Dataset Information

Safety Profile of Biologics Used in Rheumatology: An Italian Prospective Pharmacovigilance Study.

ABSTRACT: Post-marketing surveillance activities are essential to detect the risk/benefit profile of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthritis. The aim of this study was to evaluate adverse events (AEs) in patients treated with bDMARDs in rheumatology during a prospective pharmacovigilance study from 2016 to 2018. Descriptive statistical analyses were performed to evaluate bDMARDs-related variables of patients without AEs/failures vs patients with AEs and failures. The risk profile among biologics was assessed by comparing patients treated with each bDMARD to patients treated with etanercept. A total of 1155 patients were enrolled, mostly affected by rheumatoid arthritis (46.0%). AEs and failures were experienced by 8.7% and 23.3%, respectively. The number of comorbidities significantly influenced the onset of AEs, while anxiety-depressive, gastrointestinal disease, and fibromyalgia influenced onset of failures. The probability of developing an AE was significantly lower in patients treated with secukinumab, while the probability of developing treatment failure was significantly lower in patients treated with golimumab, secukinumab and tocilizumab. A total of 216 AEs were reported (25.5% serious), mostly regarding infections (21.8%), musculoskeletal (17.6%) and skin (16.2%) disorders. Serious AEs included neutropenia (12.7%), lymphocytosis (9.1%) and uveitis (7.3%). The obtained results revealed known AEs but real-world data should be endorsed for undetected safety concerns.

SUBMITTER: Barbieri MA

PROVIDER: S-EPMC7230621 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Safety Profile of Biologics Used in Rheumatology: An Italian Prospective Pharmacovigilance Study.

Barbieri Maria Antonietta MA Cicala Giuseppe G Cutroneo Paola Maria PM Gerratana Elisabetta E Palleria Caterina C De Sarro Caterina C Vero Ada A Iannone Luigi L Manti Antonia A Russo Emilio E De Sarro Giovambattista G Atzeni Fabiola F Spina Edoardo E

Journal of clinical medicine 20200424 4

Post-marketing surveillance activities are essential to detect the risk/benefit profile of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthritis. The aim of this study was to evaluate adverse events (AEs) in patients treated with bDMARDs in rheumatology during a prospective pharmacovigilance study from 2016 to 2018. Descriptive statistical analyses were performed to evaluate bDMARDs-related variables of patients without AEs/failures vs patients with AEs and failures. ...[more]

PMID: 32344563

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Project description:Psoriasis is an inflammatory and chronic skin disorder associated with physical and psychological burden impairing patients' quality of life. In the last decade, biologic drugs have widely changed treatment of moderate-severe psoriasis and their number is increasing overtime. To early identify expected/unexpected adverse events (AEs) with biologic treatments, pharmacovigilance programs are needed. We designed a post-marketing active pharmacovigilance program to monitor and analyse AEs and/or serious adverse events (SAEs) reports. All consecutive patients treated with one biologic drug during a two-years period and satisfying inclusion criteria have been enrolled in five Dermatology tertiary units. Demographic and clinical features of patients, type of treatment used, therapy discontinuation, failures, switch/swap to another biologic, and possible onset of AEs were collected. Overall, 512 patients with a diagnosis of psoriasis (286; 55.9%) or arthropathic psoriasis (226; 44.1%) have been enrolled. Eighty-two (16%) patients with AEs and 5 (1%) with SAEs have been identified. Further, 59 (11.5%) had a primary/secondary failure (mainly on infliximab and etanercept). The adverse events and SAEs were reported with golimumab (4/12), adalimumab (32/167), infliximab (9/48), etanercept (31/175) and ustekinumab (11/73), no adverse events have occurred with secukinumab (0/37). Infliximab and etanercept were significantly associated with primary/secondary failures, whereas no differences have been highlighted for AEs insurgence. On the other hand, ustekinumab seems to be associated with a low rate of AEs (p = 0.01) and no adverse events or failures have been reported with secukinumab (p = 0.04 and 0.03, respectively). Our study, even though limited by a small sample size and a brief follow-up period, provide useful data on widely used biologic drugs and their tolerability, discontinuation rate and the incurrence of severe adverse events. Further studies are necessary to include the recently approved biologic drugs and to increase the sample size for more detailed analysis.

Project description:IntroductionNon-small cell lung cancer (NSCLC) is often caused by molecular alterations that can be detected by predictive biomarkers including mutations or amplifications of several genes. Several tyrosine kinase inhibitors (TKIs) have been approved in Europe by the European Medicines Agency (EMA) for NSCLC. The aim of this study was to analyze the onset of adverse drug reactions (ADRs) related to TKIs in NSCLC through a spontaneous reporting system (SRS) database.MethodsAll ADR reports having as suspected drug afatinib (AFT), alectinib (ALEC), brigatinib (BRG), ceritinib (CER), crizotinib (CRIZ), erlotinib (ERL), gefitinib (GEF), lorlatinib (LORL), nintedanib (NTB), and osimertinib (OSI) recorded into the Report Reazioni Avverse dei Medicinali (RAM) system database for national data and into the Italian SRS database for Sicilian data and collected from 2006 to 2021 have been evaluated. A descriptive analysis of basal demographic and drug-related characteristics was performed. A case-by-case methodology was conducted paying particular attention to all serious ADR reports collected in Sicily, focusing on type of seriousness, age, sex, concomitant drugs, and comorbidities.ResultsOf the 3,048 Italian reports, most of ADRs were related to ERL (n = 1,448), followed by AFT (n = 435) and GEF (n = 366). ADR reports were slightly more frequent in females (52.2%) and in the age group >65 years (53.0%). A higher number of cases were related to skin disorders (n = 1,766; 57.9%), followed by gastrointestinal disorders (n = 1,024; 33.6%), general disorders and administration site conditions (n = 536; 17.6%), and infections (n = 483; 15.8%). The case-by-case assessment of Sicilian ADRs showed that 33 cases were serious (12.5%) and mainly involved ERL (n = 17; 51.5%), occurring in males with a higher onset of respiratory diseases (30.3%) such as respiratory failure, interstitial lung disease and dyspnea.DiscussionThe analysis of spontaneous ADR reports of TKIs confirmed, in general, well-known risks, which often include skin, gastrointestinal, general, liver, and respiratory diseases as well as infections. However, more attention should be paid to the occurrence of serious life-threatening ADRs including respiratory failure, interstitial lung disease, and cardiogenic shock, especially in young patients.

Project description:In light of the favorable outcomes of few small, non-randomized clinical studies, the Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to Hydroxychloroquine (HCQ) for hospitalized coronavirus disease 2019 (COVID-19) patients. In fact, subsequent clinical studies with COVID-19 and HCQ have reported limited efficacy and poor clinical benefits. Unfortunately, a robust clinical trial for its effectiveness is not feasible at this emergency. Additionally, HCQ was suspected of causing cardiovascular adverse reactions (CV-AEs), but it has never been directly investigated. The objective of this pharmacovigilance analysis was to determine and characterize HCQ-associated cardiovascular adverse events (CV-AEs). We performed a disproportionality analysis of HCQ-associated CV-AEs using the FDA adverse event reporting system (FAERS) database. The FAERS database, comprising more than 11,901,836 datasets and 10,668,655 patient records with drug-adverse reactions, was analyzed. The disproportionality analysis was used to calculate the reporting odds ratios (ROR) with 95% confidence intervals (CI) to predict HCQ-associated CV-AEs. HCQ was associated with higher reporting of right ventricular hypertrophy (ROR: 6.68; 95% CI: 4.02 to 11.17), left ventricular hypertrophy (ROR: 3.81; 95% CI: 2.57 to 5.66), diastolic dysfunction (ROR: 3.54; 95% CI: 2.19 to 5.71), pericarditis (ROR: 3.09; 95% CI: 2.27 to 4.23), torsades de pointes (TdP) (ROR: 3.05; 95% CI: 2.30 to 4.10), congestive cardiomyopathy (ROR: 2.98; 95% CI: 2.01 to 4.42), ejection fraction decreased (ROR: 2.41; 95% CI: 1.80 to 3.22), right ventricular failure (ROR: 2.40; 95% CI: 1.64 to 3.50), atrioventricular block complete (ROR: 2.30; 95% CI: 1.55 to 3.41) and QT prolongation (ROR: 2.09; 95% CI: 1.74 to 2.52). QT prolongation and TdP are most relevant to the COVID-19 treatment regimen of high doses for a comparatively short period and represent the most common HCQ-associated AEs. The patients receiving HCQ are at higher risk of various cardiac AEs, including QT prolongation and TdP. These findings highlight the urgent need for prospective, randomized, controlled studies to assess the risk/benefit ratio of HCQ in the COVID-19 setting before its widespread adoption as therapy.

Project description:Given the importance of inflammation at the onset of multiple sclerosis (MS), therapy is mainly based on the use of anti-inflammatory drugs including disease modifying therapies (DMTs). Considering the recent approval of some DMTs, pharmacovigilance becomes a fundamental tool for the acquisition of new safety data. The aim of the study was to analyze adverse drug reactions (ADRs) related to the use of drugs approved for MS. All national publicly-available aggregated ADR reports recorded from 2002 to 2020 into the Reports of Adverse Reactions of Medicines (RAM) system and all complete Sicilian data reported into the Italian spontaneous reporting system (SRS) database having as suspected drugs interferon β-1a (IFN β-1a), interferon β-1b (IFN β-1b), peginterferon β-1a (PEG-IFN β-1a), glatiramer acetate (GA), natalizumab (NTZ), fingolimod (FNG), teriflunomide (TRF), dimethyl fumarate (DMF), alemtuzumab (Alem), ocrelizumab (OCZ), or cladribine (Cladr), were collected. Descriptive analyses of national, publicly-available aggregated data and full-access regional data were performed to assess demographic characteristics and drug-related variables followed by a more in-depth analysis of all Sicilian ADRs with a case-by-case assessment and a disproportionality analysis of unexpected ADRs. A total of 13,880 national reports have been collected from 2002 to 2020: they were mainly not serious ADRs (67.9% vs. 26.1%) and related to females (71.7% vs. 26.3%) in the age group 18-65 years (76.5%). The most reported ADRs were general and administration site conditions (n = 6,565; 47.3%), followed by nervous (n = 3,090; 22.3%), skin (n = 2,763; 19.9%) and blood disorders (n = 2,180; 15.7%). Some unexpected Sicilian ADRs were shown, including dyslipidemia for FNG (n = 10; ROR 28.5, CI 14.3-59.6), NTZ (n = 5; 10.3, 4.1-25.8), and IFN β-1a (n = 4; 8.7, 3.1-24.1), abortion and alopecia for NTZ (n = 9; 208.1, 73.4-590.1; n = 3; 4.9, 1.5-15.7), and vitamin D deficiency for GA (n = 3; 121.2, 30.9-475.3). Moreover, breast cancer with DMF (n = 4, 62.8, 20.5-191.9) and hypothyroidism with Cladr (n = 3; 89.2, 25.9-307.5) were also unexpected. The reporting of drugs-related ADRs in MS were mostly reported in the literature, but some unknown ADRs were also found. However, further studies are necessary to increase the awareness about the safety profiles of new drugs on the market.

Project description:BackgroundStatins play an important role in the care of patients with cardiovascular disease and have a good safety record in clinical practice. Hepatotoxicity is a barrier that limits the ability of primary care physicians to prescribe statins for patients with elevated liver transaminase values and/or underlying liver disease. However, limited population-based data are available on the use of statin therapy and on the hepatotoxicity of statins in very elderly patients. This prospective study evaluated the liver enzyme elevation during statin therapy in very elderly patients (≥80 years old).MethodsPatients with hypercholesterolemia (LDL-C levels ≥3.4 and < 5.7 mmol/L), atherosclerosis, coronary heart disease (CHD), or a CHD-risk equivalent were enrolled and received once-daily statin treatment. Multivariate logistic regression models were used to study the impact of age, gender, hepatitis B infection, fatty liver disease, biliary calculus, other chronic diseases, drug kinds, alcohol abuse, statin variety, and statin dose variables.ResultsA total of 515 consecutive patients ranging from 80 to 98 years old were included in the analysis. These patients were treated with simvastatin, fluvastatin, pravastatin, rosuvastatin, or atorvastatin. Twenty-four patients (4.7, 95% CI 2.7-6.6) showed an increase in their hepatic aminotransferase levels. No significant difference of hepatic aminotransferase elevation rates was observed in different statin treatment groups. The incidence of mild, moderate, and severe elevation of aminotransferase levels was 62.5% (15/24), 29.2% (7/24), and 8.3% (2/24), respectively. None of the patients developed hepatic failure. Nine patients with moderate or severe aminotransferase elevations discontinued therapy. The time of onset of hepatic aminotransferase elevation ranged from 2 weeks to 6 months after statin treatment. The onset of hepatic aminotransferase elevation was within 1 month for 70.8% of patients. The patients took 2 weeks to 3 months to recover their liver function after statin therapy cessation. Multivariate analysis identified chronic hepatitis B infection and alcohol consumption as independent factors associated with the hepatic response to statins: OR, 12.83; 95% CI (4.36-37.759) and OR, 2.736; 95% CI (1.373-5.454), respectively.ConclusionThe prevalence of elevated transaminases was higher than published data in very elderly patients. Overall, statin treatment is safe for patients ≥80 years old.

Dataset Information

Safety Profile of Biologics Used in Rheumatology: An Italian Prospective Pharmacovigilance Study.

Publications

Safety Profile of Biologics Used in Rheumatology: An Italian Prospective Pharmacovigilance Study.

Similar Datasets

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