An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Background &amp; Aims: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. Methods: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Results: Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018). Conclusions: In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. Impact and implications: This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. Trial registration number: #NCT02900443.</p

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Background &amp; Aims: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. Methods: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Results: Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018). Conclusions: In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. Impact and implications: This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. Trial registration number: #NCT02900443.</p

MD 2408: Study of Schottky Monitors for Q' Measurement at Injection

The Schottky monitors installed at the LHC enable the detection of Schottky noise of the two circulating proton / ion beams. From Schottky noise, beam parameters like tune, chromaticity, and relative emittance, can be extracted in a non-destructive and purely parasitic method of measurement. The primary goal of this MD was to study the Schottky monitors capability to reliably and accurately determine the beam chromaticities at injection energy. Furthermore, the possibility to track the beam emittance has been investigated

MD 3290: Instability threshold measurements in the presence of a controlled external excitation

During the MD 2722 an unexpected instability was observed at flat top energy during BTF measurements. Simulation studies have shown an decrease of the instability thresholds according to the impedance level when in the presence of a small external excitation amplitude. In this note we summarise the results of the MD 3290 devoted to measure the instability thresholds in the presence of a controlled external excitation introduced by the use of the BTF system. The MD procedure is described and the presented results will be used as a reference in order to avoid instabilities during future BTF measurements at flat top energy

MD 751: Train Instability Threshold

The purpose of this MD is to measure the octupole current thresholds for stability for a single bunch, and then make an immediate comparison (with the same operational settings) for a train of 72 bunches separated by 25ns. From theory, the expected thresholds should be similar. Any discrepancy between the two cases will be of great interest as it could indicate the presence of additional mechanisms that contribute to the instability threshold, for example electron cloud

MD2065: Emittance exchange with linear coupling

In order to better understand the luminosity imbalance between ATLAS and CMS that was observed in 2016, it was proposed to perform a test whereby the horizontal and vertical emittances are exchanged by crossing the tunes in the presence of linear coupling. The luminosity before and after the exchange could be compared to see if the imbalance stems purely from the uneven emittances or if there is an additional mechanism in play. However, due to limited machine availability only tests at injection were able to performed

MD 754: Instability Threshold for Train with 25ns Spacing

Measurements made since the beginning of run II at 6.5 TeV have shown that there is a large discrepancy in the instability thresholds between single bunches and trains of 72 bunches with 25ns spacing, whereas the same result is expect for pure impedance-induced instabilities. One possible explanation is that the presence of electron cloud is affecting the beam stability. This MD will attempt to determine if electron cloud is the dominant mechanism affecting beam stability

MD 346: Summary of single bunch instability threshold measurements

The purpose of this MD is to measure the octupole current threshold to reach single-bunch stability in the LHC at flat top. Two bunches with dierent emittances are injected in the LHC in both B1 and B2 and the current in the Landau octupoles was progressively decreased until an instability developed. The measurements provide insight into the LHC impedance model by comparing them with the stabilizing octupole current predicted from DELPHI

First Beam Transfer Function measurements at LHC

For the first time in the LHC, Beam Transfer Function (BTF) measurements have been performed. Different machine configurations have been tested to determine the safety of the BTF measurement system that results to be completely transparent on single beam. To evaluate the spread given by different Landau octupole currents, an octupole current scan was performed. The data analysis is still ongoing. The BTF measurements have been tested also for beams in collision, the first attempt at 450 GeV resulted in the excitation of the beam-beam coherent -mode, while a second attempt at 6.5 GeV did not show any signs of instability. This is still under investigation and further tests are needed also with trains of bunches

MD 3292: Measurements of Landau Damping by Means of BTF Measurements

The methodology applied in previous MDs has shown the possibility of using BTFs measurements to estimate the transverse Landau Damping of the beams for different machine configurations. However, measurements with beam-beam interactions could not be performed during the past MDs. This note summarises the procedure and preliminary results of the MD 3292, carried out in two different MD Blocks (Block 3 and 4), during which BTF measurements in the presence of white noise and beam-beam interactions were acquired