Etanercept Therapy of Psoriatic Arthritis in a Patient with Liver Cirrhosis (original) (raw)
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Safety of Anti-Tumor Necrosis Factor Therapies in Arthritis Patients
Journal of Pharmacy and Pharmaceutical Sciences, 2014
Inflammatory and rheumatic arthritis remain leading causes of disability worldwide. The arthritis therapeutic area commands the largest market for the prescription of biological and non-steroidal anti-inflammatory drugs (NSAID). Yet biotechnology and pharmaceutical companies conducting research and providing therapeutics in this area frequently face challenges in patient safety. The purpose of our study was to assess safety of anti-tumor necrosis factor therapies in arthritis patients. Methods: The present study systematically reviews adverse events of biologicals alone or in the presence of NSAIDs and other immunosuppressant therapeutics such as disease-modifying antirheumatic drugs (DMARD). We assessed the rheumatology literature that included clinical trials with anti-tumor necrosis factor (TNF) biologicals and case reports published between 2010 and 2014. Results: Currently approved anti-TNF biologicals in arthritis include the monoclonal antibodies infliximab, adalimumab, certolizumab pegol and golimumab, and the fusion protein etanercept. The most frequently-reported adverse event was infection. We grouped the adverse reactions as immune-mediated, hypersensitivity syndrome reactions including cutaneous and hepatic manifestation, neurological, hematological, and malignancy. Discussion: Most adverse events are due to the failure of host immunological control, which involves susceptibility to the drug itself, or de novo infection or reactivation of a latent bacterial or viral infection, often with a different expression of disease. Drug-induced liver injury associated with anti-TNF biologicals must be kept in mind when evaluating patients with increased liver enzymes. Conclusion: Risk assessment in individuals undergoing treatment with biologicals represents a step towards achieving a personalized medicine approach to identify those patients that will safely benefit from this therapeutic approach. Patients and physicians must be alert of anti-TNF agents as potential causes of druginduced liver injury and monitor the therapies. Personalizing therapeutic pharmacovigilance promises to optimize benefits while minimizing side effects. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. ABBREVIATIONS ADA-anti-drug antibody AE-adverse event ADM-adalimumab ALP-alkaline phosphatase ALT-alanine aminotransferase ANA-antinuclear antibody anti-dsDNA-anti-double-stranded DNA antibody AST-aspartate aminotransferase AS-ankylosing spondylitis CNS-central nervous system CSF-cerebrospinal fluid CZP-certolizumab pegol DILI-drug-induced liver injury DMARD-disease-modifying anti-rheumatic drug ETN-etanercept γ-GTP-γ-glutamyl transpeptidase GLM-golimumab HBV-hepatitis B virus IFX-infliximab ILD-interstitial lung disease JIA-juvenile idiopathic arthritis LFT-liver function test MTX-methotrexate NSAID-non-steroidal anti-inflammatory drug PML-progressive multifocal leukoencephalopathy RA-rheumatoid arthritis RF-rheumatoid factor TB-tuberculosis Th-T helper TNF-tumor necrosis factor
The reverse of the coin: Methotrexate and liver fibrosis in a group of psoriatic arthritis patients
Romanian Journal of Rheumatology, 2020
Objectives. We aimed to assess the presence of liver fibrosis using transient elastography in a group of PsA patients, compared to controls, and its possible relationship with MTX treatment. Methods. We performed a prospective study on 41 patients diagnosed with PsA admitted to the Rheumatology Department of the Emergency County Hospital Craiova and a control group, of 20 sex and age-matched subjects. Patients data included demographic, clinical and laboratory parameters and were collected from every patient in accordance to the study protocol. Liver stiffness was evaluated using transient elastograhy, by an experienced investigator, using Fibroscan system (Echosens, Paris, France). Results. After assessing liver fibrosis (LF) by transient elastography, we obtained statistically significant values compared to controls (6.04+1.65 kPa vs 4.16 +0.93 kPa, p = 0.002); liver fibrosis was found in 11 patients (26.81%), 9 of them undergoing MTX treatment. Analyzing the impact of MTX treatment, we found statistically significant values between the two groups (6.04+1.65 kPa for MTX treated group vs 5.35+1.30kPa, p = 0.03 for non-MTX patients). Analyzing the differences between patients with/without liver fibrosis, we reckoned the following data: no differences for sex, age, alcohol consumption, hypertension, diabetes or hepatic function; significant differences were observed for BMI, dyslipidemia and fatty liver. Conclusions. Hepatic involvement, especially liver fibrosis might be underestimated in PsA patients, and it is necessary to be properly and periodically evaluated in order to prevent further complications and maintain the efficient and safe dose of MTX, the first line therapeutic agent chosen for these patients. Non invasive hepatic imaging methods, such as transient elastography should certainly be considered for screening, along with a proper monitoring of comorbidities.
International Journal of Clinical Rheumatology, 2019
psoriasis and has immunomodulatory activity against inflammatory arthritis [3]. MTX is now the most popular anchor cornerstone drug for the treatment of RA worldwide. Low-dose, weekly MTX (10 to 25 mg/week) used as either monotherapy or in combination with other drugs as other DMARDs, biologic therapy or targeted biological therapies. It has a superior efficacy profile comparable with other drugs [4]. MTX is well tolerated; gastrointestinal toxicity is the most common toxicity with rarely bone marrow, lung, or liver toxicity [5]. Long term therapy with MTX has been associated with development of fatty liver and hepatic fibrosis and in rare instances portal hypertension and symptomatic cirrhosis. Symptoms are usually absent until cirrhosis is present and liver tests are typically normal or minimally and transiently elevated. Routine monitoring of patients with regular liver biopsies
Rheumatology International, 2012
Tumour necrosis factor-alpha (TNF-a) inhibitors are widely used in the management of patients with rheumatoid arthritis (RA) and spondylarthritides. However, TNF-a inhibition may lead to adverse events, including liver injury. The RA patients are frequently treated with several potentially hepatotoxic drugs concomitantly; hence, a causative link between TNF-a inhibitors and liver injury is usually difficult to establish. We report two cases of RA patients who developed histologically manifest liver injury shortly after the introduction of treatment with two different TNF-a inhibitors. Furthermore, we present the analysis of the laboratory data from the BioRx.si registry (the Slovenian national registry of rheumatologic patients treated with biologicals) and provide evidence that elevated levels of serum aminotransferase can be observed in patients treated with TNF-a inhibitors. Additionally, our analysis suggests no significant differences between the impact of adalimumab and etanercept on aminotransferase levels. Although the use of TNF-alpha inhibitors is safe and efficient, we suggest that continuous careful monitoring of aminotransferase levels in patients treated with these agents is probably warranted.
Treatment of rheumatoid arthritis patients – a challenge
Romanian Journal of Rheumatology, 2020
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune disease with unclear etiology that involves the peripheral joints symmetrically, causing synovial hypertrophy, inflammation and, consequently, erosions of the bone and cartilage. We hereby present the case of a 51-year-old female patient diagnosed with RA in 2009 for which she received treatment with Methotrexate and TNF alpha treatment (Infliximab). Prior to the first dose of Infliximab Quantiferon-TB Gold was performed with a negative result. In 2016 the patient presented with ascites and pleural effusion with a positive repeated test for Quantiferon-TB Gold, the treatment with Infliximab and Methotrexate was stopped and she was started on anti TB standard treatment regimen for 9 months with the remission of the polyserositis. After the completion of the anti TB treatment we reinitiated Methotrexate therapy given a high disease activity (DAS28-CRP of 6.59) which improved the patients complaints; however, 3 months later, given an increase in the patients inflammatory markers we performed a computed tomography (CT) scan that revealed peritoneal thickening, and several omental nodules, the histological examination confirming the diagnosis of peritoneal TB. The patient was reinitiated on the anti-TB treatment.
Annals of the Rheumatic Diseases, 2010
Introduction-Potential hepatotoxicity associated with disease modifying anti-rheumatic drugs [DMARDs] requires laboratory monitoring. In rheumatoid and psoriatic arthritis [RA, PsA] patients, we examined the incidence of elevated alanine/aspartate aminotransferase (ALT/AST) enzymes associated with methotrexate (MTX), leflunomide (LEF), and MTX+LEF vs. other DMARDs. either was 1 or 2-fold time above the upper limits of normal (ULN). Odds ratios [OR] between MTX/ LEF dose and elevated ALT/AST enzymes were estimated using generalized estimating equations. Interaction terms for use of MTX+LEF quantified the incremental risk of the combination compared to each individually.