Abstract
Guidelines for the treatment of rheumatoid arthritis (RA) recommend the use of conventional synthetic disease modifying anti-rheumatic drugs (cs-DMARDs) at the onset of the disease and only ...in the case of therapeutic failure, the addition of a biological drug (b-DMARD) is suggested.
The study aimed to evaluate determinants for first-line biological treatment in patients with RA in clinical practice.
A cohort of patients with RA, resident in Lazio, a central Italian Region, where Rome is located, and with at least one disease modifying anti-rheumatic drugs (DMARD) prescription between 2010 and 2016 was selected using health information systems linkable with each other by an individual unique anonymous identifier. In particular RA cohort was defined retrieving all patients with at least a RA disease code in regional data claims (hospital discharge, exemption code, emergency department access, or therapeutic plan). Only new users were included and the first-line treatment was identified: cs-DMARD or b-DMARD.
Descriptive analysis according to type of DMARD treatment was performed. Through multivariate logistic regression models (odds ratio OR; confidence interval CI95%) determinants of therapy such as age, comorbidity, and comedication were investigated.
Finally, switching during the first year of treatment from cs-DAMARDs to b-DMARDs was analyzed.
DMARD-new users with RA were 5641; 7.1% of them with b-DMARD as first-line treatment. Considering the year of dispensing, this percentage ranged from 4.9% (2011) to 8.2% (2015). Among cs-DMARD the most prescribed active agent was methotrexate (59.3%), while among b-DMARD it was etarnecept (37.0%), followed by adalimumab (21.2%). The average age of the cohort was 54 years with 77% of women. Determinants of first-line b-DMARD use were: age (OR
65
= 3.7; 2.6–5.2, OR
30–45)vs>65
= 1.7; 1.2–2.4, OR
45–55)vs>65
= 1.6; 1.1–2.4, OR
55–65)vs>65
= 1.2; 0.8–1.7), cancers (OR = 2.3; 1.3–4.2), cardio-cerebrovascular disease (OR = 1.4; 1.0–1.9), use of non-steroidal anti-inflammatory drugs (NSAIDs) (OR = 0.6; 0.4–0.7) and corticosteroids (OR = 0.6; 0.5–0.7) in the 6 months preceding diagnosis.
In the first year of treatment, we observed a percentage of switch from cs-DMARDs to b-DMARDs of 7.9%.
In clinical practice, about 7% of patients with RA are prescribed with a b-DMARD as first-line treatment. This therapeutic option, even if not supported by guide lines, is mostly link to younger age and clinical profile of the patients.
Purpose
Infertility is a topic of growing interest, and female infertility is often treated with gonadotropins. Evidence regarding comparative safety and efficacy of different gonadotropin ...formulations is available from clinical studies, while real-world data are missing. The present study aims to investigate effectiveness and safety of treatment with different gonadotropin formulations in women undergoing medically assisted procreation treatments in Latium, a region in central Italy, through a real-world data approach.
Methods
A retrospective population-based cohort study in women between the ages of 18 and 45 years who were prescribed with at least one gonadotropin between 2007 and 2019 was conducted. Women were enrolled from the regional drug dispense registry, and data on their clinical history, exposure to therapeutic cycles (based on recombinant “REC” or extractives “EXT” gonadotropin, or combined protocol “CMD” (REC + EXT)), and maternal/infantile outcomes were linked from the regional healthcare administrative databases. Multivariate logistic regression models were applied to estimate the association between exposure and outcomes.
Results
Overall, 90,292 therapeutic cycles prescribed to 35,899 women were linked to pregnancies. Overall, 15.8% of cycles successfully led to pregnancy. Compared to extractives, recombinant and combined treatments showed a stronger association with conception rate (RR
REC
adj = 1.06, 95% CI: 1.01–1.12; RR
CBD
adj = 1.17, 95% CI: 1.11–1.24). Maternal outcomes occurred in less than 5% of deliveries, and no significant differences between treatments were observed (REC vs EXT, pre-eclampsia: RR adj = 1.24, 95% CI: 0.86–1.79, ovarian hyperstimulation syndrome: RR adj = 1.25, 95% CI: 0.59–2.65, gestational diabetes: RR adj = 1.06, 95% CI: 0.84–1.35). Regarding infantile outcomes, similar results were obtained for different gonadotropin formulations (REC vs EXT: low birth weight: RR adj = 0.98, 95% CI: 0.83–1.26, multiple births: RR adj = 1.06, 95% CI: 0.92–1.23, preterm birth: RR adj = 1.03, 95% CI: 0.92–1.26).
Conclusions
Efficacy and safety profiles of REC proved to be similar to those of EXT. Regarding the efficacy in terms of conception rate and birth rate, protocols using the combined approach performed slightly better. Outcomes related to maternal and infantile safety were generally very rare, and safety features were overlapping between gonadotropin formulations.
In an effort to ensure that physicians have access to reliable evidence on drug effectiveness and safety, the Italian Drug Agency launched a program to disseminate independent information.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Current guidelines recommend prophylaxis with granulocyte colony-stimulating factors (G-CSFs) for patients with cancer who are at greater risk of febrile neutropenia (FN) while receiving ...chemotherapy. G-CSF biosimilars are available and represent a savings opportunity; however, their uptake has thus far been low.
Objective
Our objective was to evaluate prescribing patterns for G-CSFs in the prevention of chemotherapy-related FN and to evaluate the impact of regional guidance on G-CSF prescription.
Methods
We conducted an observational drug-utilization study in the Lazio region of Italy using the Electronic Therapeutic Plan Registry, which collects information on G-CSF prescriptions reimbursed by the regional health service. This registry includes information on demographics, tumour, indication for G-CSF use and previous G-CSF exposure. All therapeutic plans (TPs) registered from 1 July 2015 to 30 June 2016 were selected. A pharmaceutical policy intervention was implemented in November 2015. We evaluated temporal trends regarding G-CSF substances and compared the frequency of TPs for each G-CSF substance during the pre- and post-intervention periods.
Results
A total of 7082 TPs were eligible for the analysis, corresponding to 6592 patients. The frequency of TPs prescribed after the intervention indicated a significant increase in the use of a filgrastim biosimilar (% difference: 14.4;
p
< 0.001) and significant decreases in the use of lenograstim (% difference: –6.0;
p
< 0.001) and pegfilgrastim (% difference: –7.8;
p
< 0.001). The temporal trends analysis showed an increase in TPs using a filgrastim biosimilar (from 34.4% in July 2015 to 49.8% in June 2016;
p
< 0.0001) and a decrease in TPs using lenograstim and pegfilgrastim.
Conclusions
This study shows it is possible to change attitudes towards the prescription of less expensive G-CSFs in the FN setting when the prescriber’s decision-making processes are supported by evidence that includes both regulatory and clinical information and the analysis of clinical practice data.
Introduction
The new call on independent research on drugs issued in October 2016 by the Italian Medicines Agency (AIFA) explicitly reported that proposals based on systematic reviews were not ...admissible, and no justification or explanation for this choice was given. Prompted by this policy decision, here, we briefly discuss the potential usefulness of systematic reviews in responding to regulatory needs. First, systematic reviews, by collecting, analysing and critically appraising all relevant studies on a specific topic, may be used by different stakeholders as a basis for making clinical and policy recommendations, including regulatory recommendations. Second, systematic reviews may advance knowledge as primary clinical research does. Third, systematic reviews may be particularly useful to detect signals of unknown adverse effects. Fourth, systematic reviews may be used to identify knowledge gaps.
Proposal
Systematic reviews may simultaneously produce new findings and summarize existing knowledge, with the potential of informing regulatory decisions more pragmatically and more rapidly than other research designs. We suggest that national and international calls on independent research on drugs should not put primary clinical research against systematic reviews, as it implies a focus on the methods instead of on the questions being asked. As most calls only broadly define the research areas and the topics to be covered, we argue that it should be up to the applicant to make a proposal on which design provides the most valid and useful answer, and up to the assessors to carefully check the validity, feasibility and relevance of such a proposal.
Ethics in health communication. Addis, Antonio; De Fiore, Luca
Recenti progressi in medicina,
2019 Jul-Aug, Letnik:
110, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Health communication must be based on open and multi-dimensional dialogue involving all stakeholders: public and private institutions, health professionals, industries, associations and, above all, ...citizens. Currently, communication suffers many problems related to bad research (unethical research, falsification of data, conflict of interest, incomplete reporting, spin and plagiarism) and to the limits of an academic system that does rewards quantity more than quality. A turnaround is needed, based on five major changes: establishing rules that can actually be followed; improve the quality of scientific information; accept and encourage open confrontation; allow citizens to be able to express and assert their needs; transform uncertainty from limit to value. The "Liberati's principles" must be reaffirmed: an honest communication must make the results of the research accessible to those who have to make decisions that affect their health; researchers must engage in studies that promise benefits to citizens and are not just useful to one's career or industry; before opening up new research fronts it is necessary to exhaust the potential of research already started; the definition of research priorities must be a transparent and shared process; the best evidence is the most relevant for citizens and patients. These principles and all ethical issues related should be part of educational programs for all health operators and researchers.
Place in therapy of olmesartan Addis, Antonio; Trotta, Francesco
Global & regional health technology assessment (Online),
06/2017, Letnik:
4, Številka:
1
Journal Article
In the context of the Gamma-Flash program, whose objective is to investigate the emission of high-energy gamma rays and neutrons during thunderstorms, a neutron detection system, based on ...scintillators coupled to photomultiplier tubes, has been developed. The neutrons emitted are generated by photoproduction reactions in the atmosphere, and they have a wide range of energies, from MeV down to meV. In this work, the effects of neutron irradiation on photomultiplier tubes and their power supply are investigated to assess and quantify the effects of irradiation on dark count rate and during data acquisition. The detection system was irradiated at the ChipIr beamline at ISIS Neutron and Muon Source (UK). During the irradiation of power supplies, an increase in dark-count rate has been observed, whose magnitude depends on the output voltages and the experimental parameters. In the specific case of our experiment, the dark-count rate went from an average value of zero to 40 and 120 counts per second at the operating voltage of 1800 V and at 1900V, respectively. Even more evident are the effects during the irradiation of the photomultiplier tubes, in this case, the dark-count rate reach about 4,000 counts per second, high enough to hamper the measurements. These effects, despite their relevance to data acquisition and detector performance, do not produce long-term consequences on the electronic components. Beyond the Gamma-Flash program, this research is relevant because the use of photomultiplier tubes is common in many areas of scientific research and radiation detection applications. Our results highlight the need for great care in the interpretation of results in applications where photomultiplier tubes and their power supplies may be exposed to high radiation fluxes. A proper design of the experiment or shielding strategies could prevent such unwanted behavior in data acquisition.
Several drugs share the same therapeutic indication, including those undergoing patent expiration. Concerns on the interchangeability are frequent in clinical practice, challenging the evaluation of ...switchability through observational research. The objective of this study was to conduct a scoping review of observational studies on drug switchability to identify methodological strategies adopted to deal with bias and confounding.
We searched PubMed, EMBASE, and Web of Science (updated January 31, 2017) to identify studies evaluating switchability in terms of effectiveness/safety outcomes or compliance. Three reviewers independently screened studies extracting all characteristics. Strategies to address confounding, particularly previous drug use and switching reasons, were considered. All findings were summarized in descriptive analyses.
Thirty-two studies, published in the last 10 years, met the inclusion criteria. Epilepsy, cardiovascular, and rheumatology were the most frequently represented clinical areas. Seventy-five percent of the studies reported data on effectiveness/safety outcomes. The most frequent study design was cohort (65.6%) followed by case–control (21.9%) and self-controlled (12.5%). Case–control and case–crossover studies showed homogeneous methodological strategies to deal with bias and confounding. Among cohort studies, the confounding associated with previous drug use was addressed introducing variables in multivariate model (47.3%) or selecting only adherent patients (14.3%). Around 30% of cohort studies did not report reasons for switching. In the remaining 70%, clinical parameters or previous occurrence of outcomes was measured to identify switching connected with lack of effectiveness or adverse events.
This study represents a starting point for researchers and administrators who are approaching the investigation and assessment of issues related to interchangeability of drugs.
PDF
