FINAL Management options for people with moderate to severe acne vulgaris - network meta-analyses Research recommendations for review question: For people with moderate to severe acne vulgaris what are the most effective treatment options? Research question - reduced dose oral isotretinoin What is the efficacy of reduced dose oral isotretinoin in the management of acne vulgaris? Why this is important Oral isotretinoin is prescribed by consultant dermatologist-led team for severe forms of acne resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy. The daily dose typically ranges between 0.5mg to 1mg/kg, however dosage adjustments may be required for people with severe intolerances or whom are at higher risk of developing serious adverse effects. There is limited high-quality data on the efficacy and optimum treatment duration of reduced (less than 0.5mg/kg) daily dose isotretinoin in acne. Furthermore, there have been reports of the successful use of reduced daily dose isotretinoin, including weekly (mini) or bi-weekly (micro) dosage regime as maintenance therapy in people with recurrent relapse despite adequate response to multiple courses of isotretinoin. The evidence for reduced dose isotretinoin as maintenance therapy have been limited to case series and small cohort studies. Further research will help to establish if • reduced daily dose of oral isotretinoin is effective in the treatment of acne vulgaris • reduced dose isotretinoin regime is effective as maintenance therapy; and • the optimum duration of treatment. Table 26: Research recommendation rationale Research question What is the efficacy of reduced dose oral isotretinoin in the management of acne vulgaris? Why is this needed Importance to ‘patients’ or the The daily dose of isotretinoin prescribed usually ranges between population 0.5mg – 1mg/kg. For some people, the dosage adjustment to the maximum tolerated dose may reduce the risk of adverse effects, as the risk of certain adverse effects is dose dependent. However, there is limited high-quality data on the effectiveness of reduced daily dose of isotretinoin for treating acne and the optimum duration of treatment. In people with recurrent acne relapse despite adequate response to multiple courses of isotretinoin, reduced dose isotretinoin regime may be an attractive option. However, evidence for reduced dose isotretinoin in this population is limited to case series and small cohort studies. Relevance to NICE guidance There was limited evidence for the use of oral isotretinoin at a reduced daily dose in acne for the committee to make a strong recommendation. There was a lack of data on the use of low dose isotretinoin in acne maintenance therapy for any recommendations to be made. Therefore, research investigating the efficacy and safety of reduced dose oral isotretinoin is warranted. 394 Acne vulgaris: evidence reviews for management options for people with moderate to severe acne vulgaris (NMA) FINAL(June 2021) FINAL Management options for people with moderate to severe acne vulgaris - network meta-analyses Research question What is the efficacy of reduced dose oral isotretinoin in the management of acne vulgaris? Relevance to the NHS Acne vulgaris, which is the eighth most prevalent disease globally, affects the majority of teenagers and young adults and is common in the UK. Severe intolerance, significant adverse effects are dose dependent and therefore reduced dose oral isotretinoin may offer a safer and effective alternative to standard dose oral isotretinoin. For people with recurrent relapsing acne, treatment options are currently limited and reduced daily dose including mini and micro dose regimes may be a suitable and effective option as maintenance treatment. National priorities • The Medicines and Healthcare Products Regulatory Agency (MHRA) in 2020 are in the process of conducting an in-depth review of psychiatric and sexual adverse effects of oral isotretinoin with the aim to reduce risk of these adverse effects. As many isotretinoin associated adverse effects are dose related, there is a clear benefit of investigating whether reduced dose oral isotretinoin is safe and effective. • Reducing antibiotic prescribing in order to prevent antimicrobial resistance is a national priority. It would be helpful to determine whether reduced dose oral isotretinoin would be an effective and safe alternative to repeated courses of oral and/or topical antibiotics in the treatment of acne and as maintenance therapy. Current evidence base Limited research has been conducted on this area and therefore additional, high-quality studies are required. Equality Not applicable Feasibility People receiving oral isotretinoin would need to be provided with adequate detailed information about the potential adverse effects of isotretinoin and participants in studies investigating reduced dose oral isotretinoin would need to be monitored for these adverse effects. Other comments Not applicable Table 27: Research recommendation characteristics table Criterion Explanation Population People with: • severe forms of acne resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy • refractory acne vulgaris despite previous treatment courses with standard daily dose oral isotretinoin • cleared acne who require maintenance treatment due to previous relapses. Intervention Reduced dose oral isotretinoin as: • reduced daily dose (less than 0.5mg/kg) • reduced dose regime (mini or micro) Comparator • Standard daily dose of isotretinoin • Treatment that includes an oral antibiotic 394 Acne vulgaris: evidence reviews for management options for people with moderate to severe acne vulgaris (NMA) FINAL(June 2021) FINAL Management options for people with moderate to severe acne vulgaris - network meta-analyses Criterion Explanation Outcomes • Clinician reported improvement, including change in acne lesion count • Patient reported improvement • Recurrence • Adverse events, in particular: - mucosal / cutaneous changes (for example new chelitis) - change in mood - new psychiatric diagnosis - suicidality Study design Randomised controlled trial Timeframe • 6 months (intervention) and 12 months (follow-up) for treatment study • 12 months (intervention) and 12 months (follow-up) for maintenance study Additional information Not applicable Research question - physical modalities (excluding chemical peels) What is the effectiveness of physical modalities, (such as light devices) in the treatment of acne vulgaris orpersistent acne vulgaris-related scarring? Why this is important Physical treatments for acne are popular with people because 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. They are currently available in the private sector but there is no standardisation of treatment modalities or duration. Many different physical therapies have been described for acne including: • Comedone extraction • Phototherapy – including UVB, intense pulsed light, blue and red light • Photochemical therapy (e.g. photodynamic therapy) • Laser • Photopneumatic therapy (e.g. intense pulsed light + vacuum) • Photothermal therapy (eg gold nanoparticles +light or laser) Physical treatments are also used for acne scarring. These include: • Punch excision • CO2 laser • Dermabrasion • Radiofrequency (e.g. fractional microneedling, bipolar) Further research is required to determine the most effective physical treatments for acne and acne scarring. This could open the way to wider availability in the NHS. Table 28: 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 394 Acne vulgaris: evidence reviews for management options for people with moderate to severe acne vulgaris (NMA) FINAL(June 2021) FINAL Management options for people with moderate to severe acne vulgaris - network meta-analyses 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? 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. Relevance to the NHS Acne vulgaris is the most common skin 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