Mycophenolate mofetil is superior to azathioprine for the induction of remission in treatment-naive autoimmune hepatitis [CAMARO trial]

Background and aims: In patients with autoimmune hepatitis (AIH) the classical predniso (lo)ne/azathioprine regimen to induce complete remission is recommended in all present guidelines. Cessation of azathioprine is, however, necessary in approximately 15% of patients due to side effects. In uncontrolled studies, mycophenolate mofetil (MMF) has demonstrated a potent effect in achieving complete remission in the majority of patients with AIH, and seems to have less adverse events. The aim of this study was to compare the potential benefits of first‐line MMF over azathioprine, both in combination with predniso (lo)ne, as induction therapy in patients with treatment‐naive AIH. Method: In this 24‐week, prospective, randomised, open‐label, multicentre superiority trial we enrolled 70 patients with AIH. Treatment was started with predniso (lo)ne at 40 or 60 mg daily (depending onweight) and subsequently tapered to a minimum of 5 mg daily according to a dosing scheme. After 4 weeks, patients were randomly allocated (1:1) to either MMF (max. daily dose 2000 mg) or azathioprine (max. daily dose 100 mg). The primary end point was biochemical remission at 24weeks, defined as serum levels of alanine aminotransferase and immunoglobulin G below the upper limit of normal (intention‐to‐treat population). Secondary end points included safety and tolerability of MMF and azathioprine, time to remission, and adverse events. Safety was assessed in all patients having taken at least one dose of the study drug. The trial was registered with ClinicalTrials.gov, #NCT02900443. Results: 70 patients (mean 57.9 years (standard deviation (SD) 14.0); 72.9% female) were randomly assigned to MMF plus prednis (ol)one (n = 39) or azathioprine plus prednis (ol)one (n = 31). The primaryend point was met in 55.3% of patients assigned to MMF and in 25.8% assigned to azathioprine (difference, 29.5 percentage points; 95% confidence interval, 6.1 to 48.5; p = 0.014). Treatment‐related severe adverse events were absent with MMF and occurred in 3 patients in the azathioprine group (9.7%) (p = 0.082). In the azathioprine group there was a higher discontinuation rate due to adverse events compared to MMF (25.8% vs. 5.1%, resp., p = 0.018). There was no difference in the mean cumulative prednis (ol)one dose between the azathioprine group and MMF group (1834 mg (SD 544) vs.1944 mg (SD 475), resp., p = 0.369). Conclusion: In this prospective, randomised trial, MMF was superior to azathioprine for induction of remission in treatment‐naive patients with AIH. Adverse events led to cessation of the immuno‐modulator more often with azathioprine than with MMF. [Figure presented]