Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score

Abstract

Background Drug-induced liver injury (DILI) represents an increasing morbidity in the general population, but more so in the elderly cohort of patients. Despite this, the concept of its prevention through prospective analysis has largely remained unexamined. We evaluated the utility of recently validated adverse drug reactions (ADR) avoidability tool in a cohort of elderly patients with DILI. Methods We examined 38 DILI-drug pairs from n=38 patients in a prospective cohort of patients presenting with adverse drug reactions to a Weill Cornell-affiliated tertiary hospital between February 2019 and January 2020. DILI outcomes were adjudicated by the updated Roussel Uclaf Causality Assessment Method (RUCAM). Two clinical pharmacologists and two general physicians utilized the Liverpool adverse drug reactions avoidability tool (LAAT) and the modified Hallas tools to rate the preventability of DILI-drug pairs. Inter-rater, exact agreement proportions, as well as intraclass correlation coefficients were generated and expressed as ordinal outcomes. Results The cases examined for the determination of DILI avoidability had probability likelihood of “probable” or “highly probable” by the updated RUCAM scale. Examination of the 38 DILI-drug pairs (n= 38 patients) resulted in a total of 152 ordinal outcome decisions. We found about 32.3% (50/152) and 34.2% (52/152) of DILI-drug pairs were rated as “avoidable” (“probable” or “definite”) by the LAAT and the modified Hallas tools respectively. The overall median Krippendorf’s kappa with the LAAT was 0.61 (SE 0.12, CI 0.36, 0.85) and for modified Hallas tool was 0.53 (SE 0.18; CI 0.16, 0.89). The inter-rater correlation coefficient (ICC) for the LAAT and modified Hallas were 0.50 [0.32, 0.65] and 0.63 [0.48, 0.76] respectively. Exact pairwise agreement was present in 30/38 (IQR 29.5, 34.5), and 28/38 (IQR 27.5-35.5) of DILI-ADR pairs using the LAAT and modified Hallas tools respectively. Conclusion We found a significant proportion of drug-induced liver injury adjudicated by the updated RUCAM scale in elderly hospitalized cohort of patients were avoidable with significant implication for therapeutic commissioning as well as cost effectiveness interventions in this cohort of patients.

An investigation into the avoidability of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome

“…The exact agreement proportions between the raters in terms of avoidability was about 80%; which will indicate excellent agreement. Our report is consistent with the agreement proportions reported by the original developers of the tool (9), as well subsequent validation studies (10,14,15). The proportionately higher interrater agreement and avoidability proportions (0.80) reported from our study compared to that by both Louise et al ( 9) and Danjuma et al (10) may be due to the phenotype of the clinical risks the tool (LAAT) was attempting to adjudicate.…”

“…The proportionately higher interrater agreement and avoidability proportions (0.80) reported from our study compared to that by both Louise et al ( 9) and Danjuma et al (10) may be due to the phenotype of the clinical risks the tool (LAAT) was attempting to adjudicate. The fact that DRESS syndrome has a distinct cutaneous clinical phenotype may have improved the degree of certainty in both the interrater agreement as well as avoidability determination outcomes compared to that seen with other ADR's (such as drug induced liver injury (15). We do concede that some forms of DRESS syndrome are idiosyncratic in manifestation and may not be amenable to adjuication of potenail avoidability.…”

“…The most recent Spanish Guidelines for diagnosis, management, treatment, and prevention of DRESS Syndrome made recommendations centered around added predictive values of speci c pharmacogenetic makers (such as single nucleotide polymorphisms) encoding implicated drugs (8). Recently, there has been a rising interest in the determination of the avoidability of adverse drug reactions (ADR) in the general population using novel "avoidability" determination algorithms/tools (9)(10)(11)(12). One of such tools is the Liverpool adverse drug reaction avoidability tool (LAAT) (9).…”

An investigation into the avoidability of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome

“…The most recent Spanish Guidelines for diagnosis, management, treatment, and prevention of DRESS Syndrome made recommendations centered around added predictive values of specific pharmacogenetic makers (such as single nucleotide polymorphisms) encoding implicated drugs 8 . Recently, there has been a rising interest in the determination of the avoidability of adverse drug reactions (ADR) in the general population using novel "avoidability" determination algorithms/tools [9][10][11][12] . One of such tools is the Liverpool adverse drug reaction avoidability tool (LAAT) 9 .…”

Comment: Drug-Induced Liver Injury (DILI) With Micafungin: The Importance of Causality Assessment

“…In an examination of 38 DILI-drug pairs (using the LAAT) from an elderly cohort of patients, we found that about 32.3% (50/152) of them were rated as “avoidable” (“probably” or “definitely”). 4 We found that the overall median Krippendorf’s κ with the tool was 0.61 (SE = 0.12; CI = 0.36, 0.85), with an interrater correlation coefficient of 0.50 [0.32, 0.65]. The demonstration of >32% of DILI cases as “avoidable” raises the prospect for further examination of these cases (including potentially micafungin cases) with the view to identifying areas for target therapeutic intervention.…”