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- Eriksson, Carl, 1981-, et al.
(författare)
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Clinical effectiveness of golimumab in ulcerative colitis : a prospective multicentre study based on the Swedish IBD Quality Register, SWIBREG
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:11, s. 1304-1311
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Clinical trials demonstrated that golimumab is effective in anti-TNF naïve patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. Materials and methods: This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore ≥2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by ≥3 points or 30% from baseline) and remission (defined as a Mayo score of ≤2 with no individual subscores >1). Results: Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6–9) at baseline to 1 (0–5) at 52 weeks (p <.01) and the faecal calprotectin decreased from 862 (335–1759) µg/g to 90 (34–169) µg/g (p <.01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5‒1188.9). Conclusions: The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis.
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- Eriksson, Johanna, 1991-
(författare)
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Drug absorption in the lungs : studies in the isolated perfused rat lung model combined with physiologically based biopharmaceutics modelling
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pulmonary delivery of drugs is the preferred route of administration for treatment of local lung diseases like asthma and chronic obstructive pulmonary disease. Recently, there has also been increased interest in systemic delivery of drugs via the lungs to avoid problems with low and/or variable gastrointestinal absorption, and as a needle-free alternative for drugs that cannot be ingested. Both the pharmacological and the potentially adverse effects of inhaled drugs depend on the drug’s local and systemic concentrations, which in turn depend on the pulmonary absorption of the drug. Pulmonary drug absorption is governed by the dissolution, permeability, tissue retention, and non-absorptive clearance of the drug in the lungs. Predicting systemic and local exposure is necessary for developing an inhaled drug product, and these predictions can be based on data obtained from both in vitro and ex vivo methods, such as cell lines, solubility measurements, and the isolated perfused lung (IPL) model. Data obtained by these methods can then be used to inform physiologically based biopharmaceutics (PBB) models about drug-specific absorption parameters.The overall aim of this thesis was to increase the mechanistic understanding of pulmonary drug absorption, with a special focus on obtaining and analyzing ex vivo absorption parameters for different inhalation drugs and formulations, and evaluating the predictive power of these parameters in simulations of pulmonary drug absorption. In the first two papers of the thesis, drugs were formulated as solutions, suspensions, and dry powders, and pulmonary absorption of these were measured using the IPL model. The data from these experiments were then analyzed to obtain absorption parameters for each drug using a PBB model. Tissue retention was shown to be an important parameter for describing drug absorption in IPL, and particle wetting was shown to greatly affect the absorption of dry powders. Permeability in IPL correlated well with intrinsic permeability measured in cell monolayers, suggesting that passive transcellular transport is the main transport mechanism in the lungs. In the second two papers, the absorption parameters obtained from IPL data were used to simulate rat and human pulmonary drug absorption. The simulations predicted systemic exposure after inhalation well for both rat and human, suggesting that ex vivo parameters can be used to predict rat in vivo and human plasma concentrations. This thesis deepens our understanding of absorption parameters involved in pulmonary drug absorption, and suggests applications for these parameters in predictions of local and systemic exposure after inhalation.
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- Eriksson, Johanna, et al.
(författare)
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Drug Absorption Parameters Obtained Using the Isolated Perfused Rat Lung Model Are Predictive of Rat In Vivo Lung Absorption
- 2020
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Ingår i: AAPS Journal. - : SPRINGER. - 1550-7416. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- The ex vivo isolated perfused rat lung (IPL) model has been demonstrated to be a useful tool during drug development for studying pulmonary drug absorption. This study aims to investigate the potential use of IPL data to predict rat in vivo lung absorption. Absorption parameters determined from IPL data (ex vivo input parameters) in combination with intravenously determined pharmacokinetic data were used in a biopharmaceutics model to predict experimental rat in vivo plasma concentration-time profiles and lung amount after inhalation of five different inhalation compounds. The performance of simulations using ex vivo input parameters was compared with simulations using in vitro input parameters, to determine whether and to what extent predictability could be improved by using input parameters determined from the more complex ex vivo model. Simulations using ex vivo input parameters were within twofold average difference (AAFE < 2) from experimental in vivo data for all compounds except one. Furthermore, simulations using ex vivo input parameters performed significantly better than simulations using in vitro input parameters in predicting in vivo lung absorption. It could therefore be advantageous to base predictions of drug performance on IPL data rather than on in vitro data during drug development to increase mechanistic understanding of pulmonary drug absorption and to better understand how different substance properties and formulations might affect in vivo behavior of inhalation compounds.
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- Thörn, Jonathan, et al.
(författare)
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Quality assuring the quality assurance tool : Applying safety-critical concepts to test framework development
- 2022
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Ingår i: PeerJ Computer Science. - : PeerJ. - 2376-5992. ; 8, s. e1131-e1131
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Tidskriftsartikel (refereegranskat)abstract
- The quality of embedded systems is demonstrated by the performed tests. The quality of such tests is often dependent on the quality of one or more testing tools, especially in automated testing. Test automation is also central to the success of agile development. It is thus critical to ensure the quality of testing tools. This work explores how industries with agile processes can learn from safety-critical system development with regards to the quality assurance of the test framework development. Safety-critical systems typically need adherence to safety standards that often suggests substantial upfront documentation, plans and a long-term perspective on several development aspects. In contrast, agile approaches focus on quick adaptation, evolving software and incremental deliveries. This article identifies several approaches of quality assurance of software development tools in functional safety development and agile development. The extracted approaches are further analyzed and processed into candidate solutions, i.e., principles and practices for the test framework quality assurance applicable in an industrial context. An industrial focus group with experienced practitioners further validated the candidate solutions through moderated group discussions. The two main contributions from this study are: (i) 48 approaches and 25 derived candidate solutions for test framework quality assurance in four categories (development, analysis, run-time measures, and validation and verification) with related insights, e.g., a test framework should be perceived as a tool-chain and not a single tool, (ii) the perceived value of the candidate solutions in industry as collected from the focus group.
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