Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis:Is the evidence of sufficient quality to develop recommendations?

BACKGROUND The standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce. AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). METHODS A systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI). RESULTS The pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups. CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement

Assessment of sex-related differences and outcome in patients who underwent cryoballoon pulmonary vein isolation for atrial fibrillation:an observational cohort study

OBJECTIVES: Pulmonary vein isolation (PVI) is widely accepted as an effective and safe treatment for symptomatic atrial fibrillation (AF). However, data on sex-related differences and associations with clinical outcome and safety of PVI with cryoballoon ablation are limited. We sought to compare sexrelated efficacy and safety of cryoballoon ablation and identify sex-related associations with clinical outcomes. METHODS AND RESULTS: We included 650 consecutive patients with AF undergoing PVI with cryoballoon ablation at our institution between 2013 and 2017. The efficacy outcome was the first documented recurrence (>30 s) of AF, atrial flutter or atrial tachycardia (AF/AT) or repeat ablation during follow-up, after a 90-day blanking period. The safety outcome was the incidence of periprocedural complications. Mean age of the population was 58±10, and 210 (32.3%) patients were women. Women were older, had a higher body mass index, had more renal dysfunction and less coronary artery disease as compared with men. The rate of AF/AT recurrence was similar between women and men at 12-month follow-up (27.6% vs 24.8%, p=0.445). The incidence of periprocedural complications was higher in women (12.9% vs 4.6%; p<0.001), specifically groin haematomas and phrenic nerve palsy. On multivariate analysis, left atrial volume index (adjusted OR 1.05, 95% CI 1.00 to 1.10; p=0.032) was associated with the incidence of procedural complications in women. For men, no relation with complications could be found. CONCLUSION: The efficacy of cryoballoon ablation was similar between women and men; however, women had a higher risk of procedural complications

Women have less progression of paroxysmal atrial fibrillation:data from the RACE V study

BACKGROUND: Sex differences in atrial fibrillation (AF) are observed in terms of comorbidities, symptoms, therapies received, AF progression and cardiovascular complications.METHODS: We assessed the differences in prevalence and the determinants of AF progression, as well as the clinical characteristics and quality of life (QoL), between women and men with paroxysmal AF included in the RACE V (Reappraisal of Atrial Fibrillation: Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilisation in the Progression of AF) study. At baseline, extensive phenotyping was done. To assess AF progression, implantable loop recorder (ILR) monitoring was used throughout follow-up. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of paroxysmal AF (&gt;3% burden increase).RESULTS: 417 patients were included, 179 (43%) of whom were women. Women were older (median 67 years vs 63 years, p&lt;0.001), less often had coronary artery disease (n=11 (6%) vs n=36 (16%), p=0.003), had more obesity (n=57 (32%) vs n=50 (21%), p=0.013), had less epicardial and pericardial fat (median 144 (interquartile range [IQR] 94-191) mL vs 199 (IQR 146-248) mL, p&lt;0.001; and median 89 (ICQ 61-121) mL vs 105 (IQR 83-133) mL, p&lt;0.001, respectively) and had more impaired left atrial function. The median follow-up was 2.2 (1.6-2.8) years. 51 of 417 patients (5.5% per year) showed AF progression (15/179 (8.4%) women and 36/238 (15.1%) men, p=0.032). Multivariable analysis showed tissue factor pathway inhibitor, N-terminal prohormone brain natriuretic peptide (NT-proBNP) and PR interval being associated with AF progression in women and factor XIIa:C1 esterase, NT-proBNP and proprotein convertase subtilisin/kexin type 9 in men. QoL was not different between sexes.CONCLUSION: Despite older age, the incidence of AF progression was lower in women. Parameters associated with AF progression varied in part between sexes, suggesting different underlying pathophysiological mechanisms.</p

Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis: Is the evidence of sufficient quality to develop recommendations?

BACKGROUND The standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce. AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). METHODS A systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI). RESULTS The pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups. CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement