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.