Baricitinib treatment of severe chronic hand eczema: Two case reports

1. Wei W, Zeng H, Zheng R, et al. Cancer registration in China and its role in cancer prevention and control. Lancet Oncol. 2020;21(7):e342-e349. 2. Huang J, Xu J, Chen Y, et al. Camrelizumab versus investigator’s choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020;21(6):832-842. 3. Zhang B, Qi L, Wang X, et al. Phase II clinical trial using Camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma. Cancer Commun. 2020;40(12):711-720. 4. Huang J, Xu B, Mo H, et al. Safety, activity, and biomarkers of SHR1210, an anti-PD-1 antibody, for patients with advanced esophageal carcinoma. Clin Cancer Res. 2018;24(6):1296-1304. 5. Geisler AN, Phillips GS, Barrios DM, et al. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020;83(5):1255-1268. 6. Pereira FA, Mudgil AV, Rosmarin DM. Toxic epidermal necrolysis. J Am Acad Dermatol. 2007;56(2):181-200.

Janus Kinase (JAK) inhibitors target the JAK and signal transducer and activator of transcription (STAT) signaling pathway that modulates T helper (Th)1, Th2, Th17, and Th22 signaling and is involved in many immune-mediated diseases. Baricitinib, an oral selective JAK-1, and -2 inhibitor, has recently been approved for adults with moderate-to-severe atopic dermatitis (AD). 1 The effect of baricitinib on chronic hand eczema (CHE) has not yet been described.
Here we present two cases of CHE successfully treated with baricitinib.

Case 1
A 52-year-old man, who works as a builder, was diagnosed with severe hyperkeratotic CHE for 6 years. He has a history of asthma in childhood (not classified), allergic rhino-conjunctivitis, and no history of AD. Routine patch testing was performed and the results were negative. His CHE did not improve, despite avoidance of work-related irritants. Treatment history included ultra-potent topical corticosteroids, alitretinoin, acitretin, cyclosporine, apremilast (all discontinued due to inefficacy), and methotrexate (discontinued due to side effects).

Case 2
A 55-year-old woman, who works as an administrator, had severe AD with concomitant severe atopic CHE for 5 years. She has a history of allergic asthma, allergic rhino-conjunctivitis, food allergies, and keratoconjunctivitis. She had no relevant exposure to irritants, and there were no contact allergies with clinical relevance to the hands. Treatment history included ultra-potent topical corticosteroids, topical calcineurin inhibitors, prednisolone, methotrexate, cyclosporine, omalizumab (all discontinued due to inefficacy), and dupilumab (discontinued due to side effects).
Both patients were treated with baricitinib (4 mg tablet once per day), because Case 1 had severe refractory CHE and Case 2 had AD with concomitant severe CHE, that had great impact on their quality of life.
Case 1 presented at baseline with 'severe' CHE according to the photographic guide 2 and a hand eczema severity index (HECSI) 3 score of 55 (severe 4 ). After 16 weeks of treatment, the CHE was improved to "almost clear" and the HECSI score to 4 ( Figure 1). The patient's quality of life improved from "strongly impaired" to "not at all impaired" based on the Quality of Life in Hand Eczema Questionnaire (QOLHEQ). 5 Emollients were continued during bariticinib treatment.
Baricitinib was well-tolerated as no side effects occurred.
Case 2 presented at baseline with "severe" CHE and a HECSI score of 47 (severe 4 ). Baricitinib dosage was tapered to 2 mg per day at 12 weeks on request of the patient due to the good effect. After 16 weeks of treatment, the CHE was improved to "almost clear" and the HECSI score to 8 (see Figure 1). Her quality of life improved from "moderately impaired" to "not at all impaired" based on the QOLHEQ. Her AD was improved from "severe" to 'moderate' at 16 weeks of treatment based on a 5-point Investigator Global Assessment scale for AD. 6 Emollients were continued, and a potent topical corticosteroid was used to a limited extent although Th1, Th2, Th17, and Th22 signaling seem to play a role. The JAK-STAT signaling pathway is involved in the signaling of several cytokines that have been shown to play a role in the pathophysiology of atopic CHE, such as interleukin (IL) 4, IL-13, IL-22 and IL-31, 7,8 and hyperkeratotic CHE, such as IL-1, IL-17, and interferon-gamma. 8 Considering that JAK-inhibitors target several cytokine pathways instead of one single pathway, we hypothesized that this could be an effective therapy for the majority of CHE patients. 1,7 Our hypothesis was strengthened by previous literature on three different JAK-inhibitors that showed promising efficacy on CHE. Recently, two phase 3 trials with upadacitinib, an oral JAK-1 inhibitor, presented significant improvements in mild-to-severe CHE in patients with moderateto-severe AD compared to placebo at 16 weeks. 9 A phase 2b trial with gusacitinib, an oral dual pan-JAK/spleen tyrosine kinase (SYK)inhibitor, reported dose-dependent improvements of moderate-tosevere CHE up to 16 weeks compared to placebo. 10 Further, a phase 2a trial with delgocitinib ointment 30 mg/g, a topical pan-JAK inhibitor, showed significant improvements in mild-to-severe CHE compared to placebo at 8 weeks. 11 The subsequent phase 2b trial with delgocitinib cream presented a significant dose-response relationship in efficacy compared to placebo in mild-to-severe CHE at 16 weeks. The ongoing phase 3 trial investigates the efficacy and safety of delgocitinib cream (20 mg/g) up to 16 weeks. 12 In the near future, patients with moderate-to-severe refractory CHE, regardless of subtype, may benefit from treatment with JAK-inhibitors. Further research is necessary to investigate the efficacy and safety profile on a larger scale.