JAK Inhibitors for Autoimmune Hepatitis: One Swallow Does Not Make a Summer

Recently, we reported data on the efficacy and safety of rituximab for patients with autoimmune hepatitis (AIH) [1]. In our cohort, including 35 patients, 14 of whom had failed to achieve a response to previous lines of therapy, 89% reached complete biochemical response after rituximab. This rate was similar (86%) among those with refractory AIH. Although promising, several gaps remain unresolved regarding the use of this anti-CD20 agent for AIH: periodicity and total number of doses, time to evaluate analytical improvement, efficacy and safety on patients with cirrhosis and therapeutic alternative in case of lack of response. In this regard, Gökçe et al. [2] described a case of difficult-to-treat AIH who, after failing several therapies including rituximab, achieved complete biochemical response after 3 months of corticosteroids and tofacitinib, a Janus Kinase (JAK) inhibitor, which was prescribed for cryptogenic organising pneumonia. While JAK inhibitors may represent a promising therapy for refractory AIH due to their ability to modulate inflammatory pathways [3], caution is mandatory when drawing conclusions from isolated case reports. In this respect, we would like to report the case of a 36-year-old woman with a history of a large granular lymphocytic leukaemia and difficult-to-treat enterocolitis, triggered by a previous therapy with alemtuzumab for the leukaemia. While being treated with corticosteroids, she was diagnosed with AIH due to acute hepatitis with positive atypical anti-neutrophil cytoplasmic antibodies and immunoglobulin G (IgG) levels of 2900 mg/dL (normality range 650–1600) plus typical findings at liver biopsy. Besides increasing the dose of prednisone, a second immunosuppressant was added. However, she presented poor tolerance to azathioprine, 6-mercaptopurine, mycophenolate, tacrolimus and cyclosporine. Since she also required therapy for enterocolitis, upadacitinib (45 mg daily), a selective JAK1 inhibitor used for refractory Crohn's disease [4], was initiated. This treatment led to clinical remission of the enterocolitis, but the persistence of increased transaminases and IgG values despite prednisone at a dose of 30 mg/day. For this reason, at the time being, the patient is awaiting the beginning of therapy with rituximab. The case by Gökçe et al. highlights the great need for multicentre and international cohorts for rare diseases such as AIH, especially in case of refractory response, in order to achieve robust and significant data to improve the therapeutic options for patients with AIH. Mar Riveiro-Barciela had full access to all the data in the study and took responsibility for the integrity and accuracy of the results. Concept and design: Mar Riveiro-Barciela, Juan Carlos Ruiz-Cobo, Lourdes Ruiz-Ortega. Drafting of the manuscript: Juan Carlos Ruiz-Cobo, Lourdes Ruiz-Ortega. Critical revision of the manuscript for important intellectual content: all authors. English writing support was provided by Fidelma Greaves. The authors declare no conflicts of interest. All relevant data are presented in the manuscript.