Effectiveness and Safety of Immunosuppressive Therapy in Recurrent Autoimmune Pancreatitis

Background Autoimmune pancreatitis (AIP) is a distinct type of chronic pancreatitis that responds well to glucocorticoid therapy. However, some patients experience frequent relapses or become glucocorticoid-dependent. In Western countries, immunosuppressive agents such as azathioprine are widely used to maintain remission. In contrast, evidence for the use of immunosuppressive agents for AIP is limited in Japan and other Asian countries. Therefore, this study aimed to evaluate the efficacy and safety of immunosuppressive agents in patients with refractory AIP. Methods We retrospectively analyzed 12 Japanese patients with type 1 AIP who experienced two or more documented relapses and received immunosuppressive therapy. Clinical remission, adverse events, and the incidence of malignancy were assessed. Results Among 199 patients with AIP treated between 2006 and 2024, 12 (6.0%) with multiple relapses were administered immunosuppressive agents, including azathioprine (n=9), tacrolimus (n=2), and methotrexate (n=1). Nine patients continued therapy for at least two months; of these, eight (88.9%) maintained clinical remission without relapse during treatment. One patient relapsed. However, three patients (25.0%) were unable to continue therapy due to adverse events. Two patients developed malignancies during the long-term follow-up: one with malignant lymphoma and the other with small cell lung cancer. Conclusion Immunosuppressive therapy may contribute to the maintenance of remission in some AIP patients with glucocorticoid-dependent or repeated relapses, even among Japanese patients. However, adverse events led to treatment discontinuation in 25% of patients, and two developed malignancies during follow-up. These findings underscore the need for careful patient selection, individualized risk-benefit evaluation, and ongoing monitoring.