Journal of Drug Assessment最新文献

Background: As the human immunodeficiency virus (HIV) treatment landscape continues to evolve, the prolonged life expectancy and long-term exposure to antiretroviral drugs have modified the burden associated with living with HIV.

Objective: To better understand the current treatment and comorbidity burden in people living with HIV (PLWH).

Methods: Peer-reviewed systematic literature reviews (SLRs) between 2017 and 2020 that included US studies and examined drug adherence/pill burden, resistance burden, or comorbidities in PLWH were identified. Methods and findings were extracted for the overall studies and examined in the subset of US studies.

Results: Among 665 publications identified, 47 met the inclusion criteria (drug adherence/pill burden: 5; resistance: 3; comorbidities: 40). While antiretroviral drug adherence levels varied across SLRs, single-tablet regimens (STR) were associated with higher adherence versus multiple-tablet regimens. STRs were also associated with lower risk of treatment discontinuation, higher cost-effectiveness, and lower risk of hospitalization. Longer survival resulted in a high comorbidity burden, with non-AIDS causes accounting for 47% of deaths among PLWH in the US. HIV doubled the risk of cardiovascular disease and was associated with other health problems, including bone and muscle diseases, depression, and cancers. Several antiretroviral regimens were associated with chronic diseases, including cardiometabolic conditions. Lifetime HIV costs are substantially increasing, driven by antiretroviral, adverse event, and comorbidity treatment costs cumulated due to longer survival times.

Conclusions: There is a considerable burden associated with HIV and antiretroviral treatment, highlighting the benefits of less complex and safer regimens, and the unmet need for effective preventative interventions.

Purpose: Discovery of falsified Symbicort 320/9 Turbohaler identified in the UK in 2013 demonstrated that falsified dry powder inhalers were also present in the European market. This work aimed to investigate the current situation of formoterol-containing dry powder inhalers in Europe and North Africa by assessing their aerodynamic performance profile.

Methods: A total of eight registered formoterol-based dry powder inhalers over the European and North African markets were involved in this study, including the reference drug Foradil. Samples were prepared using a multistage liquid impinger (MsLI) and further analyzed by a validated HPLC-UV method to determine the delivered and the fine particle doses (FPDs). This study also examined the impact of freezing-thawing cycles on sample stability in terms of analytical purpose handling.

Results: No substandard dry powder inhalers were identified among the medicinal products involved in this work. The delivered dose (DD) of assessed drugs varied from 8.33 to 9.69 µg, while the FPD was between 1.86 and 3.35 µg. As expected, this work confirmed that the capsule composition and the barrier properties of the primary packaging can affect the FPD of dry powder for inhalation use.

Conclusions: The FPD of products C and B was, respectively, 17.4 and 14.2% superior to Foradil, products D and H had the closest values compared to the original drug, and product F was 34.5% inferior. Additionally, this work showed that a high FPD can be achieved using HPMC capsules and moisture-impermeable primary packaging.

Objective: To understand current treatment patterns and health care resource utilization (HRU) of women with locally advanced or metastatic breast cancer (advanced breast cancer; ABC) in Korea overall and within patients who had progressed with prior endocrine therapy (as first-line treatment for metastatic disease) and patients with no prior systemic treatment (for advanced disease).

Methods: A chart review was conducted in 109 patients (women ≥ 18 years old with HR+/HER2- ABC diagnosed between 2015 and 2017) from 11 hospitals. Anonymized data on patient characteristics, treatment patterns and HRU was abstracted.

Results: Mean (range) age of all patients was 57.5 (40-81) years. Overall, the most common first-, second- and third-line systemic therapy after diagnosis of ABC were letrozole ± palbociclib (51%), endocrine therapy (ET)±everolimus (42%) or chemotherapy (ChT) (39%), and ChT (68%), respectively. In patients progressed with ET (n = 33) and those with no prior systemic treatment (n = 52), the most common first-line treatments were letrozole (82%) and letrozole + palbociclib (42%), respectively. The percentage of patients with at least one grade 3 or higher adverse event during first-line therapy was 93.1% vs 39.2% in patients on a ChT based regimen (N = 29) vs. ET (N = 74). Overall, oncologist visits, at an annual rate of 9.27 (95% CI: 8.87, 9.69) visits per month, and hospitalizations, with an annual rate of 0.44 (95% CI: 0.36, 0.54), and mean (SD) length of stay of 14.3 (10.32) days, were the key drivers of HRU.

Conclusions: These findings on real world HRU reflected clinical guidelines and severity of ABC. Results can inform future evaluations of new ABC treatments that estimate the health economic impact of their adoption in Korea.

A common chemotherapy regimen in post-transplant lymphoproliferative disease (PTLD) following solid organ transplants (SOT) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). This study reviews the quantitative evidence for long-term consequences associated with components of CHOP identified from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cited references were screened using prespecified criteria (English, systematic review, randomized controlled trial n > 100, observation study n > 100, case series n > 20). Relevant data were extracted and synthesized. Of 61 studies, 66% were retrospective cohort studies, 28% were in the US, and 95% enrolled pediatric patients. No study focused specifically on the CHOP regimen. Long-term consequences for CHOP components observed in >3 studies included cardiac toxicity (n = 14), hormone deficiencies/infertility (n = 14), secondary leukemia (n = 7), osteonecrosis (n = 6), and bladder cancer (n = 4). These effects are significant, impact a high percentage of patients, and occur as early as one year after treatment. Although none of the studies focused specifically on the CHOP regimen, 30%, 23%, and 15% evaluated alkylating agents (e.g. cyclophosphamide), anthracyclines (e.g. doxorubicin), and corticosteroids (e.g. prednisone), respectively. All three product classes had a dose-dependent risk of long-term consequences with up to 13.2-fold, 27-fold, 16-fold, 14.5-fold, and 6.2-fold increase in risk of heart failure, early menopause, secondary leukemia, bladder cancer, and osteonecrosis, respectively. Lymphoma patients had significantly elevated risks of cardiac toxicity (up to 12.2-fold), ovarian failure (up to 3.8-fold), and osteonecrosis (up to 6.7-fold). No studies were found in PTLD or SOT. Safe and effective PTLD treatments that potentially avoid these long-term consequences are urgently needed.

Objective: Pivotal clinical trials revealed good clinical efficiency of ocrelizumab while having a good safety profile in the management of multiple sclerosis (MS). However, real-world data of ocrelizumab in daily clinical practice remain scarce. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for MS in an Arab population in a real-world clinical setting.

Methods: In this retrospective single-center observational study in Qatar, we reviewed the medical records and analyzed the clinical and MRI data of all patients with relapsing-remitting MS (RRMS) and active secondary progressive MS (aSPMS)-between October 2017 through December 2020-who had received at least one infusion of ocrelizumab (Q-OCRE).

Results: A total of 60 MS patients were included (57 with RRMS, three SPMS). The Median follow-up period was 19 months (range, 1-32). The most common reason for switching to ocrelizumab was increased disease activity and three-quarters of the patients were on a previous disease-modifying drug (DMD). No evidence of disease activity (NEDA) status at year 1 was achieved in 73% of the cohort. Mild infusion-related reactions (IRR) and infections were reported (mainly upper respiratory tract infections followed by urinary tract infection) with a declining percentage over the follow-up applications. No severe side effects were observed.

Conclusion: Our real-world experience confirms good efficacy, tolerability, and safety of ocrelizumab in our Arab population.

Objective: Receptor activator of NF-κβ ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with Denosumab could improve fasting plasma glucose (FPG) and insulin (FPI).

Methods: A systematic review was conducted to evaluate the effects of Denosumab on glycemic parameters. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of Denosumab on FPG, glycated hemoglobin (HbA1c), FPI, and Homeostatic Model Assessment for Insulin Resistance (HOMA1-IR). The pooled standard difference in means (SDM) and 95% confidence intervals (95%CI) were calculated. The results were stratified into (1) Normal Glucose Tolerance (NGT) and (2) Impaired Glucose Tolerance (IGT).

Results: Six publications (1203 participants) were included. There was a significant association between Denosumab and FPG (SDM = -0.388, 95%CI: -0.705 to -0.070, p = .017) and with HOMA1-IR (SDM = -0.223, 95%CI: -0.388 to -0.058, p = .008), but not for HbA1c and FPI. When stratified by glucose tolerance, the association between Denosumab and FPG, HbA1c, and HOMA1-IR was present for the IGT group. Lastly, Denosumab had a time-dependent effect on HbA1c (slope = -0.037, 95%CI: -0.059 to -0.015, p < .005).

Conclusions: Denosumab significantly improved glycemic parameters. This outcome was more prominent for subjects with compromised glucose tolerance, positing that Denosumab can be used as a treatment to improve glucose metabolism for persons with pre-diabetes and diabetes.

Objective: This study aimed to compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination(Cosopt) in newly diagnosed primary open-angle glaucoma (POAG) patients.

Methods: In this prospective, interventional case series, newly POAG patients were included. Patients were started on Cosopt twice a day (BID) for one month and then switched to three times a day (TDS) for an additional month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP), and 24-h heart rate (HR) measurements at baseline, month 1(BID), and month 2(TDS). Throughout the study, all adverse events were monitored by the investigators.

Results: In 31 POAG patients that completed the study, the mean baseline IOP was 23.1 ± 3.15 mmHg. IOP was decreased significantly 16.5 ± 2.21 at one month (p < .0001) and 13.9 ± 2.23 mmHg at 1 and 2 months follow up (p < .0001). IOP was significantly lower in month 2 compared to month 1 (p = .0004). While Cosopt BID significantly reduced the mean 24-h systolic BP and mean 24-h HR from baseline (p < .0001), the mean 24-h systolic BP and HR remained unchanged with Cosopt TDS compared to BID (p = .62).

Conclusions: Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profiles.

Acute repetitive seizures, also called seizure clusters, are common phenomena in patients with epilepsy. They are a burden on patients and their caregivers and may be very disruptive to the patients' lives. They may progress to prolonged seizures or status epilepticus if they are not aborted as soon as possible. However, their definition, recognition, and classification still suffer from a lack of consensus among healthcare professionals in the field. This review aims to shed light on various aspects of seizure clusters with particular attention to their treatments.