting of treatment of acute flares for which the evidence base is very limited.