Treatment of chronic prurigo with upadacitinib: A case series

Abstract

Chronic prurigo (CPG) is a neuroinflammatory dermatosis characterized by persistent pruritus lasting for at least 6 weeks, along with a history and/or signs of scratching and pruritic skin lesions (papular, nodular, plaque, umbilicated and/or linear).1 It can severely impact the quality of life (QoL) of patients and constitutes a therapeutic challenge.2 Rapid itch control is crucial in managing CPG, as the itch-scratch cycle plays a significant role in perpetuating the condition.1-3 Emerging therapies targeting neuroinflammatory molecules, including Janus Kinase (JAK) inhibitors, are under investigation for their potential in CPG treatment.2 We present three patients with refractory CPG who received treatment with upadacitinib, a selective JAK-1 inhibitor approved in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD). The patients' epidemiological features, clinical presentation, treatment response and quality of life were assessed (Table 1). Treatment response was determined by clinical examination and the peak pruritus numeric rating scale (NRS). Quality of life was assessed using the dermatology life quality index (DLQI). Blood testsa: normal Bx: not performed PP-NRS: 9 DLQI: 25 Topical and intralesional CS Pregabalin (150 mg/day) Methotrexate (SC, 10 mg/week) Dose: 15 mg/day Duration: 7 monthsb CR pruritus (PP-NRS = 0): 1 week NRS improvement ≥4 points: 3 days CR cutaneous lesions: 1 month Blood testsa: IgE 311 UI/mL Bx: compatible with CPG nodular-type Patch-test: positive for Balsam of Peru, Mixed fragrances, Methyldibromoglutaronitrile PP-NRS: 8 DLQI: 22 Topical CS Antihistamines Methotrexate (SC, 15 mg/week) Cyclosporine (3.5 mg/kg/day) Dose: 15 mg/day Duration: 5 monthsb CR pruritus (PP-NRS = 0): 1 week NRS improvement ≥4 points: 2 days CR cutaneous lesions: 1 month Blood testsa: normal Bx: chronic spongiotic dermatitis Patch-test: positive for caine MIX, Fragrance mix PP-NRS: 9 DLQI: 24 Topical and systemic CS Antihistamines Cyclosporine (3 mg/kg/day) Dose: 15 mg/day Duration: 7 monthsb CR pruritus (PP-NRS = 0): 1 week NRS improvement ≥4 points: 4 days CR cutaneous lesions: 2 months Two patients presented with papular and nodular-type CPG, while one patient had plaque-type CPG (Figure 1). The patients experienced intense pruritus and sleep disturbances, greatly impacting their QoL. Prior to upadacitinib treatment, all patients had undergone various therapies, including topical and intralesional corticosteroids, gabapentinoids and conventional immunosuppressants (methotrexate and cyclosporine). All patients had either side effects due to these medications, only mild improvement of pruritus and/or no resolution of cutaneous lesions. After assessing different treatment options, upadacitinib at a daily oral dose of 15 mg was initiated. All three patients reported rapid itch improvement within 3–7 days, with complete resolution of pruritus after 2 weeks of upadacitinib treatment. Cutaneous lesions gradually remitted, leaving residual hyper/hypopigmentation, within 3–4 weeks (Figure 1). No relapses nor adverse events were observed during the follow-up period (median, 6 months), and all patients continued to receive upadacitinib treatment. Chronic prurigo presents a therapeutic challenge, and various off-label therapies such as topical corticosteroids, calcineurin inhibitors, capsaicin, phototherapy, antihistamines, neuromodulators (serlopitant, naltrexone, antidepressants, gabapentinoids), immunomodulators (thalidomide) and immunosuppressants (corticosteroids, methotrexate, cyclosporine), among others2-4 have been used with variable outcomes. Dupilumab is currently the only targeted medication approved to treat CPG in Europe and the United States. Other therapies including IL-31 inhibitors (nemolizumab), JAK inhibitors (abrocitinib and INCB054707), neurokinin 1 receptor inhibitors (serlopitant), mu and kappa opioid receptor modulators (nalbuphine)5 as well as oncostatin-M beta receptor antagonists (vixarelimab) are being evaluated in clinical trials.2, 4 Although the pathogenesis of CPG remains to be fully elucidated, neural dysregulation and inflammatory pathways play a central role.1, 2, 6 Pruritus in CPG, transmitted via cutaneous dermal nerve fibres (C- and Aδ fibres), depends mainly on a non-histaminergic pathway with substance P, oncostatin-M and interleukin (IL)-4, IL-13 and IL-31 acting as main regulators.1, 2, 4, 6 Specifically, IL-31 binds to its receptor on keratinocytes, nerves and eosinophils leading to the activation of JAK 1, JAK 2 and STAT 3 which increases pruritus and perpetuates the inflammatory cascade.2-4 Hence, JAK inhibitors could be effective in downregulating the itch-scratch cycle and leading to disease control. The use of tofacitinib, upadacitinib, baricitinib and abrocitinib in CPG nodular-type has shown good results in isolated case reports.7-10 Our real-life experience with upadacitinib treatment in three patients with refractory CPG illustrates a rapid response in terms of pruritus relief, resolution of skin lesions and improvement in quality of life. Although further evaluation through larger studies is needed, upadacitinib could represent a rapid and well-tolerated alternative treatment for CPG. The authors involved have reported no relevant financial relationships with commercial interest(s). Dr. Riquelme has received honoraria for participation in advisory boards for Sanofi, Abbvie and Leo Pharma. In addition, received support for attending meetings from Sanofi, Abbvie and Lilly. Dr. Gil, Dr. Morgado have no conflicts of interest to declare. The patients in this manuscript have given written informed consent to the publication of their case details. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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