Real-life experience of abrocitinib for the treatment of female patients with persistent erythema of rosacea

Abstract

Rosacea, a common and chronic skin disorder, presents with various cutaneous manifestations. The phenotype of rosacea determines the approach to treatment. Refractory rosacea with persistent erythema invariably necessitates pharmacologic agents. Herein, we report a case series on three female patients with persistent erythema of rosacea treated by abrocitinib, a JAK-1 inhibitor.

Introduction

Rosacea is a chronic inflammatory cutaneous disease characterized by persistent centrofacial erythema, papules, pustules, telangiectasia, flushing, phymatous changes, burning or stinging sensations, and dryness. Ocular involvement may also occur. The pathogenesis of rosacea is terribly complicated and involves multiple factors, including genetics, innate immune abnormality, inflammatory reactions to cutaneous microorganisms, vascular hyperreactivity, and so on. In 2017, the global ROSacea Consensus (ROSCO) panel proposed a phenotype-based approach to categorize the clinical features of rosacea, ¹ which aligns with the approaches of the National Rosacea Society (NRS) and American Acne. ²

The approach to treating rosacea is determined by its phenotype. However, it is important to note that refractory rosacea with persistent erythema inevitably requires treatment with pharmacologic agents. Topical therapies, including metronidazole, azelaic acid, topical ivermectin, or sulfacetamide-sulfur, are commonly used, and tetracycline-class antibiotics often serve as first-line systemic agents. In addition, laser therapy, intense pulsed light, and photodynamic therapy have also been utilized in this context. Moreover, the Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathways appear to be involved in the occurrence and development of rosacea. Herein, we present three cases of refractory persistent erythema in rosacea patients who responded positively to treatment with abrocitinib, a highly-selective JAK-1 inhibitor.

Cases presentation

These case reports present three female patients with refractory rosacea who received abrocitinib treatment, a highly- selective JAK-1 inhibitor approved to treat moderate-to-severe atopic dermatitis (AD). They had the same clinical phenotypes of persistent erythema. The demographic and clinical information of each patient was recorded, including age, sex, duration of disease, previous treatment, abrocitinib dosage, abrocitinib treatment duration, concomitant medications, and adverse events (Table 1). Diagnosis was established through diagnostic criteria (fixed centrofacial erythema in a characteristic pattern that may periodically intensify), major phenotypes (flushing and telangiectasia), and minor phenotypes (burning or stinging and dry appearance), supported by patients’ history and skin examination findings. All patients complained of intermittent pruritus, pain, burning, or stinging sensations that severely affected their quality of life.

Table 1.

Demographic and clinical data of three rosacea patients treated with abrocitinib (The efficacy of abrocitinib was assessed by the clinician’s Erythema Assessment (CEA), a 5-point grading scale employed by dermatologists to assess the severity of facial erythema. All patients’ CEA scores were between 3 and 4. The clinical photos were retrospectively reviewed using a VISIA skin analysis imaging system at baseline, week 4, and week 12. We considered the treatment to be effective when the facial erythema disappeared or almost disappeared (CEA score 0–1). Additionally, we conducted a patient satisfaction survey. Patient satisfaction was divided into four grades: good, fair, poor, and even worse).

Case	Sex/age, y	Disease duration, y	History of treatments	Dosage	Treatment duration, w	Concomitant medications	CEA score at baseline	CEA score at week 12	Patients satisfaction	Adverse events
1	F/35	10	hydroxychloroquine, carvedilol, intense pulsed light	100 mg qd	16	None	4	0	Good	None
2	F/35	3	Hydroxychloroquine, doxycycline	100 mg qd	16	None	4	1	Good	None
3	F/55	1	hydroxychloroquine, carvedilol, doxycycline, intense pulsed light	100 mg qd	18	None	3	0	Good	None

Prior to initiating treatment with abrocitinib, all patients underwent various therapies, including treatments with laser and intense pulsed light, topical calcineurin inhibitors, oral hydroxychloroquine, carvedilol, and antibiotics. However, the poor therapeutic outcomes led patients to discontinue these treatments. After assessing the different treatment options, abrocitinib was initiated at a daily oral dose of 100 mg. The decision to use abrocitinib was influenced by existing literature supporting its efficacy in treating steroid-induced rosacea and its high selectivity against JAK1. Notably, by week 12, all patients experienced significant regression of facial erythema (Figure 1). Additionally, all patients expressed satisfaction with the treatment outcomes. The abrocitinib dosage was adjusted to 100 mg every other day for 4 weeks, followed by twice a week for 4 weeks. No relapses or adverse events were observed, prompting the discontinuation of abrocitinib therapy.

Figure 1.

The clinical photos were retrospectively reviewed using a VISIA skin analysis imaging system at baseline, week 4, and week 12.

Discussion

Rosacea is a common inflammatory disorder that presents with various clinical manifestations. It is often accompanied by systemic comorbidities that are classified into five categories: neurologic disorders, cardiovascular diseases, gastrointestinal disorders, psychiatric disorders, and others. Notably, the treatment approaches for rosacea vary depending on the specific phenotypes observed. For instance, when persistent facial erythema does not improve sufficiently with general measures and behavioral changes, treatment with lasers, intense pulsed light, or pharmacologic agents may be considered. In the present case reports, we highlight three patients with refractory rosacea characterized by prominent, persistent facial erythema, which remained unresponsive to various treatment modalities.

Abrocitinib, an oral highly selective JAK1 inhibitor, has achieved satisfactory therapeutic effects in the treatment of a group of cutaneous disorders, including alopecia areata, ³ plaque psoriasis, ⁴ lichen sclerosus, ⁵ Hailey-Hailey disease, ⁶ necrobiosis lipodica, ⁷ prurigo nodularis, ⁸ primary cutaneous lichenoid amyloidosis, ⁹ and others. However, reports on the use of JAK inhibitors for treating rosacea have been limited. Sun et al. ¹⁰ conducted a retrospective study evaluating the efficacy and safety of JAK1/3 inhibitors, specifically tofacitinib, in rosacea patients. Their findings suggested that tofacitinib could ameliorate symptoms associated with inflammatory lesions. Similarly, Li et al. ¹¹ presented a case of steroid-induced rosacea that was successfully treated with tofacitinib. More recently, Xu et al. reported on four Chinese patients with steroid-induced rosacea characterized by both persistent erythema and inflammatory papules. These patients were treated with abrocitinib, showing a favorable efficacy and safety profile. ¹²

The TLR2 signaling pathway plays a vital role in the development of steroid-induced rosacea. It is speculated that JAK1 inhibitors suppress inflammatory factors, including IL-6, IL-10, IFN-γ, and other factors associated with steroid-induced rosacea, by inhibiting the JAK/STAT signaling pathway. However, real-life experience with abrocitinib in treating rosacea characterized solely by persistent erythema is limited. In our study, three patients with persistent erythema experienced significant alleviation; their CEA scores decreased by more than 2 points after 12 weeks of treatment with abrocitinib. Abrocitinib therapy also effectively alleviated the anxiety and depression symptoms of the patients, which are among the systemic comorbidities associated with rosacea. Additionally, no adverse events were observed in these cases, further supporting the safety profile of abrocitinib. Notably, Li et al. ¹³ found that rosacea caused by Demodex folliculorum infection may cause the inflammation through activation of the JAK/STAT signaling pathway. Therefore, inhibiting the JAK/STAT signaling pathway might offer a potential therapeutic approach for rosacea. However, this study also addresses the relationship between inflammatory lesions of rosacea. Thus, detailed investigations are required to elucidate the mechanisms by which abrocitinib treats the persistent erythema associated with rosacea.

Conclusion

Our observations in this case reports suggest that abrocitinib could serve as a promising therapeutic option for rosacea with refractory persistent erythema. Further large-scale studies are required to investigate the exact mechanisms and to evaluate the long-term efficacy and safety of abrocitinib in treating this condition.