Drugs - Real World Outcomes最新文献

Background: Although Janus kinase (JAK) inhibitors have expanding indications, deep vein thrombosis (DVT) and pulmonary embolism (PE) are serious adverse events associated with their use. Moreover, their analysis using the Japanese database of spontaneous adverse drug reaction reports has not yet been conducted.

Objective: The objective of this study was to analyze the Japanese Adverse Drug Event Report database (JADER) to evaluate the association between JAK inhibitors and DVT and PE.

Methods: JADER reports from April 2004 to October 2023 were analyzed. A classification of reports for the period covered was performed by drug, and an imbalance analysis was performed with oral JAK inhibitors as the target drug and DVT, PE, and "embolic and thrombotic events, venous" (Standardised MedDRA Query; SMQ) as the target adverse events. Reported odds ratios (ROR) and information components (IC) were calculated for signal detection.

Results: Overall, 6631 JAK inhibitor-related adverse events were reported, including 60 and 41 cases of DVT and PE, respectively. The ROR and IC of the JAK inhibitors for DVT were 2.52 (1.95-3.25) and 1.27 (0.41-2.13), while those of baricitinib for DVT were 4.37 (2.83-6.73) and 1.90 (0.47-3.33), respectively. ROR signals were detected for JAK inhibitors for PE and "embolic and thrombotic events, venous (SMQ)," overall and for several JAK inhibitors but none for IC.

Conclusions: Several JAK inhibitors are under postmarketing phase vigilance, and the number of reported adverse events is low. However, when administering these drugs, care should be taken to avoid the development of thromboembolism, considering the patient's background.

Background: The prognosis of patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer has improved significantly since the advent of EGFR tyrosine kinase inhibitors (EGFR-TKIs). We aimed to investigate the relationship between patient characteristics, EGFR genotype, therapeutic agents, and the prognosis of the patients with EGFR mutation-positive lung cancer.

Methods: This retrospective cohort study analyzed 198 Japanese patients with unresectable EGFR mutation-positive lung cancer who were treated with EGFR-TKIs at Toho University Sakura Medical Center from April 2006 to December 2021. Factors associated with overall survival (OS) were analyzed using Cox proportional hazards analysis.

Results: Patients who received osimertinib had a significantly longer OS than did those not receiving it (median OS, 36.2 versus 20.7 months; p < 0.001).There were significant differences in OS between patients with EGFR mutation who received osimertinib as first-line treatment, T790M-positive patients who received osimertinib as second- or later-line treatment, and those who did not receive it (median OS, 28.2 versus 40.2 versus 20.7 months; p = 0.003). However, in T790M-negative patients, no significant difference in OS was noted between those who did and did not receive osimertinib as post-treatment (median OS, 28.0 versus 40.0 months; p = 0.619). Multivariate Cox proportional hazards analysis showed that osimertinib treatment was associated with longer OS (hazard ratio, 0.480; 95% confidence interval, 0.326-0.707; p < 0.001).

Conclusion: The patients who were T790M-positive in the first-line treatment with first or second-generation EGFR-TKIs and were given osimertinib as the second or later line treatment had a better prognosis than the patients who were T790M-negative in the first-line treatment with first or second-generation EGFR-TKIs and could not receive osimertinib.

Introduction: The association between omeprazole and hypertension is poorly documented. The summary of product characteristics of omeprazole approved by major regulators did not mention hypertension as an adverse drug event. Triggered by a locally reported case, this study was conducted to assess the possible causal relationship between omeprazole and hypertension.

Methods: Globally reported cases of hypertension following use of omeprazole submitted to the World Health Organization global database, VigiBase, were retrieved on 5 March 2024 and analyzed descriptively. Besides this, a literature search was made to identify preclinical, clinical, and epidemiological information on the association between omeprazole and hypertension or increased blood pressure using different data sources. Relevant information, gathered from different data sources, was finally systematically organized into an Austin Bradford-Hill causality assessment framework to assess the causal relationship between omeprazole and hypertension.

Results: VigiBase indicated a total of 1043 cases of hypertension related to omeprazole from 36 different countries. In the global database, a statistical signal was triggered (IC₀₂₅: 0.12) on association of omeprazole and hypertension. From the 1043 cases, 65.0% and 10.6% were reported as 'serious' and 'fatal', respectively. Hypertension resolved following withdrawal of omeprazole in 85 cases and recurred after re-introduction of the suspect drug in 14 cases. In 225 cases, omeprazole was the only suspected drug, while in 122 cases, omeprazole was the sole drug administered. When only these 122 cases were considered, 29 cases had positive dechallenge, four cases were with positive rechallenge and the median time-to-onset was 2 days. Literature search identified a possible biological mechanism and some experimental evidence that indicates omeprazole could possibly cause hypertension.

Conclusion: Currently available totality of evidence suggests there is a possible causal relationship between omeprazole and hypertension. Hence, it is recommended to monitor and report any incidence of hypertension related to omeprazole, and further epidemiological studies are recommended to corroborate the suggested causal association.

Background: This study aimed to understand treatment patterns, acute healthcare use, and cost patterns among adults with treatment-resistant depression (TRD) who completed induction treatment with esketamine nasal spray in the United States (US). Per label, induction is defined as administration twice a week for 4 weeks, after which maintenance is started on a weekly basis for 4 weeks, and thereafter, patients are treated weekly or bimonthly.

Methods: Adults with one or more esketamine claim (index date) on or after March 5, 2019 were selected from Optum's de-identified Clinformatics^® Data Mart Database (January 2016-June 2022). Before the index date, patients had evidence of TRD and ≥ 12 months of continuous insurance eligibility (baseline period). Patients with eight or more esketamine treatment sessions were included in the main cohort. A subgroup included patients with one or more baseline mental health (MH)-related inpatient (IP) admission or emergency department (ED) visit (i.e., prior acute healthcare users). Treatment patterns were described during the follow-up period (index date until earliest of end of insurance eligibility or data); acute healthcare (i.e., IP and ED) resource use and costs (2021 US dollars) were reported during the baseline and follow-up periods.

Results: Of the 322 patients in the main cohort, 111 comprised the subgroup of prior acute healthcare users. During the follow-up period, mean time from index date to eighth esketamine session was 73.2 days in the main cohort and 78.8 days in the subgroup (per label, 28 days). Further, 75.2% of the main cohort and 73.9% of the subgroup completed four or more esketamine maintenance sessions following induction. In the main cohort, mean all-cause acute healthcare costs per patient per month (PPPM) decreased from baseline ($837) to follow-up ($770). Similar reductions were observed for mean MH-related acute healthcare costs PPPM (baseline $648, follow-up $577). In the subgroup, mean all-cause acute healthcare costs PPPM also decreased (baseline $2323, follow-up $1423), driven by mean MH-related acute healthcare costs PPPM (baseline $1880, follow-up $1139). Mean all-cause acute healthcare use per ten patients per month remained largely stable from baseline to follow-up in the main cohort (IP days: baseline 2.24, follow-up 2.13; ED visits: baseline 1.33, follow-up 1.45) and decreased in the subgroup (IP days: baseline 6.38, follow-up 4.56; ED visits: baseline 2.58, follow-up 2.41). Trends in mean MH-related acute healthcare use were similar.

Conclusion: Patients generally required more time than label recommendation to complete esketamine induction treatment, and most went on to have 12 or more esketamine sessions. Completion of induction treatment correlated with reductions in mean all-cause and MH-related acute healthcare costs. Larger reductions were seen in the subgroup of prior

Background: Levetiracetam is an anti-seizure medication (ASM) with an established safety profile. However, a potential safety signal of hypokalemia following levetiracetam use was published in the World Health Organization newsletter.

Objective: To investigate the possible causal association between the use of levetiracetam and the development of hypokalemia.

Method: This was a new-user, active-comparator retrospective cohort study using Real-world Evidence Research Network data at the Saudi Food and Drug Authority from 2016 to 2022. Adults (≥ 18 years old) with an incident prescription for either levetiracetam or carbamazepine were followed for up to 6 months from the prescription date. Hypokalemia was ascertained by using diagnostic code (i.e., E87.6) or by serum potassium level below 3.5 mmol/L. A Cox proportional hazards model, adjusted with stabilized inverse probability of treatment weight, was fitted to compare the hazard of hypokalemia between levetiracetam and carbamazepine exposed patients.

Results: A total of 8,982 patients entered the study cohort. The incidence rate of hypokalemia was 303 cases per 10,000 patient-years in the levetiracetam-exposed cohort compared to 57 cases per 10,000 patient-years among carbamazepine users. Compared to carbamazepine users, patients exposed to levetiracetam had an adjusted hazard ratio related to induced hypokalemia of 1.99 (95% confidence interval, 0.88-4.49). Results of sensitivity analyses were comparable to the main analysis.

Conclusion: The hazard ratio for hypokalemia with the use of levetiracetam versus carbamazepine was statistically comparable. However, the potential association between levetiracetam use and hypokalemia cannot be ruled out given the elevated hazard ratios from the main and sensitivity analyses. Further studies may provide a more precise assessment of this association.

Background and objectives: Nirmatrelvir/ritonavir was administered orally to manage mild to moderate symptoms of COVID-19 in adult patients. The objectives of this study were to (i) evaluate the cost-effectiveness of prescribing nirmatrelvir/ritonavir within 5 days of a COVID-19 illness in order to avert hospitalization within a 30-day period in the Malaysia setting; (ii) determine how variations in pricing and hospitalization rates will affect the cost-effectiveness of nirmatrelvir/ritonavir.

Methods: The 30-day hospitalization related to COVID-19 was determined using 1 to 1 propensity score-matched real-world data in Malaysia from 14 July 2022 to 14 November 2022. To determine the total per-person costs related to COVID-19, we added the cost of drug (nirmatrelvir/ritonavir or control), clinic visits and inpatient care. Incremental cost-effectiveness ratio (ICER) per hospitalization averted was calculated.

Results: Our cohort included 31,487 patients. The rate of hospitalization within 30 days was found to be 0.35% for the group treated with nirmatrelvir/ritonavir, and 0.52% for the control group. The nirmatrelvir/ritonavir group cost an additional MYR 1,625.72 (USD 358.88) per patient. This treatment also resulted in a reduction of 0.17% risk for hospitalization, which corresponded to an ICER of MYR 946,801.26 (USD 209,006.90) per hospitalization averted.

Conclusion: In Malaysia, where vaccination rates were high, nirmatrelvir/ritonavir has been shown to be beneficial in the outpatient treatment of adults with COVID-19 who have risk factors; however, it was only marginally cost effective against hospitalization for healthy adults during the Omicron period.

Background and objective: Iron deficiency is the most common cause of anemia. We compared the effect of ferric carboxymaltose (FCM), low-dose intravenous (IV) iron (LDI), and iron sucrose on total cost of care in patients with iron-deficiency anemia (IDA) from a US health plan perspective.

Methods: We conducted a retrospective claims analysis using the IQVIA PharMetrics Plus database. Patients with index (first) claims of FCM and LDI and a medical claim associated with IDA between 1 January 2017 and 31 December 2019 were included. Monthly total healthcare and inpatient and outpatient costs after receiving index IV iron for patients in the treatment cohorts were compared using a generalized linear model with gamma distribution and log-link.

Results: The overall study cohort included 37,655 FCM, 44,237 LDI, and 27,461 iron sucrose patients. Mean per-patient-per-month numbers of IV iron infusions for FCM, LDI, and iron sucrose were 0.20, 0.34, and 0.37, respectively. Compared with baseline, the FCM group had greater reductions in the number of hospital admissions and smaller increases in the number of outpatient visits in the 12 months post-IV iron therapy than LDI and iron sucrose, translating to significantly lower total healthcare cost (post-index adjusted cost ratio for total cost: 0.96 and 0.92, respectively; both P < 0.0001).

Conclusions: Higher drug acquisition cost of FCM relative to LDI and iron sucrose was offset by significantly lower inpatient and outpatient costs in the 12 months post-IV iron therapy. These results support the economic value of FCM for patients with IDA receiving IV iron therapy.

Introduction: A new algorithm for causality assessment of drugs and fatal cerebral haemorrhage (ACAD-FCH) was published in 2021. However, its use in clinical practice has not been verified.

Objectives: This study aimed to explore the practical value of the ACAD-FCH when applying information available in clinical practice.

Methods: The medical records of patients who died at the University of Tokyo Hospital in 2020 were reviewed, and cases with intracranial haemorrhage were selected. Two evaluators independently assessed these cases using three methods (the ACAD-FCH, Naranjo algorithm, and WHO-UMC scale). The number of 'Yes', 'No', and 'No information/Do not know' responses to each question by both evaluators were summed and compared. Inter-rater reliability was evaluated for each method using agreement rates and kappa coefficients with 95% confidence intervals (CI).

Results: Among 316 deaths, 24 cases with intracranial haemorrhage were evaluated. The proportion of ‛No information/Do not know' responses for each question was 35.6% (95% CI 31.4-40.6%) for the ACAD-FCH and 66.9% (95% CI 62.5-71.1%) for the Naranjo algorithm. The respective agreement rates and kappa coefficients were 0.917 (0.798-1.00) and 0.867 (0.675-1.00) for the ACAD-FCH, 0.708 (0.512-0.904) and 0.139 (-0.236 to 0.513) for the Naranjo algorithm, and 0.50 (0.284-0.716) and 0.326 (0.110-0.541) for the WHO-UMC scale, respectively.

Conclusion: Our findings suggest the utility of the ACAD-FCH when assessing death cases with intracranial haemorrhage. However, larger studies including intra-rater assessments are warranted for further validation of this algorithm.

Background and objectives: Clozapine shows higher efficacy against treatment-resistant schizophrenia than other antipsychotics. This study aimed to investigate whether clozapine is associated with the risk of non-hematological malignant tumors, utilizing the US Food and Drug Administration (FDA) Adverse Event Report System (FAERS) database.

Methods: The records from the first quarter of 2004 to the third quarter of 2012 were used for disproportionality analysis, and patients who developed non-hematological malignant tumors were identified by the Standardized Medical Dictionary for Regulatory Activities Queries (SMQ).

Results: Of the 3,641,281 patients with 12,401,586 reports of adverse drug events, 151,904 reports belonged to non-hematological malignant tumors (SMQ). We identified 1668 reports of non-hematological malignant tumors (SMQ) in clozapine users, and the reporting odds ratio (ROR) was calculated to be 1.28 (95% confidence interval (CI): 1.22-1.34). ROR (95% CI) for the relationship between clozapine and the risk of testis cancer was calculated as 10.94 (6.99-17.12), 9.87 (7.42-13.15) for gastrointestinal carcinoma, 7.48 (5.57-10.05) for metastatic lung cancer, 6.71 (4.52-9.97) for throat cancer, 6.12 (4.56-8.21) for metastases to the spine, 5.97 (5.30-6.72) for lung malignant neoplasm, 5.07 (3.69-6.95) for esophageal carcinoma, 1.88 (1.43-2.47) for colon cancer, and 1.65 (1.24-2.21) for metastases to the liver. Colon cancer, esophageal carcinoma, and throat cancer were predominantly reported in males, and metastases to the spine and liver were in females.

Conclusion: This study detected signals indicating a relationship between clozapine and certain non-hematological malignant tumors, utilizing the FAERS database. Despite the database relying on spontaneous reporting, the current results justify further investigation.