Non‐Glucocorticoid Immunosuppressive Therapy in Post‐Glucocorticoid Persistent or Recurrent Primary Autoimmune Hypophysitis: A Systematic Review

Objective Persistent or recurrent primary autoimmune hypophysitis (PAH) is a rare disease, and the role of non‐glucocorticoid (GC) immunosuppressive therapy (NGIT) such as azathioprine (AZA), mycophenolate mofetil (MMF), rituximab (RTX), methotrexate (MTX), infliximab (IFX), and tacrolimus (TAC) has not been systematically studied. Design A systematic review of post‐GC persistent or recurrent PAH managed with NGIT ( n = 29, including two patients from our centre) was conducted to assess the effectiveness and safety of NGIT in this subset of patients. Results The majority of patients (62.1%) had recurrent disease after an initial response to GC therapy, and the remaining patients had persistent disease (37.9%). Most of the patients (75.8%) received a single NGIT agent (AZA: 14, MMF: 4, RTX: 3, MTX: 1), while the remaining seven patients received multiple NGITs in a sequential manner (AZA→RTX: 4, AZA→MMF→TAC: 1, MMF→IFX: 1, MTX→IFX→RTX: 1). In the majority (59.1%), NGIT was administered concomitantly with GC. The median (IQR) duration of NGIT use was 10.5 (4.0–24.2) months. Overall, clinical, hormonal, and radiological PAH remission was observed in ~91%, ~26%, and ~72%, respectively. Radiological response was best with RTX (100%, 8/8), followed by MMF (~66%, 4/6) and AZA (~37%, 7/19). Overall, adverse events (MMF: alopecia, hepatitis; IFX: pulmonary aspergillosis; AZA: hepatitis, leucopenia) were observed in ~20%. Conclusion NGITs are effective treatment modalities for post‐GC therapy persistent or recurrent PAH. Given the heterogeneity of treatment regimens and limited data, larger studies are needed to determine the optimal agent, timing, and duration of NGIT.