ALDRESS: A Retrospective Pilot Study to Develop a Pharmacological Causality Algorithm for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe form of drug hypersensitivity reaction characterized by significant morbidity, mortality, and long-term sequelae, coupled with limited therapeutic avenues. Accurate identification of the causative drug(s) is paramount for acute management, exploration of safe therapeutic alternatives, and prevention of future occurrences. However, the absence of a standardized diagnostic test and a specific causality algorithm tailored to DRESS poses a significant challenge in its clinical management. Methods: We conducted a retrospective case-control study involving 37 DRESS patients to validate a novel causality algorithm, the ALDRESS, designed explicitly for this syndrome, comparing it against the current standard algorithm, SEFV. Results: The ALDRESS algorithm showcased superior performance, exhibiting an 85.7% sensitivity and 93% specificity with comparable negative predictive values (80.6% vs. 97%). Notably, the ALDRESS algorithm yielded a substantially higher positive predictive value (75%) compared to SEFV (51.40%), achieving an overall accuracy rate of 92%. Conclusions: Our findings underscore the efficacy of the ALDRESS algorithm in accurately attributing causality to drugs implicated in DRESS syndrome. However, further validation studies involving larger, diverse cohorts are warranted to consolidate its clinical utility and broaden its applicability. This study lays the groundwork for a refined causality assessment tool, promising advancements in the diagnosis and management of DRESS syndrome.

Advancing pharmacogenetic testing in a tertiary hospital: a retrospective analysis after 10 years of activity.

The field of pharmacogenetics (PGx) holds great promise in advancing personalized medicine by adapting treatments based on individual genetic profiles. Despite its benefits, there are still economic, ethical and institutional barriers that hinder its implementation in our healthcare environment. A retrospective analysis approach of anonymized data sourced from electronic health records was performed, encompassing a diverse patient population and evaluating key parameters such as prescribing patterns and test results, to assess the impact of pharmacogenetic testing. A head-to-head comparison with previously published activity results within the same pharmacogenetic laboratory was also conducted to contrast the progress made after 10 years. The analysis revealed significant utilization of pharmacogenetic testing in daily clinical practice, with 1,145 pharmacogenetic tests performed over a 1-year period and showing a 35% growth rate increase over time. Of the 17 different medical departments that sought PGx tests, the Oncology department accounted for the highest number, representing 58.47% of all genotyped patients. A total of 1,000 PGx tests were requested for individuals susceptible to receive a dose modification based on genotype, and 76 individuals received a genotype-guided dose adjustment. This study presents a comprehensive descriptive analysis of real-world data obtained from a public tertiary hospital laboratory specialized in pharmacogenetic testing, and presents data that strongly endorse the integration of pharmacogenetic testing into everyday clinical practice.

Prognostic Impact of Dihydropyrimidine Dehydrogenase Germline Variants in Unresectable Non-Small Cell Lung Cancer Patients Treated with Platin-Based Chemotherapy.

Platin-based chemotherapy is the standard treatment for patients with non-small cell lung cancer (NSCLC). However, resistance to this therapy is a major obstacle in successful treatment. In this study, we aimed to investigate the impact of several pharmacogenetic variants in patients with unresectable NSCLC treated with platin-based chemotherapy. Our results showed that DPYD variant carriers had significantly shorter progression-free survival and overall survival compared to DPYD wild-type patients, whereas DPD deficiency was not associated with a higher incidence of high-grade toxicity. For the first time, our study provides evidence that DPYD gene variants are associated with resistance to platin-based chemotherapy in NSCLC patients. Although further studies are needed to confirm these findings and explore the underlying mechanisms of this association, our results suggest that genetic testing of DPYD variants may be useful for identifying patients at a higher risk of platin-based chemotherapy resistance and might be helpful in guiding future personalized treatment strategies in NSCLC patients.

Characterisation of Drug-Induced Liver Injury in Patients with COVID-19 Detected by a Proactive Pharmacovigilance Program from Laboratory Signals.

Coronavirus disease 2019 (COVID-19) has a wide spectrum of clinical manifestations. An elevation of liver damage markers has been observed in numerous cases, which could be related to the empirical use of potentially hepatotoxic drugs. The aim of this study was to describe the clinical and analytical characteristics and perform a causality analysis from laboratory signals available of drug-induced liver injury (DILI) detected by a proactive pharmacovigilance program in patients hospitalised for COVID-19 at La Paz University Hospital in Madrid (Spain) from 1 March 2020 to 31 December 2020. The updated Roussel Uclaf Causality Assessment Method (RUCAM) was employed to assess DILI causality. A lymphocyte transformation test (LTT) was performed on 10 patients. Ultimately, 160 patients were included. The incidence of DILI (alanine aminotransferase >5, upper limit of normal) was 4.9%; of these, 60% had previous COVID-19 hepatitis, the stay was 8.1 days longer and 98.1% were being treated with more than 5 drugs. The most frequent mechanism was hepatocellular (57.5%), with mild severity (87.5%) and subsequent recovery (88.1%). The most commonly associated drugs were hydroxychloroquine, azithromycin, tocilizumab and ceftriaxone. The highest incidence rate of DILI per 10,000 defined daily doses (DDD) was with remdesivir (992.7/10,000 DDD). Some 80% of the LTTs performed were positive, with a RUCAM score of ≥4. The presence of DILI after COVID-19 was associated with longer hospital stays. An immune mechanism has been demonstrated in a small subset of DILI cases.

A case report of a drug-induced liver injury (DILI) caused by multiple antidepressants with causality established by the updated Roussel Uclaf causality assessment method (RUCAM) and in vitro testing.

A 56-year-old female patient was hospitalized because of a lack of response and poor tolerance to multiple antidepressants, which included an episode of DILI. During hospitalization, the patient suffered another episode of DILI. Causality was assessed both by RUCAM and Lymphocyte Transformation Test, allowing to identify a safer medication.