Interleukin‐17 inhibitors for the management of severe rosacea

Rosacea is a chronic inflammatory skin condition with unknown aetiology.1 Symptoms of rosacea include facial erythema, telangiectatic vessel formation, eruption of inflammatory papules and pustules, hypertrophy of sebaceous glands of the nose with fibrosis, as well as ocular changes such as blepharitis and conjunctivitis.1 The disease is classified into four subtypes: papulopustular, erythematotelangiectatic, phymatous and ocular.2 Rosacea involves dysregulation in the immune, vascular and nervous systems, as well as skin barrier function impairment.3 Rosacea has a significant impact on the patients' psychological, social and occupational status. There are several treatment options available for symptom control, such as topical metronidazole, ivermectin, azelaic acid and low-dose oral antibiotics and retinoids.1 Challenges linked to treating rosacea include the risk of relapse after treatment discontinuation and a limited range of options for severe and treatment-resistant cases. Here, we report two cases of severe rosacea managed with interleukin 17 (IL-17) inhibitors. A 72-year-old female presented with psoriasis and severe papulopustular rosacea and subsequently commenced on brodalumab as part of a clinical trial (Amgen 20,090,062 and Amgen extension study 20,090,403) for treatment of moderate-to-severe plaque psoriasis from 2010 to 2015 (Figure 1). At three-month review, there was marked improvement in her psoriasis, and incidentally, her rosacea had cleared. As brodalumab was not available in Australia, she briefly commenced secukinumab 300 mg SC weekly injections for 4 weeks as part of a patient familiarisation program in 2015. Unfortunately, she was not eligible for PBS-subsidised treatment with secukinumab. She, therefore, was managing her rosacea with only topical ivermectin with intermittent flares from Dec 2015 to May 2018. In April 2018, she restarted secukinumab 150 mg SC weekly loading dose then every 4 weeks as compassionate supply for her psoriasis. At her one-month review, her psoriasis responded but her rosacea initially flared. This was treated with adjunctive therapy with oral ivermectin single dose and topical permethrin daily. At three-month follow-up, her rosacea responded well and remained clear with an ongoing reduced dose of secukinumab of 150 mg every 4 weeks and topical permethrin for 6 months. Unfortunately, the patient was lost to follow-up after the compassionate supply finished. A 42-year-old female presented with long-term severe erythematotelangiectatic rosacea including facial erythema and swelling. Multiple topical and oral treatments were trialled with limited success including oral isotretinoin, oral doxycycline, ivermectin cream and tacrolimus cream. Her symptoms of burning and flushing were affecting her quality of life. Based on our previous case, she was commenced on a compassionate supply of secukinumab 300 mg SC weekly injections for 4 weeks as a loading dose then 300 mg SC every 4 weeks in November 2021. The patient had marked improvement in her symptoms with only occasional flushing after 12 weeks of treatment (Figure 2). She remained on reduced dose of secukinumab 300 mg SC every 5 weeks with good control of her rosacea. Recent literature has suggested that IL-17 plays a crucial role in the pathogenesis of rosacea.3, 4 Furthermore, it has been hypothesised that IL-17 inhibitors could effectively treat severe cases of rosacea that are resistant to standard treatments. A recent small study, assessing the efficacy of secukinumab in moderate-to-severe papulopustular rosacea in 20 patients, has shown that secukinumab could potentially have activity in rosacea.5 In case 1, there was an initial worsening of rosacea after reinitiating anti-IL-17 therapy. It was thought the immunosuppressive effect of secukinumab may have allowed an increase in the microbial burden over the face. This flare was treated with ivermectin single dose and topical permethrin daily for 6 months which likely also helped in her ongoing remission. It is worth noting that the patient in case 1 achieved better control of rosacea with brodalumab, which is an IL-17A-F inhibitor, unlike secukinumab, which is an IL-17A inhibitor. These two case reports contribute to the growing evidence that IL-17 inhibitors could play a role in managing rosacea. We advocate for larger randomised controlled trials to confirm these findings. The authors have nothing to report. DFM is an investigator and advisory board member for Principia-biopharma and was a primary investigator and/or advisor for Roche, GSK/Novartis and Lilly. SS has no conflicts of interest to declare. The first patient discussed in this manuscript did not provide recent consent to the publication of their medical photographs. The second patient discussed in this manuscript have given written informed consent to the publication of their medical photographs. The data that support the findings of this study are available from the corresponding author upon reasonable request.