"Hepatic toxicity by methotrexate with weekly single doses associated with folic acid in rheumatoid and psoriatic arthritis. What is its real frequency?"

INTRODUCTION AND OBJECTIVES: Liver injury caused by methotrexate (MTX) has mostly been investigated without applying criteria for the assessment of causality of drug induced liver injury (DILI). Hence, the existence of DILI by MTX in many cases is debatable. This study aimed to describe the frequency and characteristics of liver injury caused by MTX, applying DILI diagnostic criteria. MATERIAL AND METHODS: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients who were treated with MTX in association with folic acid were included. Serial determinations of alanine amino transferase (ALT) and aspartate amino transferase (AST) were performed. The Roussel Uclaf Causality Assessment Method (RUCAM) was applied in cases of increases of ALT/AST over 1.5 upper limit of normal. Liver biopsy was considered when the total cumulative dosage (TCD) of MTX was ≥3.5g. RESULTS: A total of 43 patients were analyzed (median follow up 32 (range: 1-48) months; 3.33 ALT/AST determinations per year). Five subjects presented an increase of ALT/AST. All presented a RUCAM score for MTX≤2 (improbable). Three had a RUCAM score for non-steroidal anti-inflammatory drugs ≥7 (probable) and two patients presented non-alcoholic fatty liver disease. Five patients with no other cause for liver disease consented to liver biopsy (TCD MTX: median 5.1; range: 3.5-7.4g). No significant fibrosis or steatosis was evident on histology. CONCLUSIONS: No biochemical or significant histological liver toxicity for MTX was demonstrated when applying causality criteria for DILI. More studies with this methodology are necessary in order to improve the assessment of its frequency.

Rheumatoid arthritis monotherapy in the Jak inhibitors Era. Current prevalence and associated factors in a multicenter study.

BACKGROUND: Combined therapy constitutes the standard of care in RA. Jak inhibitors (Jaki) have shown efficacy in monotherapy, a modality used in cases where it is not possible to use Disease-Modifying Anti Rheumatic Drugs (csDMARDs). OBJECTIVES: To estimate the prevalence (total and by drug), reason for using and the increase over the time of bDMARDs or tsDMARDs as monotherapy after the availability of the Jaki. To analyze the differential characteristics between patients with monotherapy vs combined therapy. METHODS: Cross-sectional multicenter study. Consecutive patients with a diagnosis of RA (ACR/EULAR 2010) under treatment with bDMARDs or tsDMARDs started from 2013 were included. Socio-demographic, clinic, and therapeutic data were collected. RESULTS: A total of 505 RA patients were included. Since 2013, the prevalence of monotherapy usage was (any) 49%. The drugs used as monotherapy were Jaki in 41% and TNF-blockers in 30%. The leading causes of monotherapy use were intolerance/adverse events (62%), medical decision or lack of adherence (37.7%). The highest socioeconomic level and a better functional status at diagnosis were predictors of monotherapy use. The use of the second line of treatments and less polypharmacy were independent factors associated with this therapeutic modality. CONCLUSIONS: The current prevalence of monotherapy in RA was 49%, the Jaki were the most used drug in this modality. Monotherapy increases from year to year. There are differential characteristics in patients using monotherapy.

[Liver diseases in rheumatoid and psoriatic arthritis]. / Enfermedades hepáticas en artritis reumatoidea y psoriásica.

OBJECTIVE: The aim of this study was to evaluate the prevalence, risk factors and features of liver diseases (LD) in rheumatoid and psoriatic arthritis. PATIENTS AND METHODS: From July 2007 to January 2010, 118 non-selected patients were consecutively examined. The assessment consisted of a medical record, biochemical studies and abdominal ultrasounds. The diagnosis of fatty liver disease was based on the ultrasound drug induced liver injury (DILI) was evaluated by the Maria-Victorino system criteria. Liver biopsy associated with chronic administration of methotrexate was performed using the histological classification of Kleiner et al. For the statistical analysis chi square test with Yates correction, Student's t test or Mann-Whitney test were applied when appropriate. In the multivariate analysis a binary logistic regression was used. The threshold of significance was P < 0.05. RESULTS: LD was diagnosed in 47 patients (39.8%). The most frequent LD was fatty liver disease in 35 patients (29.7%), followed by DILI in 15 (12.7%), associated with non-steroidal anti-inflammatory drugs (NSAID). In the multivariate analysis, obesity was the only independent risk factor associated with fatty liver disease [Odds ratio (OR) 6.4 (confidence interval (CI) 95%: 2.5-16.1; P = 0.000)] and fatty liver disease was the only risk factor associated with DILI [OR 7.7 (CI 95%: 2.0-30.0; P = 0.003)]. CONCLUSIONS: In our series, there was a high prevalence of LD, being fatty liver disease associated with obesity the most frequent finding. The second frequent disease was DILI, being fatty liver disease its main risk factor. The presence of obesity and the use of NSAIDs, especially in patients with steatosis, arise from our results as two conditions that require special care in handling this particular population.