Sepsis as a Possible Adverse Drug Reaction in Patients With Rheumatoid Arthritis Treated With TNFα Antagonists

Kling, Anders; Mjörndal, Tom; Rantapää‐Dahlqvist, Solbritt

doi:10.1097/01.rhu.0000128734.07926.8e

Cited by 15 publications

(6 citation statements)

References 16 publications

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“…At an individual level, health care providers assess causality informally when dealing with ADRs in patients to make decisions regarding therapy. Regulatory authorities assess spontaneous ADR reports [4], [5] where causality assessment can help in signal detection and aid in risk-benefit decisions regarding medicines [7], [8].…”

Section: Introductionmentioning

confidence: 99%

Development and Inter-Rater Reliability of the Liverpool Adverse Drug Reaction Causality Assessment Tool

et al. 2011

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AimTo develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT).MethodsA comparison between seven assessors of a new CAT, formulated by an expert focus group, compared with the Naranjo CAT in 80 cases from a prospective observational study and 37 published ADR case reports (819 causality assessments in total).Main Outcome Measures Utilisation of causality categories, measure of disagreements, inter-rater reliability (IRR).ResultsThe Liverpool ADR CAT, using 40 cases from an observational study, showed causality categories of 1 unlikely, 62 possible, 92 probable and 125 definite (1, 62, 92, 125) and ‘moderate’ IRR (kappa 0.48), compared to Naranjo (0, 100, 172, 8) with ‘moderate’ IRR (kappa 0.45). In a further 40 cases, the Liverpool tool (0, 66, 81, 133) showed ‘good’ IRR (kappa 0.6) while Naranjo (1, 90, 185, 4) remained ‘moderate’.ConclusionThe Liverpool tool assigns the full range of causality categories and shows good IRR. Further assessment by different investigators in different settings is needed to fully assess the utility of this tool.

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Section: Introductionmentioning

confidence: 99%

Development and Inter-Rater Reliability of the Liverpool Adverse Drug Reaction Causality Assessment Tool

et al. 2011

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“…Also, IL-6 deficiency leads to impaired immune responses against both viral and bacterial infection (42). Indeed, patients treated with TNF inhibitors or anti-IL-6 therapy are at an increased risk of developing certain infections (43)(44)(45)(46)(47). In the present study, sulfatide treatment efficiently downregulated expression of key cytokines, i.e., TNF-␣ and IL-6 in the cytokine storm during sepsis, but it did not prevent the immune response from clearing the microbes from different organs; there was even a tendency that sulfatide treatment decreased the bacterial load in kidneys on day 3 after bacterial inoculation.…”

Section: Figmentioning

confidence: 99%

Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

et al. 2013

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Natural killer T (NKT) lymphocytes are implicated in the early response to microbial infection. Further, sulfatide, a myelin selfglycosphingolipid, activates a type II NKT cell subset and can modulate disease in murine models. We examined the role of NKT cells and the effect of sulfatide treatment in a murine model of Staphylococcus aureus sepsis. The lack of CD1d-restricted NKT cells did not alter survival after a lethal inoculum of S. aureus. In contrast, sulfatide treatment significantly improved the survival rate of mice with S. aureus sepsis, accompanied by decreased levels of tumor necrosis factor alpha and interleukin-6 in the blood. The protective effect of sulfatide treatment depended on CD1d but not on type I NKT cells, suggesting that activation of type II NKT cells by sulfatide has beneficial effects on the outcome of S. aureus sepsis in this model.

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“…[188][189][190][191] At an individual level, health-care providers assess causality informally when dealing with ADRs in patients to make decisions regarding future therapy. Many regulatory authorities assess spontaneous ADR reports, 189,191 where causality assessment can help in signal detection and risk-benefit decisions regarding medicines, 192,193 using formal CATs to aid in this process.…”

Section: Introductionmentioning

confidence: 99%

ADRIC: Adverse Drug Reactions In Children – a programme of research using mixed methods

Smyth

Peak

Turner

et al. 2014

Programme Grants for Applied Research

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AimsTo comprehensively investigate the incidence, nature and risk factors of adverse drug reactions (ADRs) in a hospital-based population of children, with rigorous assessment of causality, severity and avoidability, and to assess the consequent impact on children and families. We aimed to improve the assessment of ADRs by development of new tools to assess causality and avoidability, and to minimise the impact on families by developing better strategies for communication.Review methodsTwo prospective observational studies, each over 1 year, were conducted to assess ADRs in children associated with admission to hospital, and those occurring in children who were in hospital for longer than 48 hours. We conducted a comprehensive systematic review of ADRs in children. We used the findings from these studies to develop and validate tools to assess causality and avoidability of ADRs, and conducted interviews with parents and children who had experienced ADRs, using these findings to develop a leaflet for parents to inform a communication strategy about ADRs.ResultsThe estimated incidence of ADRs detected in children on admission to hospital was 2.9% [95% confidence interval (CI) 2.5% to 3.3%]. Of the reactions, 22.1% (95% CI 17% to 28%) were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44 out of 249 (17.7%) of ADRs, the remainder originating from hospital. A total of 120 out of 249 (48.2%) reactions resulted from treatment for malignancies. Off-label and/or unlicensed (OLUL) medicines were more likely to be implicated in an ADR than authorised medicines [relative risk (RR) 1.67, 95% CI 1.38 to 2.02;p < 0.001]. When medicines used for the treatment of oncology patients were excluded, OLUL medicines were not more likely to be implicated in an ADR than authorised medicines (RR 1.03, 95% CI 0.72 to 1.48;p = 0.830). For children who had been in hospital for > 48 hours, the overall incidence of definite and probable ADRs based on all admissions was 15.9% (95% CI 15.0 to 16.8). Opiate analgesic drugs and drugs used in general anaesthesia (GA) accounted for > 50% of all drugs implicated in ADRs. The odds ratio of an OLUL drug being implicated in an ADR compared with an authorised drug was 2.25 (95% CI 1.95 to 2.59;p < 0.001). Risk factors identified were exposure to a GA, age, oncology treatment and number of medicines. The systematic review estimated that the incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children [pooled estimate of 2.9% (95% CI 2.6% to 3.1%)] and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. New tools to assess causality and avoidability of ADRs have been developed and validated. Many parents described being dissatisfied with clinician communication about ADRs, whereas parents of children with cancer emphasised confidence in clinician management of ADRs and the way clinicians communicated about medicines. The accounts of children and young people largely reflected parents’ accounts. Clinicians described using all of the features of communication that parents wanted to see, but made active decisions about when and what to communicate to families about suspected ADRs, which meant that communication may not always match families’ needs and expectations. We developed a leaflet to assist clinicians in communicating ADRs to parents.ConclusionThe Adverse Drug Reactions In Children (ADRIC) programme has provided the most comprehensive assessment, to date, of the size and nature of ADRs in children presenting to, and cared for in, hospital, and the outputs that have resulted will improve the management and understanding of ADRs in children and adults within the NHS. Recommendations for future research: assess the values that parents and children place on the use of different medicines and the risks that they will find acceptable within these contexts; focusing on high-risk drugs identified in ADRIC, determine the optimum drug dose for children through the development of a gold standard practice for the extrapolation of adult drug doses, alongside targeted pharmacokinetic/pharmacodynamic studies; assess the research and clinical applications of the Liverpool Causality Assessment Tool and the Liverpool Avoidability Assessment Tool; evaluate, in more detail, morbidities associated with anaesthesia and surgery in children, including follow-up in the community and in the home setting and an assessment of the most appropriate treatment regimens to prevent pain, vomiting and other postoperative complications; further evaluate strategies for communication with families, children and young people about ADRs; and quantify ADRs in other settings, for example critical care and neonatology.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

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Sepsis as a Possible Adverse Drug Reaction in Patients With Rheumatoid Arthritis Treated With TNFα Antagonists

Abstract: There is a need for more information to physicians to be aware of sepsis as a possible and serious ADR during treatment with TNF antagonists, and that patients with predisposing diseases or those who do not regularly visit their rheumatologist could be at higher risk.

Cited by 15 publications

References 16 publications

Development and Inter-Rater Reliability of the Liverpool Adverse Drug Reaction Causality Assessment Tool

Development and Inter-Rater Reliability of the Liverpool Adverse Drug Reaction Causality Assessment Tool

Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

ADRIC: Adverse Drug Reactions In Children – a programme of research using mixed methods

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