Advances in Therapy最新文献

Introduction: The prescription of non-steroidal anti-inflammatory drugs (NSAIDs) covered by the Italian National Health Service is limited to certain pathologies defined in the 2018 update of Note 66 of the Italian Medicines Agency (AIFA), meant to ensure appropriate use of NSAIDs. This analysis was conducted in real clinical practice to describe NSAID utilization from 2019 to 2022 with respect to Note 66 update.

Methods: For this real-world analysis, data were extracted from the administrative databases of healthcare institutions covering ~ 9.1 million citizens. From 2019 to 2022, all subjects with ≥ 1 NSAID prescription were identified. Demographic and clinical characteristics, the proportion of NSAID-treated patients over time, the most prescribed molecules, and drug consumption defined as daily dose (DDD) per 1000 inhabitants/day were recorded.

Results: The percentage NSAID-treated patients showed a slight increase over time (1.9-3.0%). The most prescribed active ingredients were diclofenac, ketoprofen, nimesulide, etoricoxib, and ibuprofen. NSAID consumption increased from 15.5 to 16.8 DDD/1000 inhabitants/day over 2020-2022, especially in older patients (65-74 years group: 36.2-39.3 DDD/1000 inhabitants/day). From 2019 to 2022, 2,811,910 patients with NSAID prescription(s) in Note 66 were identified, whose average age was 59.7 years. Among them, 0.1-1.0% received NSAIDs for rheumatic diseases and 11.9% in the oncological setting. While diclofenac, etoricoxib, and ketoprofen were commonly prescribed at medium-low dosage as recommended, ibuprofen was used at high dosage (600 mg) in 80% of cases.

Conclusion: The analysis showed that patients prescribed with NSAIDs were relatively young (~ 60 years), in contrast with the pathologies covered by Note 66, which typically affect elderly people. Moreover, rheumatic and oncological diseases were poorly represented, thus it is possible that NSAIDs might have been prescribed for indications outside the note. These findings suggest that the use of NSAIDs for pain management in Italy should be optimized, properly weighting their risks and benefits.

Several complications can occur during laparoscopic gynecological surgery. The insertion of trocars and the induction of pneumoperitoneum are essential steps, but they can still pose potential risks during laparoscopic surgery. Bowel injuries are the most common during gynecological procedures as a result of thermal damage and trocar placement, while vessel injuries may carry a high mortality rate. Gynecologic surgeons should be aware of the risks associated with laparoscopic procedures and be able to prevent and treat potential complications. We conducted a literature search using three electronic databases (Pubmed/MEDLINE, Google Scholar, Embase) from inception to May 2024 to identify the most common intraoperative gynecological laparoscopic complications, including those related to trocar insertion, bowel, urinary, and vessel injury. The aim of this narrative review is to describe the most common complications during gynecological laparoscopic surgery and to outline the safety rules and techniques necessary for their prevention and treatment.

Introduction: Gonadotropin-releasing hormone (GnRH) agonist injection frequency does not affect prostate cancer treatment efficacy; however, it may influence treatment satisfaction, adherence, and overall healthcare utilization. This study addressed the limited information available on real-world patient experience with GnRH treatments by surveying a diverse population of patients with prostate cancer in Europe.

Methods: This noninterventional, cross-sectional study included adults with locally advanced or metastatic prostate cancer in Belgium, France, Italy, Spain, and the UK. Data were collected via a one-time self-administered electronic survey (October-December 2023) that assessed patient preferences for injection frequency, satisfaction, healthcare resource utilization, and involvement in treatment decision-making.

Results: Of 414 participants, 53.9% preferred a 6-month injection frequency, while 27.3% preferred a 3-month frequency. Among those receiving injections every 6 months, 77.0% were satisfied; 62.7% of those receiving injections every 3 months were satisfied. Two-thirds of participants (65.7%) were aware of different frequencies of injections. Among those who preferred a 3-month injection frequency, routine and perceived control over their disease were important factors, with 38.1% receiving injections at the same frequency as doctor visits. Among those preferring a 6-month frequency, convenience and routine were important; however, 7.2% indicated that their preference was based on a dislike or fear of injections. Of those with no preference, 60.3% indicated that this was because they deferred to their doctor's advice. Most patients required transport to their injection appointment, and of those who were employed, 79.2% required time off from work. Accompaniment to an injection appointment was also important, with 66.2% of patients never attending alone.

Conclusion: The high satisfaction rates, particularly among those receiving injections every 6 months, suggest that less-frequent injections may be more convenient and preferable for many patients. These insights can help to guide patient-centric care and treatment decisions in prostate cancer management.

Introduction: The INTEGRATE study aimed to provide information on the use, effectiveness, and safety of esketamine nasal spray (ESK-NS) for the treatment of treatment-resistant depression (TRD) in real-world practice in Spain.

Methods: This was an observational, cross-sectional, retrospective study conducted in adults aged 18-74 years who met the criteria for TRD. The weekly impact of ESK-NS on depressive symptoms was evaluated by clinical judgment using four categories (nonresponse, response, remission, not available). The onset of action 24 h after administration was also evaluated. Information on adverse events was collected from the medical records.

Results: We included 196 patients, of whom 189 were considered evaluable; the mean (SD) number of previous episodes was 3.7 (3.0). According to the investigator's judgment, 152 (80.4%) of 189 patients were in response or remission in the induction phase, and 54 (90%) of 60 during the maintenance phase. The proportions of patients in remission were 9.5%, 18.7%, and 38.3% during the induction, optimization, and maintenance phases, respectively. Fifty-three (28.0%) patients experienced an improvement in depressive symptoms within the first 24 h after the first administration of ESK-NS. Most adverse events reported with ESK-NS were mild and did not require any action with the study drug; the number of adverse events decreased over time, especially during the first 4 weeks.

Conclusion: Consistent with the available evidence, the results of this study indicate that ESK-NS is an effective and safe option to consider within the therapeutic algorithm for TRD.

The pituitary adenylate cyclase-activating peptide (PACAP) pathway is a critical focus in the pathophysiology of several headache disorders. PACAP influences headache pathophysiology through interactions with distinct receptors (PAC₁, VPAC₁, and VPAC₂) and pathways linked to neurovascular and hormonal regulation. Evidence supports its role in the modulation of trigeminal and parasympathetic systems, implicated in cluster headaches and menstrual migraine, and its involvement in sensitizing pain pathways post trauma in post-traumatic headaches. Early clinical trials targeting PACAP signaling show promise, with one study demonstrating efficacy in migraine prophylaxis. This narrative review synthesizes current evidence while addressing gaps in understanding PACAP's precise mechanisms. Future research should prioritize expanding the scope of PACAP-focused investigations across diverse headache types, aiming to establish it as a therapeutic target for several headache disorders. Success in ongoing and future trials could redefine headache management for millions of underserved patients worldwide.

Introduction: This study explored patient and clinician perspectives on a new fixed-dose combination of macitentan and tadalafil (M/T FDC) in a once-daily single tablet for treatment of pulmonary arterial hypertension (PAH).

Methods: Qualitative semi-structured interviews were conducted during the open-label period of the global, phase 3 A DUE clinical trial that evaluated M/T FDC. A subset of enrolled patients (N = 26) and site investigators (N = 18 clinicians) were interviewed. Patients received four tablets during double-blind treatment and could be in one of three arms (macitentan + placebo; tadalafil + placebo; M/T FDC + placebo) followed by M/T FDC (one tablet) during the open-label period. Patients and clinicians were asked to share their experience of pre-trial PAH medication, double-blind treatment, and open-label M/T FDC. Thematic analysis was conducted on blinded data.

Results: Patients preferred the M/T FDC tablet (open-label) over the four tablets during double-blind treatment. Patients were satisfied with M/T FDC, highlighting its positive impact on their psychological well-being, through reducing stress associated with managing multiple pills. All patients indicated that having a single, once-a-day pill for PAH was more convenient and associated with greater treatment adherence. Clinicians highlighted that their patients have a high daily pill burden for PAH and other comorbidities, and prefer treatments with an oral mode of administration that reduce the number of daily pills required. Clinicians felt that M/T FDC would be well received in clinical practice and potentially assist in implementing guideline-recommended combination treatment of PAH.

Conclusions: In this qualitative analysis, all 26 patients and 18 clinicians provided positive feedback on M/T FDC treatment, which was consistent across countries. Reducing the number of pills needed to treat PAH, through use of single-tablet M/T FDC, is highly valued by patients and endorsed by clinicians, who both felt the single-tablet combination therapy could have a positive effect on patients' well-being and increase treatment adherence.

Introduction: The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against the use of programmed cell death protein-1 inhibitors for first-line treatment of advanced or metastatic unresectable esophageal squamous cell carcinoma (ESCC) with a programmed death-ligand 1 (PD-L1) expression Tumor Area Positivity (TAP) score < 1% or combined positive score < 1 due to an unfavorable benefit-risk profile observed across the phase 3 CheckMate 648, KEYNOTE-590, and RATIONALE-306 trials. Therefore, we conducted a retrospective analysis of RATIONALE-306 to evaluate the efficacy and safety of tislelizumab plus investigator-chosen chemotherapy (ICC) versus placebo plus ICC in patients with advanced or metastatic unresectable ESCC and a PD-L1 TAP score ≥ 1%.

Methods: Adult patients with advanced or metastatic unresectable ESCC enrolled in the global, randomized, phase 3 RATIONALE-306 trial randomly received tislelizumab 200 mg every 3 weeks plus ICC or matched placebo plus ICC. Efficacy and safety outcomes were evaluated among patients who were retrospectively assessed for PD-L1 expression defined by a TAP score ≥ 1%.

Results: At primary analysis data cutoff (February 28, 2022), a clinically meaningful improvement in median overall survival was observed among 230 patients in the tislelizumab plus ICC arm {16.8 [95% confidence interval (CI) 15.3-20.8] months} versus 248 patients in the placebo plus ICC arm [9.6 (95% CI 8.9-11.8) months] [stratified hazard ratio 0.64 (95% CI 0.51-0.80)]; this was maintained at a 3-year follow-up data cutoff (November 24, 2023). Similar findings at primary analysis were observed for progression-free survival, objective response rate, disease control rate, and duration of response. Tislelizumab plus ICC was tolerable and no new safety signals were observed.

Conclusions: Tislelizumab plus ICC is an effective and well tolerated first-line treatment option for patients with advanced or metastatic unresectable ESCC and a tumor PD-L1 TAP score ≥ 1%.

Trial registration number: ClinicalTrials.gov NCT03783442.

Introduction: This study aimed to explore the beneficial effect of a preservative-free (PF) emulsion eyedrop combining high molecular weight sodium hyaluronate (HMW-HA) and alpha-lipoic acid on oxidative stress and ocular surface inflammation in patients with dry eye disease (DED).

Methods: In this prospective exploratory study, patients with moderate to severe DED symptoms were treated with the study eyedrop, 4-6 times/day for 1 month. Two visits were scheduled: baseline (D0) and after 35 days (D35). The following parameters were assessed: quality of life (OSDI score); superoxide dismutase (SODase) concentration in tears; goblet cell (GC) density (impression cytology); conjunctival hyperemia (Efron scale); corneal, conjunctival, and eyelid staining (Oxford scale); and meibomian gland (MG) blockage. Data were compared between D0 and D35 in subgroups of patients with a significant abnormality of the study outcome at baseline.

Results: Forty patients were involved, with a highly significant improvement of OSDI score at D35. The mean concentration of SODase significantly increased by 3.2 and 2.4 times for SODase1 and SODase2 respectively, in patients with deficient SODase at baseline. In patients with abnormal GC density at baseline, GC count increased by five times at D35. Conjunctival hyperemia and corneal staining scores significantly improved in the subpopulation of patients with a baseline grade ≥ 2. Eyelid margin staining was significantly reduced at D35 in patients with significant abnormalities at baseline. A significant reduction of MG obstruction was shown in the lower eyelid in patients with significant blockage at baseline.

Conclusion: The use of a PF ophthalmic emulsion combining alpha-lipoic acid and HMW-HA shows a beneficial effect on the ocular surface through the improved quality of life score. Noteworthy, patients presenting high oxidative and inflammatory conditions experienced significant improvement in oxidative stress and inflammation markers; this synergic effect is likely due to the well-known properties of alpha-lipoic acid and HMW-HA, enhancing DED management.

Trial registration: ISRCTN.com identifier, 17861788.

Introduction: The increased risk of falls in elderly people represents a substantial public health burden that may be compounded by impaired visual acuity. The present study aimed to assess the independent risk of incident falls and fractures in patients with geographic atrophy (GA).

Methods: This retrospective, noninterventional, cohort study analyzed three US claims datasets (Optum's de-identified Clinformatics^® Data Mart Database [Clinformatics^®], Merative™ MarketScan^® Commercial and Medicare Databases [MarketScan], and IQVIA US PharMetrics^® [PharMetrics]). Patients were defined as having at least one International Classification of Diseases, Tenth Revision code (H35.31x3, H35.31x4) for GA. A propensity score-matched control cohort, matched on age, sex, index year, and disease history, was also included. Relative risks (RRs) for incident falls, fractures, and health care resource utilization (HCRU) were calculated between GA and control cohorts.

Results: The Clinformatics^®, MarketScan, and PharMetrics datasets included 44,591, 9470, and 27,428 patients with GA, respectively. Across the three databases, mean (SD) age ranged from 75.9 (8.3) to 80.5 (7.2) years, and 61% to 64% were female. The largest subgroup was patients with bilateral GA without subfoveal involvement (35-37%), followed by unilateral GA without subfoveal involvement (23-24%). Risks of falls (RR 1.16-1.36) and fractures (RR 1.17-1.29) in the 4 years following the index date were higher in patients with GA compared with controls. Patients with bilateral GA and subfoveal involvement had the most pronounced increase in risk of falls (RR 1.42-1.49) and fractures (RR 1.33-1.45). Compared to controls, patients with GA also had an increased risk for hospitalization (RR 1.18-1.27), emergency department visits (RR 1.18-1.21), nursing home or assisted living admissions (RR 1.06-1.28), and outpatient visits (RR 1.05-1.08).

Conclusion: GA represents an independent risk factor for falls, fractures, and higher HCRU. These data reveal the substantial public health burden of GA associated with the management of falls and fractures.

Introduction: Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score < 1 or TAP score < 1%, due to an unfavorable benefit-risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%.

Methods: Adult patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC were randomized to tislelizumab 200 mg or placebo with ICC every 3 weeks. Efficacy and safety outcomes of tislelizumab plus ICC versus placebo plus ICC were retrospectively assessed in those with a PD-L1 TAP score ≥ 1%.

Results: At the final analysis cutoff (February 28, 2023), 432 patients received tislelizumab plus ICC and 453 received placebo plus ICC, and had a PD-L1 TAP score ≥ 1%. Clinically meaningful improvements to OS were observed with tislelizumab plus ICC compared with placebo plus ICC [15.0 months (95% confidence interval [CI] 13.3-16.7) vs. 12.8 months (95% CI 12.1-14.1), respectively; stratified hazard ratio 0.77 (95% CI 0.67-0.90)]. Progression-free survival, overall response rate, duration of response, and disease control rate, were also improved. OS improvements were maintained at a 3-year data cutoff (February 28, 2024). Tislelizumab plus ICC had an acceptable safety profile with no new safety signals.

Conclusions: Tislelizumab plus ICC is an effective and tolerable first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC with a PD-L1 TAP score ≥ 1%.

Trial registration number: NCT03777657.