Case report: Baricitinib combined with adjuvant therapy for treatment of atopic dermatitis in a child

Abstract

Dear Editor, Atopic dermatitis (AD) is characterized by skin dryness, recurrent eczematous skin eruptions and intense skin itching. It might affect patients sleep quality and daily activities, making them anxious, depressed and unfocused. Topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs) are the first-line medical therapy for AD. Systemic corticosteroids and immunosuppressants have been used for the management of moderate-to-severe AD. In recent years, targeted biological therapies, which are thought to be safer than systemic immunosuppressants, have been investigated in the treatment of AD. Baricitinib is a Janus kinase (JAK) 1 and JAK2 antagonist approved by the Food and Drug Administration to manage adult patients with moderately to severely active rheumatoid arthritis. Targeting JAK1 and JAK2, baricitinib is considered to be potent in controlling AD by acting on the JAK/signal transducers and activators of transcription signaling pathway. By searching https://clinicaltrials. gov, we found nine clinical trials that investigated the efficiency and safety of baricitinib in treating AD. Three of the trials were completed and demonstrated results. Among them, a phase II clinical trial demonstrated the efficacy of baricitinib used in combination with TCSs to treat moderate-to-severe adult AD. Other two phase III clinical trials have confirmed baricitinib as an effective monotherapy for adults with moderate-to-severe AD, whose skin lesions were not adequately responsive to TCSs. In these trials, the duration of baricitinib usage was 16 weeks, while the dose of 4 mg/d showed the best efficacy, compared with 1 or 2 mg/d. Among these AD patients, the most common adverse drug reactions of baricitinib include headache, nasopharyngitis, infections of upper respiratory tract, herpes simplex infection, abnormal lymphocyte count, abnormal white cell count and elevation of creatinine phosphokinase. Currently, only one ongoing phase III clinical trial aims to evaluate the efficacy of baricitinib in the management of young AD patients aged from 2 to 17 years. However, several clinical studies have demonstrated its safety for longterm use in children suffering from autoinflammatory interferonopathies. In such clinical studies, the dose of baricitinib for treating pediatric patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome or stimulator of interferon genes-associated vasculopathy with onset in infancy was chosen based on estimated glomerular filtration rate (eGFR) and weight of the patients. According to Sanchez et al, the most common side effects during long-term (2.3-5.6 years) usage of baricitinib were treatment-emergent infections. Here, we would like to share a case of childhood refractory severe AD, which responded well to baricitinib. The satisfying improvement of skin lesions in this patient suggested that children with severe refractory AD could benefit from treatment with baricitinib. A 12-year-old boy, with a weight of 32 kg and height of 140 cm, had a history of asthma and severe relapsing AD since several months of age. Several months ago, he suffered from scattered macules and papules all over the body, and he thereby underwent traditional Chinese medicine therapy, which led to exacerbation of skin lesions presented as macules and patches with oozing, blisters, scale and scratchinduced erosions. After that, he was treated topically with emollients, TCSs and TCIs, and orally with cetirizine dihydrochloride oral drops (1 mL, once a day) and chlorphenamine (8 mg, once a day) for 1 month. The worsened skin eruptions were not responsive to the medications mentioned above. His parents then took him to Shenzhen Second People s Hospital. Complete blood count (CBC), erythrocyte sedimentation rate, C-reactive protein, kidney function tests and liver function tests were normal, and tuberculosis testing was negative. His family refused to use systemic immunosuppressants or dupilumab for the management of disease. With informed consent, he was then treated orally with baricitinib (2 mg, once a day) and ebastine (10 mg, every night), and topically with emollients and wet wound dressing of FuFangHuangBo lotion (Shandong Hanfang Pharmaceutical Co.Ltd), which is made from Phellodendron chinense, weeping forsythia and honeysuckle flower (15 minutes three times a day), for 28 days. In this case, we chose 2 mg/d as the initial dose of baricitinib because of the following reasons: First, this dosage was believed to be safe for children with such weight and eGFR. Second, clinical trials have confirmed that both of the baricitinib doses, 2 and 4 mg/d, could significantly improve AD, while the dose of 4 mg/d seemed to be more efficient in the management of AD. Third, the minimal dose of baricitinib available in China is 2 mg, so we prescribed 2 mg/d for this patient. Before the treatment, the Severity Scoring of Atopic Dermatitis (SCORAD) was 96, Eczema Area and Severity Index (EASI) was 70.8, Numerical Rating Scale (NRS) was 10 and Children s Dermatology Life Quality Index (CDLQI) was 28 (Figure 1A-D). After 28 days of treatment, obvious relief of skin lesions and pruritus was shown. SCORAD was 44, EASI was 10.8, NRS was 4 and CDLQI was 12 (Figure 1E-H). In this case, the child was prescribed baricitinib orally for 3 months in total and he did not report any novel discomfort after the beginning of the therapy. CBC, kidney function tests and liver Received: 9 October 2020 Revised: 7 January 2021 Accepted: 21 January 2021