Personalising biologic therapy in psoriasis: Development, validation and user-testing of a precision dosing dashboard
Charlotte M. ThomasDavid BaudryZehra ArkirBola CokerTejus DasandiKingsley PowellMonica Arenas-HernandezJoanne LeungKrystal RawstronChioma NwaoguSarah ChapmanRichard WoolfAndrew PinkJuliet N. BarkerJoseph F. StandingCatherine SmithSatveer K. Mahil
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Abstract:
Rising numbers of individuals receiving psoriasis biologics achieve clear/nearly clear skin (disease control). Trial data indicate some maintain control with lower doses, especially those with higher serum drug concentrations. This indicates potential for Model-Informed Precision Dosing (MIPD), an advanced therapeutic drug monitoring technique, in guiding dose minimisation. We developed, validated, and user-tested a precision dosing dashboard. We applied a MIPD approach leveraging Bayesian estimation to predict individual pharmacokinetic (PK) parameters for personalised dosing recommendations. A PK model of the exemplar biologic risankizumab, derived from phase I-III psoriasis trial data (13123 observations/1899 patients), was externally validated using real-world UK psoriasis data. The Bayesian model (posterior prediction: mean absolute error 0.89 mg/L; mean percentage error 19.55%; root mean square error 1.24 mg/L; R2 0.86) had superior predictive power to the basic PK model (prior prediction). The model was incorporated into an interactive dashboard, enabling input of individual patient data (serum drug concentrations, model covariates). UK healthcare professionals rated the dashboard user-friendly and acceptable. Mean time to generate a dosing interval was 2 minutes. Our dashboard has potential to incorporate other biologics and extend across disease contexts (non-response, other inflammatory diseases) for optimal real-world impact of precision dosing on health and cost outcomes.Keywords:
Dashboard
Long term daily dosing for patients and families may be challenging due to food aversions, dosing protocols, and age of the patient. The few long term studies suggest that low quantity daily dosing is associated with passing higher dose challenges over the long term, whereas high dose maintenance may protect for longer avoidance intervals. We review the data for peanut and suggest several strategies for your patients.
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Drug ingestion may play an important role in the induction and exacerbation of psoriasis. Drugs may directly induce the occurrence of psoriasis in susceptible individuals, or cause the recurrence or exacerbation of preexisting psoriasis. In view of their relationship with psoriasis, drugs can be classified as follows: drugs that are definitely able to induce or exacerbate psoriasis (e.g., lithium), and drugs that are possible to induce or exacerbate psoriasis (e.g., interferon). Clinical and histological studies on drug-induced or-exacerbated psoriasis are helpful to investigate into the pathogenesis of psoriasis. Further studies are still needed for drugs that are possible to induce or exacerbate psoriasis, which may be of great importance for the prevention of psoriasis in susceptible individuals.
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Psoriasis; Pharmaceutical preparations; Lithium compounds; Antimalarials; Biological agents; Provoke; Exacerbate
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Objective To Investigate whether the PDEs activities is abnormal or not in psoriasis patients by detecting the PDEs activities of both psoriasis patients and healthy controls, and explore the potential role of PDEs activities changes in the pathogenesis of psoriasis. Methods PDEs activities were detected by using high performance liquid chromatography(HPLC) in 50 patients with psoriasis and 60 healthy controls. Results The PDEs activities is 10.40%±3.54% in psoriasis patients,and 8.60%±2.25% in the healthy controls. The PDEs activities in patients with psoriasis is significant higher than that in the controls (P0.05). Conclusions The PDEs activities may be a risk factor for psoriasis.
Pathogenesis
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Sun Exposure
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Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients
To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital.A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared.There were 47,181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error.Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors.The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors.
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【Objectives】 To test the expression levels of soluble CD147(sCD147) in plasma of psoriasis vulgaris(PV) patients and normal controls. Describe disease severity of PV with psoriasis lesion degree score(PASI) and analyze the correlation between the expression levels of sCD147 in psoriasis patients and disease severity. To test the expression levels of sCD147 in plasma of different subtypes of psoriasis patients, and study the roles of sCD147 play in the psoriasis classification. 【Methods】 Detect the expression levels of sCD147 in 74 PV patients and 41 normal controls by enzyme-linked immunosorbent assay(ELISA). Analyze the correlation between sCD147 expression levels and PASI score. Detect the expression levels of sCD147 of plasma in 10 patients with psoriasis pustulose(PP), 12 patients with arthritis psoriasis(PsA) and 7 patients with psoriasis erythrodermic(PE). Statistical analyze the difference of sCD147 expression levels in patients with different subtypes of psoriasis. 【Results】 The sCD147 expression levels in plasma of PV patients were significantly higher than those in normal controls(Ctrl)(P 0.01). Statistical analysis showed that there was no correlation between sCD147 expression level and PASI score(r =0.123, P =0.298). There was significant difference of sCD147 expression levels in different subtypes of psoriasis patients(PV PP PsA PE)(P 0.001). 【Conclusion】The expression levels of sCD147 is significantly increased in psoriasis patients. There is statistical significance of sCD147 expression levels in four subtypes of psoriasis. Thus, sCD147 may become a new target for psoriasis drug treatment.
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Studies have reported high prevalence of inappropriate dosing in patients with renal impairment, which was significantly reduced with pharmacists' interventions. The objective of this study was to assess the proportions of renal drug dosing errors following the implementation of pharmacists-led renal drug dosing adjustment program. This was a quasi-experimental study conducted at the King Abdul Aziz Medical City, a tertiary teaching hospital, Jeddah, Saudi Arabia. The study comprised of 3 phases. The pre-phase and post-phase evaluated drug orders for dosing appropriateness. During the intervention phase, a renal drug dosing adjustment program was implemented, which included educational sessions on dosing in renal insufficiency and a renal drug dosing guidance. The primary outcome was to assess the change in the proportions of dosing errors following the intervention. In the pre-phase, inappropriate dosing was noted in 20.1% (70/348) of orders that required dosing adjustment. Among the total dosing errors, 44.2% (31/70) were further corrected, and pharmacists have documented intervention in 48.3% (15/31) of the corrected orders. In the post-phase, inappropriate dosing was noted in 21.9% (76/346) of orders that required dosing adjustment. Among the total dosing errors, 39.4% (30/76) were further corrected, and pharmacists have documented intervention in 66.6% (20/30) of the corrected orders. There was no statistically significant difference in inappropriate drug dosing between pre-phase and post-phase with a P = 0.56. The intervention was not associated with significant reduction in renal dosing errors, although pharmacist involvement in the corrected orders orders increased after the implementation of the intervention. This may indicate the need to integrate renal dosing guidance into the hospital prescribing system to optimize drug dosing in renal patients.
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This chapter contains sections titled: Introduction History of psoriasis Who gets psoriasis? Biology of psoriasis Comorbidities associated with psoriasis Clinical variants of psoriasis Physical symptoms that accompany psoriasis Trigger factors in psoriasis Treatments for psoriasis Measuring quality of life Conclusion References
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Psoriasis treatment using psorinum autonosode is discussed. 50 years old male has been suffering from psoriasis for over three years with multiple psoriasis patches on his hands and feet. Psorinum autonosode was prepared from psoriasis scales using Korsakov’s method and taken twice a day. In about a month of taking the autonosode, the psoriasis patches disappeared completely and have not come back for over two years.
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Nivolumab has received regulatory approval to be given by weight-based or flat dosing every two weeks or by flat dosing every four weeks. However, flat dosing would lead to unnecessarily high doses for patients with lower body weight, increasing the drug usage and probability of toxicity. We review the rationale of using a four-weekly hybrid dosing strategy using weight-based and flat-dosing regimens adopted by some jurisdictions.
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