1

2 Research recommendations for review question: For people with mild to 3 moderate vulgaris what are the most effective treatment options?

4 Research question - physical modalities 5 What is the effectiveness of physical modalities (such as light devices) in the treatment of 6 acne vulgaris or persistent acne vulgaris-related scarring?

7 Why this is important 8 Physical treatments for acne are popular with people because they have the benefit of 9 treating a local area without systemic effects. They can be used in people with co-morbidities 10 or side effects where other treatments are unsuitable. They are currently available in the 11 private sector but there is no standardisation of treatment modalities or duration. Many 12 different physical therapies have been described for acne including: 13 • Comedone extraction 14 • Phototherapy – including UVB, intense pulsed light, blue and red light 15 • Photochemical therapy (e.g. photodynamic therapy) 16 • Laser 17 • Photopneumatic therapy (e.g. intense pulsed light + vacuum) 18 • Photothermal therapy (eg gold nanoparticles +light or laser) 19 Physical treatments are also used for acne scarring. These include: 20 • Punch excision 21 • CO2 laser 22 • Dermabrasion 23 • Radiofrequency (e.g. fractional microneedling, bipolar) 24 Further research is required to determine the most effective physical treatments for acne and 25 acne scarring. This could open the way to wider availability in the NHS.

26 Table 26: Research recommendation rationale Research question What is the effectiveness of physical modalities (such as light devices) in the treatment of acne vulgaris or persistent acne vulgaris-related scarring? Why is this needed Importance to ‘patients’ or the Physical treatments for acne are popular with people because population they have the benefit of treating a local area without systemic effects. They can be used in people with co-morbidities or side effects where other treatments are unsuitable. There is evidence from small studies that physical therapies including various light sources with or without addition of chemical or physical photosensitiser may be effective in all grades of acne. There is also some evidence to support CO2 laser treatment for acne scarring. However, the studies are too small or of insufficient quality to allow recommendations to be made. Relevance to NICE guidance Currently physical treatments for acne vulgaris cannot be recommended. Weak recommendation can be made for CO2 laser for acne scarring, but stronger evidence is required to allow a stronger recommendation. which would lead to wider availability on NHS.

390 Acne Vulgaris: evidence reviews for management options for people with mild to moderate acne vulgaris (NMA) FINAL (June 2021)

Research question What is the effectiveness of physical modalities (such as light devices) in the treatment of acne vulgaris or persistent acne vulgaris-related scarring? Relevance to the NHS Acne vulgaris is the most common condition affecting the majority of teenagers and young adults. Acne scarring leads to lifelong psychological distress for some people. Physical treatments for acne could provide an alternative for people unwilling or unable to use other treatment modalities. With more evidence of effectiveness and cost effectiveness these treatments may become available on the NHS. Physical treatments for acne scarring may benefit the NHS by reducing psychological morbidity. National priorities There are 2 national priorities, one is to improve young people’s mental health and another is to reduce antibiotic prescribing to prevent resistance. • Improving the mental health of young people is a national priority. Improving acne can have a positive impact on mental health. Rates of depression and suicide are increasing in the under 25-year-old age group, especially amongst men 20-25 years old. (suicides in the UK 2019 ons.gov.uk). In 2018 the government produced a paper ‘Transforming children’s and young people’s mental health provision’, including improving services for those 16-25 years old. This aligns with a need to understand support required for young people with acne vulgaris https://www.gov.uk/government/consultations/transforming- children-and-young-peoples-mental-health-provision-a-green- paper/quick-read-transforming-children-and-young-peoples- mental-health-provision • Acne has traditionally been treated with long courses of antibiotics. If any particular type of physical treatment could be identified as having a positive impact on acne vulgaris then it may lead to a decreased need for antibiotics. Antibiotic resistance is rising in the UK and the government wants to optimise antibiotic prescribing to prevent the development of superbugs. Keeping people well informed would therefore help to address this priority (Tackling antimicrobial resistance 2019–2024 The UK’s five-year national action plan Published 24 January 2019. HM Government) https://assets.publishing.service.gov.uk/government/uploads/s ystem/uploads/attachment_data/file/784894/UK_AMR_5_year _national_action_plan.pdf Current evidence base It is hard to draw conclusions from the current evidence. There are a lack of existing randomised controlled trials in physical treatments for acne and acne scarring, and those which have been done have been variable quality on small numbers of participants. Equality Access to any recommended physical treatments for acne or acne scarring currently differs across the country and according to socioeconomic group. They are mainly available in the private sector. Feasibility Physical treatments need to be supervised, even if they are delivered at home. There would be significant NHS costs associated with setting up provision for physical treatments, but this may be offset by benefits. A time commitment from particpants would be required. Other comments Not applicable

391 Acne Vulgaris: evidence reviews for management options for people with mild to moderate acne vulgaris (NMA) FINAL (June 2021)

1 Table 27: Research recommendation characteristics table - (a) relates to acne 2 management and (b) persistent acne vulgaris-related scarring management Criterion Explanation Population a) Adults with acne vulgaris

b) Adults with persistent acne-related scarring Intervention a) any physical intervention for acne, for example: • Blue light therapy weekly for 3 months

b) any physical intervention for acne scarring, for example • CO2 laser single or multiple treatments Comparison (a) no treatment or another active treatment.

b) no treatment for acne scarring Outcome a) Participant reported improvement, clinician reported improvement in lesion count b) Participant reported improvement, clinician reported improvement in scar appearance a) Recurrence a&b) Side effects: participant and clinician reported, including pigmentary changes and scarring Study design Randomised controlled trial Timeframe a) • 3-6 months (intervention) • 6 month (follow-up) b) • Intervention period • 6 and 12 month follow up Additional information Ideally longer term follow-up data collection would also be useful.

3

4 Research question - chemical peels 5 What is the effectiveness of chemical peels in the treatment of acne vulgaris or persistent 6 acne vulgaris-related scarring?

7 Why this is important 8 Chemical peels are used to remove the surface of the skin. Peels may be ‘superficial’ for 9 treatment of acne vulgaris, removing the dead layer of skin, or ‘deeper’ for atrophic scar 10 management. They are usually applied repeatedly as a course of treatment. Chemical peels 11 are currently not used as standard treatment in the NHS but are available to buy by the 12 public and can be provided by private aesthetic practitioners. The use of chemical peels has 13 potential to change acne and acne scarring management, as an alternative to those who 14 cannot use, tolerate, or are resistant, to other treatments. Therefore, further research is 15 needed to establish its effectiveness.

16 Table 28: Research recommendation rationale Research question What is the effectiveness of chemical peels in the treatment of acne vulgaris or persistent acne vulgaris-related scarring? Why is this needed

392 Acne Vulgaris: evidence reviews for management options for people with mild to moderate acne vulgaris (NMA) FINAL (June 2021)

Research question What is the effectiveness of chemical peels in the treatment of acne vulgaris or persistent acne vulgaris-related scarring? Importance to ‘patients’ or The use of chemical peels has potential to change acne and acne the population scarring management, as an alternative to those who cannot use, tolerate, or are resistant, to other treatments. Therefore further research is required to increase the robustness of the evidence Relevance to NICE guidance Chemical peels are currently not routinely offered as a treatment of acne vulgaris or acne associated scarring in the NHS and there is insufficient evidence to make a strong recommendation. Relevance to the NHS Acne vulgaris is the most common affecting the majority of teenagers and young adults. Acne scarring leads to lifelong psychological distress for some people. Chemical peels for acne could provide an alternative for people unwilling or unable to use other treatment modalities. With more evidence of effectiveness and cost effectiveness these treatments may become available on the NHS. Chemical peels for acne scarring may benefit the NHS by reducing psychological morbidity National priorities • Acne has traditionally been treated with long courses of antibiotics. If chemical peels would be effective in the management of acne vulgaris then it may lead to a decreased need for antibiotics. Antibiotic resistance is rising in the UK and the government wants to optimise antibiotic prescribing to prevent the development of superbugs. Keeping people well informed would therefore help to address this priority (Tackling antimicrobial resistance 2019–2024 The UK’s five-year national action plan Published 24 January 2019. HM Government) https://assets.publishing.service.gov.uk/government/uploads/sy stem/uploads/attachment_data/file/784894/UK_AMR_5_year_n ational_action_plan.pdf • There are safety concerns about the use of oral retinoids (https://www.gov.uk/government/publications/isotretinoin-for- severe-acne-uses-and-effects) so provision of alternative therapy would be welcome if safe and effective. • Improving the mental health of young people is a national priority. If chemical peels are safe and effective to improve acne it may help improve self-esteem and confidence. Rates of depression and suicide are increasing in the under 25-year-old age group, especially amongst men 20-25 years old. (suicides in the UK 2019 ons.gov.uk). In 2018 the government produced a paper ‘Transforming children’s and young people’s mental health provision’, including improving services for those 16-25 years old. More effective acne treatment can have a positive impact on mental wellbeing and therefore addresses this priority. https://www.gov.uk/government/consultations/transforming- children-and-young-peoples-mental-health-provision-a-green- paper/quick-read-transforming-children-and-young-peoples- mental-health-provision Current evidence base There was no evidence for the use of chemical peels, either alone or combined, in moderate to severe acne treatment. There was some evidence that chemical peels may be effective in the treatment of mild to moderate acne. However, there was a low number of studies with small sample size. None of the studies compared effectiveness of chemical peels against placebo. The evidence base for chemical peels in treatment of acne associated scarring was low to very low quality with small sample size and limited follow-up time. Equality None specified

393 Acne Vulgaris: evidence reviews for management options for people with mild to moderate acne vulgaris (NMA) FINAL (June 2021)

Research question What is the effectiveness of chemical peels in the treatment of acne vulgaris or persistent acne vulgaris-related scarring? Feasibility This research is feasible Other comments Not applicable

1 Table 29: Research recommendation characteristics table – (a) relates to acne 2 management and (b) persistent acne vulgaris-related scarring management Criterion Explanation Population a) Adults with acne vulgaris

b) Adults with persistent acne-related scarring Intervention a) Chemical peels for the treatment acne b) Chemical peels for the treatment of acne associated scarring Comparison Any other peel Any other treatment Placebo Outcome a) Participant reported improvement, clinician reported improvement in lesion count b) Participant reported improvement, clinician reported improvement in scar appearance a) Recurrence a&b) Side effects: participant and clinician reported, including pigmentary changes and scarring Study design Randomised controlled parallel or split-face trial Timeframe Likely treatment over 3 months with follow up to 3 years Additional information Not applicable

3

4 Research question – hormone-modifying agents in the treatment of acne

5 What is the effectiveness of hormone modifying agents in the treatment of acne vulgaris?

6 Why this is important 7 Hormone modifying agents are used in the management of acne based on clinical expertise 8 and experience. These treatments may be beneficial for people requiring long-term 9 maintenance or those who do not wish to take oral antibiotics or isotretinoin. There is 10 currently limited evidence of and long-term safety. 11 Hormone modifying agents may include: 12 • Oral 13 • Oral acetate (alone or combined with ethinyl oestradiol) 14 • Oral combined oral contraceptive preparations containing or other anti- 15 androgenic 16 • Oral metformin (indirect antiandrogenic effect) 17 • Topical clascoterone 18 Further research is required to determine the efficacy of hormone modifying agents in the 19 treatment of acne vulgaris.

394 Acne Vulgaris: evidence reviews for management options for people with mild to moderate acne vulgaris (NMA) FINAL (June 2021)

1 Table 30: Research recommendation rationale Research question What is the effectiveness of hormone modifying agents in the treatment of acne vulgaris? Why is this needed Importance to ‘patients’ or the Hormone modifying agents may be an alternative option for population people with acne who do not wish to take or have contraindications to oral antibiotics or isotretinoin. It can be used long-term with minimal monitoring and can form part of the maintenance treatment in acne. There is insufficient evidence from the review to make recommendations though it is used in clinical practice for selective patients. Relevance to NICE guidance Hormone modifying agents are currently not included in the recommendations for acne management. More research and high-quality evidence may lead to widening the recommendation on acne management and help individuals access these treatments as part of their care. Relevance to the NHS Acne vulgaris is the most common skin condition affecting the majority of teenagers and young adults. In some people, acne may persist or develop in adulthood. Hormone modifying agents could provide an alternative option in the treatment of acne, which requires minimal monitoring and may be offered in primary care and for maintenance treatment.

National priorities There are 2 national priorities, one is to improve young people’s mental health, and another is to reduce antibiotic prescribing to prevent resistance. There is also an MHRA review underway regarding isotretinoin prescribing due to concerns about safety. • Improving the mental health of young people is a national priority. Improving acne can have a positive impact on mental health. Rates of depression and suicide are increasing in the under 25-year-old age group, especially amongst men 20-25 years old. (suicides in the UK 2019 ons.gov.uk). In 2018 the government produced a paper ‘Transforming children’s and young people’s mental health provision’, including improving services for those 16-25 years old. This aligns with a need support young people with acne vulgaris, highlighting the importance of timely treatment and its impact on the person’s mental wellbeing. https://www.gov.uk/government/consultations/transforming- children-and-young-peoples-mental-health-provision-a-green- paper/quick-read-transforming-children-and-young-peoples- mental-health-provision • Antibiotic resistance is rising in the UK and the government wants to optimise antibiotic prescribing to prevent the development of multi-drug resistant pathogens. If hormone modifying agents have been shown to be an effective treatment in acne, this will lead to reduction in antibiotic prescribing. (Tackling antimicrobial resistance 2019–2024 The UK’s five-year national action plan Published 24 January 2019. HM Government) https://assets.publishing.service.gov.uk/government/uploads/s ystem/uploads/attachment_data/file/784894/UK_AMR_5_year _national_action_plan.pdf • Hormone modifying agents may be an alternative treatment option for individuals who do not wish to or have contraindications to isotretinoin. This is important as there is currently an ongoing review by the MHRA on the safety of isotretinoin.

395 Acne Vulgaris: evidence reviews for management options for people with mild to moderate acne vulgaris (NMA) FINAL (June 2021)

Research question What is the effectiveness of hormone modifying agents in the treatment of acne vulgaris? Current evidence base There is limited evidence available for the use of hormone modifying agents in the treatment of acne. The trials were small, with differing primary outcomes and were of varying quality. It is hard to draw conclusions from the current evidence. Equality The use of hormone modifying agents in the treatment of acne currently differs across the country and may be more readily available in the private sector. Oral hormone modifying agents which are anti-androgenic are used in females. Topical hormone modifying agents have been shown to be safe in males and children aged 9 and above. Feasibility Hormone modifying agents are low cost, and available in primary care. Minimal monitoring is required for long-term use. Other comments Not applicable

1 Table 31: Research recommendation characteristics table - (a) relates to acne 2 management in adult females and (b) acne management in adult or 3 adolescent Criterion Explanation Population a) Adult females with acne vulgaris b) Adults or adolescents with acne vulgaris

Intervention a) Any oral or topical anti-, for example: • Spironolactone • Oral • Topical clascoterone

b) Any topical anti-androgen, for example • Topical clascoterone

Comparison No treatment or another active treatment.

Outcome • Participant reported improvement, clinician reported improvement in lesion count • Recurrence • Side effects: participant and clinician reported, including pigmentary changes and scarring Study design Randomised controlled trial Timeframe Intervention period • 6 months (intervention) • 6 month (follow-up) Additional information Ideally longer term follow-up data collection would also be useful.

4 5 6 7

396 Acne Vulgaris: evidence reviews for management options for people with mild to moderate acne vulgaris (NMA) FINAL (June 2021)