Journal of Drug Assessment最新文献

Atopic Dermatitis (AD) is a chronic inflammatory disease persisting predominantly in the pediatric population. Treatment is generally supervised by various medical specialists, including primary care practitioners, allergists, and dermatologists. This divergence in disease management allows various therapeutic approaches to be administered to patients by supervised physicians. This article covers etiology of the disease and summarizes dermatologic treatment standards of selected countries binding prior to the registration of dupilumab by both the European Medicines Agency (EMA) and Federal Drug Administration (FDA) in 2017. Before recent development in targeted therapies (small molecules and biologic agents), standards in AD treatment remained unchanged for years with extensive similarities across a sample group of countries in particular geographic and economic regions. The spectrum of available and popular therapeutic options can be categorized into three dominating groups: non-pharmacologic, pharmacologic, and systemic interventions. Their prescription, in principle, was historically driven by disease severity and previous treatment history. However, advances in targeted therapies may change AD management guidelines and medical care standards.

Objective: Long-term safety and efficacy of 10- and 20-mg rupatadine in Japanese patients with perennial allergic rhinitis (PAR) were investigated in a 52-week open-label study (JapicCTI-152952, clinicaltrials.jp). Methods: The rupatadine dose was fixed to 10 mg once daily for the first 2 weeks. Thereafter, the study investigator was allowed to increase the dosage to 20 mg if the response was insufficient. Safety was evaluated on the basis of treatment-emergent adverse events, laboratory findings, and vital sign measurements. The primary efficacy endpoint was changed from baseline to Week 2 in the total 4 nasal symptom score. Secondary efficacy endpoints included changes over time in ocular symptoms, patient and physician clinical overall impression, and patient quality-of-life. Results: Seventy-two immunoglobulin E positive patients (mean age = 32.1 years), consisting of 58 adults (age ≥ 18 years) and 14 adolescents (12-17 years), were enrolled. Ninety-four treatment-emergent adverse events were reported in 48 patients (66.7%), including nine adverse drug reactions in nine patients (12.5%). The most frequently reported adverse drug reaction was somnolence (9.7%). The primary and secondary efficacy endpoints demonstrated a statistically significant clinical benefit with rupatadine. The rupatadine dose was increased from 10 to 20 mg in 36 patients (50.0%), which resulted in better symptom management. Conclusions: Rupatadine 10- and 20-mg once-daily doses were well tolerated in long-term use. Updosing to 20 mg is a reasonable option in PAR patients whose symptoms cannot be controlled effectively by the 10-mg dose.

Background: The incidence of Type 2 Diabetes Mellitus (T2DM) in Egypt is considered one of the highest in the world. Metformin and Sulfonylureas are usually prescribed together due to their efficacy and their relatively low cost. Organic cation transport 1, encoded by SLC22A1 gene, is the main transporter of metformin into hepatocytes, which is considered metformin site of action. Sulfonylureas enhance insulin release from pancreatic B-cells through binding to sulfonylurea receptor 1, encoded by ABCC8 gene. Single nucleotide polymorphisms in the SLC22A1 and ABCC8 genes might affect the response of each drug. Aims: To investigate the influence of SLC22A1 rs622342 (A>C) and ABCC8 rs757110 (A>C) genetic variants on the efficacy of metformin and glimepiride combination therapy in Egyptian T2DM patients. Methods: Observational cross-sectional study in which patients receiving metformin and glimepiride combination therapy for at least 6 months were included for genotyping and classified into either responders or non-responders, based on their HbA1C level. Results: A total of 127 patients were included and genotyped. They were divided into 93 responders (HbA1C<7%) and 34 non-responders (HbA1C≥7%). Minor allele frequencies for rs622342 and rs757110 were 0.189 and 0.271, respectively. Only SLC22A1 rs622342 variant was found to be associated with the response of combination therapy, in which AA alleles carriers were 2.7-times more responsive to metformin than C allele carriers (Recessive model, odds ratio = 2.718, p = 0.025, 95% CI = 1.112-6.385). Conclusion: Genotyping of rs622342 can be useful in predicting the response to metformin in combination therapy in Egyptian T2DM patients.

Objective: This study was conducted to determine the incremental healthcare resource utilization (HRU) and costs associated with relapse or recurrence (R/R) in patients with major depressive disorder (MDD) treated with antidepressants (AD) in US clinical practice. Methods: In this retrospective cohort study, adult patients with MDD treated with a branded AD were selected from the Truven Health Analytics MarketScan Databases (January 1, 2004-March 31, 2015). Time to first indicator of R/R was described. Characteristics, HRU, and costs were compared between patients with and without R/R. Among patients with R/R, HRU and costs were also compared between the pre- and post-R/R period. Results: From the 22,236 selected patients, 5,541 had ≥ 1 indicator of R/R and 16,695 did not. The 3-year R/R rate varied between 21.3% and 36.4% based on pattern of AD use (continuous, switch/augmentation, or early discontinuation). Patients with and without R/R presented different characteristics-notably, more intensive prior AD use and a higher comorbidity burden. HRU and costs were high in both patients with and without R/R but substantially higher among those with R/R ($20,590 vs $12,368 per-patient-per-year (PPPY); adjusted difference [aDiff] = $7,037), mainly driven by increased inpatient (IP) services (adjusted incidence rate ratio IP days = 3.95; aDiff IP costs = $3,433 PPPY). Among patients with R/R, emergency department visits, IP days, and IP admissions were over 2-times higher during the post-R/R period and total costs increased by over 50% from $19,267 to $29,419 in the post-R/R period. Conclusions: The economic burden in MDD patients is substantial, but is significantly higher among those who experience R/R.

Purpose: The objective of this pilot study was to explore the feasibility of conducting a drug utilization study of lipegfilgrastim in Europe using medical records and to examine the pattern of lipegfilgrastim on-label and off-label use. Methods: Data on lipegfilgrastim use between September 2014 and April 2017 were abstracted from medical records by two independent medical abstractors. Lipegfilgrastim indication was categorized either as on-label or as one of four types of off-label (I-IV) according to pre-defined criteria. An inter-rater reliability analysis was conducted to measure the degree of abstractor agreement for on-label and off-label use. Results: Information from 46 medical records was abstracted. Lipegfilgrastim use during the first chemotherapy treatment cycle was mostly indicated for prevention of neutropenia (82.6% of patients). On-label use was documented in 42 patients (91.3%), while off-label use was documented in two patients (4.3%); all events of off-label use were attributed to use with non-cytotoxic drugs. The remaining two patients (4.3%) had missing data. Overall agreement between the abstractors was high (91.6%). For three types (Types I-III) of off-label use, the kappa values suggested a perfect agreement (κ = 1). For Type IV off-label use (use in patients treated with non-cytotoxic drugs), κ = 0, suggesting a poor agreement. Conclusions: While recruitment was challenging, the results of this pilot study confirm the feasibility and availability of medical records and the use of pharmacists as abstractors to assess on- and off-label use of lipegfilgrastim. Lipegfilgrastim was mainly prescribed according to the approved indications.Key pointsFindings from this pilot study confirm the feasibility and availability of medical records and the use of pharmacists as abstractors to assess on-label and off-label use of lipegfilgrastim in routine clinical practice.Lipegfilgrastim was mainly prescribed according to the approved indications, and the proportion of off-label use was low.The high inter-rater agreement between the two abstractors suggests that one abstractor is sufficient for conducting chart abstraction of on- and off-label use.Additional data abstraction sources other than pharmacists will need to be identified to improve response rate and center recruitment.Findings from this pilot study are important for the successful planning and execution of subsequent drug utilization studies.

Objective: The purpose of this study was to determine the efficacy of Extracorporeal Shock Wave Therapy (ESWT) in combination with the dietary supplement Tendisulfur Forte in the treatment of shoulder tendinopathy, lateral epicondylitis, and Achilles tendinopathy. Methods: Patients were sub-divided for each pathology into two equal sized groups of 15: one treated with ESWT supplemented with Tendisulfur Forte, and the other treated with ESWT only. Shoulder functionality was measured through the UCLA shoulder score. Treatment of epicondylitis was assessed with the Mayo elbow score. Achilles tendinopathy was measured with the VISA-A score. Pain through the various groups of the study was measures with the Visual Analog Scale (VAS). Results: Patients in the Tendisulfur Forte group had overall better functional and VAS scale scores for shoulder tendinopathy, elbow epicondylitis, and Achilles tendinopathy. UCLA scores for shoulder tendinopathy showed significant results at 60 days in the Tendisulfur Forte group (p = 0.0002). Mayo scores in the treatment of lateral epicondylitis was significant at 60 days in the study group (p < 0.0001). Achilles tendinopathy was improved in the study group at 30 days (p < 0.0001). VAS scales were significant for each pathology at 60 days (p < 0.0001). In addition, NSAIDs consumption was greatly reduced and, in most cases, stopped in the Tendisulfur Forte Groups. Conclusion: Concerning the results obtained, this paper underlines the effectiveness of combined treatment of ESWT plus Tendisulfur Forte, in the absence of side-effects. Indeed, oral supplementation lead to a faster recovery and better outcomes with a significant reduction in NSAIDs consumption.

Context: In Italy, little is known about the territorial distribution of the frailty status. Aims: To compare frailty- and multimorbidity-prevalence in the elderly population of two Italian regions. Methods: This study examined randomized samples of elderly (both community dwelling and institutionalized) assisted by general practitioners. Frailty was evaluated through the CSHA-Scale, multimorbidity through the Charlson-Score. The relation between frailty and multimorbidity was studied through a logistic model. Both crude and standardized prevalences were calculated. Results: One hundred and sixteen physicians assisted 176,503 patients highly representative of Italian people. In a randomized sample of 4,531 older people, the sex-age-standardized prevalence of Frailty (standard population: Italy) was 25.74% (24.63-26.85%). Age-standardized prevalence for males was 20.08% (18.46-21.71%) and 30.00% (28.54-31.57%) for females. Using the sex-age-standardization pooled sample, the prevalence of frailty was significantly higher in Sicily than Veneto (28.74% [27.03-30.46%] vs 22.30% [20.94-23.67%]. This study did not find differences in the prevalence of multimorbidity: Veneto 20.76% (19.21-22.31%); Sicily 22.05% (20.33-23.77%). Both "to be female" and "to live in Sicily" were shown to be predictors of frailty OR for being female = 1.64 (1.42-1.88); OR for living in Sicily = 1.27 (1.11-1.46). Multimorbidity was an independent frailty-predictor only for those aged < 85: OR of Charlson Index ≥ 4 for ages < 85 = 3.44 (2.88-4.11), OR for ages ≥ 85 = 1.44 (0.97-2.12). Limitations: (1) This study considered patients assisted by doctors, not a random sample of the general population. (2) The cross-sectional nature of the study limits the interpretation of the relationships between frailty and multi-morbidity. (3) Few covariates were available for our multivariate models. Conclusions: More than 1/4 of elderly persons are shown to be frail (1/5 of males and 1/3 of females). Frailty is more frequent in Sicily, while multimorbidity does not differ between the two regions. This could be due to regional differences in the organization of care networks dedicated to elderly patients.

Background: Clinical practice guidelines for the treatment of idiopathic pulmonary fibrosis (IPF) currently recommend pirfenidone and nintedanib. However, there is a lack of evidence from head-to-head comparisons. Objectives: To perform a systematic review and network meta-analysis (NMA) to access the efficacy and tolerability of two new treatments for IPF, pirfenidone and nintedanib. Methods: Randomized controlled trials (RCTs) selection (CENTRAL, MEDLINE, Embase), data extraction, risk of bias analysis, and GRADE assessment were carried out by two authors separately. Direct estimates were calculated using standard pairwise meta-analysis. A Bayesian mixed treatment comparison approach for NMA estimates, with 95% confidence intervals (CI), was used to compare the treatments, calculating odds ratios (OR) and number needed to treat (NNTB) or harm (NNTH). Results: The NMA on 10 randomized controlled trials showed that each drug had a positive effect on percentage of forced vital capacity (FVC) decline ≥ 10% (pirfenidone OR = 0.54 [95% CI = 0.37-0.80], NNTB = 9 [95% CI = 7-22]; nintedanib OR = 0.59 [95% CI = 0.41-0.84], NNTB = 9 [95% CI = 6-23]), but no significant differences were noted when comparing pirfenidone and nintedanib with respect to acute exacerbations, mortality, and serious adverse events (FVC decline OR = 0.91 [95% CI = 0.45-2.03]) or dropouts (OR = 0.75 [95% CI = 0.33-1.27]). Nintedanib showed an effect on dropouts, OR = 1.61 (1.13-2.28) and NNTH = 14 (8-61). Conclusions: Based on RCTs of 12 month duration in patients with IPF, a positive effect on FVC decline was noted for both treatments and on dropouts for nintedanib, but no significant differences were noted between treatments.

Background: Patients with acute peripheral arterial occlusion (aPAO) are candidates for operative thrombectomy, bypass, or catheter-directed thrombolysis (CDT) using a plasminogen activator. Human plasma-derived plasmin may offer another CDT option. Objectives: To evaluate the efficacy, safety, and tolerability of two intrathrombus delivery methods and two doses of plasmin compared with recombinant tissue plasminogen activator (rtPA) and placebo in patients with aPAO. Patients/methods: This was a phase 2, randomized, open-label study of intra-arterial CDT of plasmin in patients with aPAO. The study used infusion catheters with or without balloon occlusion (BOC) to evaluate 150 mg plasmin (2 and 5 h post-infusion) and 250 mg plasmin (5 h post-infusion). The efficacy of plasmin, rtPA and placebo was assessed. Results: One hundred and seventy-four subjects were enrolled. Overall, the thrombolytic efficacy (>50% thrombolysis) was 59% (58/99) for 150 mg plasmin without BOC, which is comparable to 89% (8/9) for rtPA without BOC (p = 0.149) and 40% (2/5) for placebo control (p = 0.648). The thrombolytic efficacy was 33% of the 250 mg plasmin group. There was no difference (p > 0.999) in thrombolytic efficacy with BOC (59%, 58/99) or without BOC (59%, 17/29). Plasmin-treated groups experienced treatment-emergent adverse events (TEAEs) at 71% (76/107) without BOC and 63% (24/38) with BOC; 78% (7/9) of the rtPA-treated group and 89% (8/9) of the placebo group had TEAEs. Serious AEs (SAEs) occurred in 29% (31/107) of the 150 mg plasmin group without BOC and 24% (9/38) with BOC. No SAEs occurred in the 250 mg plasmin group. Conclusions: Plasmin demonstrated less bleeding during catheter-directed administration at 150 mg and 250 mg doses compared to rtPA. BOC utilization did not improve efficacy. CDT with plasmin has a potential thrombolytic benefit in patients presenting with aPAO. ClinicalTrials.gov Identifier: NCT01222117.

Objective: The aim of this survey conducted by 20 leading Spanish oncologists was to analyze the concurrence between Spanish clinical practice and the recently published definition of the optimal sequence for the systemic treatment of metastatic breast cancer (MBC) according to patient profiles. Methods: A self-administered questionnaire was developed, divided into five sections comprising 34 specific questions related to sequential treatments, plus three additional general questions. Respondents were asked to justify negative answers. Participants were recruited randomly by invitation out of a total of 619 oncologists. The questionnaire was sent and collected via e-mail between October 2015 and May 2016. A total of 191 completed questionnaires were received. Results: Overall, 70% of oncologists would keep the three patient profiles exactly as proposed (hormone receptor-positive and HER2-negative, HER2-positive, and triple negative breast cancer). Affirmative answers to questions regarding treatment sequences for these patient profiles (1-34) ranged from 77.8-99.5%, with an average of 90.9% of oncologists being in agreement with the recommended sequential treatments. The lowest degree of consensus was observed for endocrine treatments in pre-menopausal women and for chemotherapy options in hormone-resistant patients, whilst the highest degree of consensus was reached for targeted therapies in HER2-positive patients and for endocrine therapy in post-menopausal women. In their comments, participants revealed a number of economic constraints that prevented them from implementing some of the best treatment options. Conclusions: In conclusion, despite the complexity of MBC treatment, there is general agreement on the optimal treatment sequences.