Guselkumab is an IL-23 inhibitor approved for moderate-to-severe plaque psoriasis that has demonstrated safety and efficacy in phase III clinical trials
. However, there is scarce data regarding its ...drug survival in clinical practice.
Summary
Background
Patients with moderate‐to‐severe psoriasis treated with adalimumab in daily clinical practice are different from those in clinical trials, and outcomes may differ in different ...geographical settings.
Objectives
To analyse the efficacy, retention of treatment and adverse events in a cohort of such patients at a referral centre in Barcelona, Spain.
Methods
Data from a cohort of 119 consecutive patients treated between January 2008 and March 2013 were retrospectively collected. Drug survival was analysed by the Kaplan–Meier method with log‐rank test and Cox regression.
Results
The mean duration of treatment was 25 months (median 22, range 2–60). The 75% improvement in Psoriasis Area and Severity Index (PASI 75) response rates at 16 weeks, 6 months and 1 year of treatment were 64%, 58% and 53%, respectively (intention‐to‐treat analysis). The corresponding PASI 90 values were 49%, 52% and 50%. Biologic‐naive patients (41%) had significantly higher PASI 75 and PASI 90 response rates at 6 months and 1 year. On multivariate analysis, only PASI 90 response at 6 months was significantly associated with treatment retention (P = 0·0009), with a hazard ratio of 7·3 (95% confidence interval 2·3–23·6). Forty‐eight adverse events (AEs) occurred in 29 patients, and were serious in eight (0·032 events per patient‐year). Paradoxical flares of psoriasis or arthritis were seen in five patients. Infections accounted for seven serious AEs, and were the reason for discontinuation in two patients.
Conclusions
PASI 90 response at 6 months was the only independent variable predicting drug survival on multivariate analysis. Infections, including de novo infection by Mycobacterium tuberculosis, accounted for seven serious AEs.
What's already known about this topic?
There are few reports on the use of adalimumab for the treatment of moderate‐to‐severe psoriasis in clinical practice according to the European Medicines Agency.
Psoriasis Area and Severity Index (PASI) 75% response rates at 16 weeks and 6 months were approximately 60% in a previously published U.K. series.
Male sex and the presence of arthritis have been associated with decreased drug survival in one study.
What does this study add?
Biologic‐naive status and efficacy parameters denoting a good or excellent response appear to be associated with a higher probability of drug survival.
Combination treatment increased PASI response rates at 6 months and might provide an explanation for the relatively high rate of PASI 90 responders in our cohort.
Infections, including de novo infection by Mycobacterium tuberculosis, accounted for most serious adverse events, and paradoxical flares of psoriasis and psoriatic arthritis were relatively frequent.
Weed mapping at very early phenological stages of crop and weed plants for site-specific weed management can be achieved by using ultra-high spatial and high spectral resolution imagery provided by ...multispectral sensors on-board an unmanned aerial vehicle (UAV). These UAV images cannot cover the whole field, resulting in the need to take a sequence of multiple overlapped images. Therefore, the overlapped images must be oriented and ortho-rectified to create an accurate ortho-mosaicked image of the entire field for further classification. Because the spatial quality of ortho-mosaicked images mainly depend on the flight altitude and percentage of overlap, this paper describes the effect of flight parameters using a multirotor UAV and a multispectral camera on the mosaicking workflow. The objective is to define the best configuration for the mission planning to generate accurate ortho-images. A set of flights with a range of altitudes (30, 40, 50, 60, 70, 80, and 90 m) above ground level (AGL) and two end-lap and side-lap settings (60-30% and 70-40%) were studied. The spatial accuracy of ortho-mosaics was evaluated taking into consideration the ASPRS test. The results showed that the best flight setting to keep the spatial accuracy in the bundle adjustment was 70-40% overlap and altitudes AGL ranging from 60 to 90 m. At these flight altitudes, the spatial resolution was quite similar, making it possible to optimize the mission planning, flying at a higher altitude and increasing the area overflow without decreasing the ortho-mosaic spatial quality. This study has relevant implications for further use in detecting weed seedlings in crops.
Definition of minimal disease activity in psoriasis Carretero, G.; Carrascosa, J.M.; Puig, L. ...
Journal of the European Academy of Dermatology and Venereology,
February 2021, 2021-Feb, 2021-02-00, 20210201, Letnik:
35, Številka:
2
Journal Article
Recenzirano
Objective
To generate an operational definition to adequately reflect the construct ‘Minimal Disease Activity (MDA)’ in psoriasis.
Methods
A systematic review of domains included in clinical trials ...of psoriasis was presented to a panel of dermatologists and patients. Further domains were elicited by panel discussions. Domains (and instruments measuring these) were items of two consecutive Delphi rounds targeting dermatologists from the Psoriasis Group of the Spanish Academy of Dermatology and Venereology and patients from the Acción Psoriasis association. The instruments selected were used to generate 388 patient vignettes. The expert group then classified these vignettes as ‘No MDA/MDA/Unclassifiable’. The items were further reduced by factorial analysis. Using the classification variable as gold standard, several operational constructions were tested in regression models and ROC curves and accuracy was evaluated with area under the curve (AUC).
Results
The following domains were included: itching, scaling, erythema and visibility by 0–10 scales, extension by BSA, impact on quality of life by DLQI, special location and presence of arthritis as yes/no. The definition with the highest AUC and best balance between sensitivity and specificity was the one including no presence of arthritis plus at least three others below the upper limit of the 95% confidence interval (AUC, 0.897; sensitivity, 95.2%, specificity, 84.1%).
Conclusion
This study provides, for the very first time, the construct of ‘Minimal Disease Activity’ in psoriasis as agreed by dermatologists and patients. MDA is defined as absence of active arthritis plus 3 out of 6: itching ≤ 1/10; scaling ≤ 2/10; redness ≤ 2/10; visibility ≤ 2/10; BSA ≤ 2; DLQI ≤ 2; and no lesions in special locations. By design, domains are representative of disease impact. This MDA definition may be used as a measure of adequate management and replace other subjective or restrictive tools.
In this study, low-intensity microwave irradiation (frequency of 2.45 GHz; 26.3 kW m–3 power density) for 0, 5, and 30 s was tested for the first time on Drosera rotundifolia in vitro plantlets to ...explore its effect on the production of highly valued phenolic compounds. Analysis of the extracts obtained from irradiated plantlets revealed time-dependent increases in the levels of photosynthetic pigments, particularly the carotenoids, whereas symptoms of growth decline were not observed. Similarly, the highest total antioxidant capacity and total phenolic and flavonoid contents were detected in 30-s-irradiated plantlets. High-performance liquid chromatography analysis revealed that the content of the bioactive phenolics 5-hydroxy-7-methylnaphthalene-1,4-dione (1), 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (2), and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yloxychromen-4-one (3), which are considered to be responsible for the pharmacological properties of this species, was around twofold higher in 30-s-irradiated plantlets than in controls. Nevertheless, the accumulation of 5-hydroxy-2-methylnaphthalene-1,4-dione (4), which was present only in trace amounts in the plant roots, decreased by 30% upon microwave irradiation. The results indicate that microwave treatment acts as an effective inducer of the production of phenylpropanoid compounds, which opens up new opportunities for its use in biotechnological applications.
Background
Infiximab has been shown to be highly effective in phase III clinical trials, but limited information is available regarding drug survival and maintenance of efficacy beyond 1 year in ...real‐life clinical setting.
Objectives
To analyse the efficacy and safety of infliximab in a large number of patients with a long follow‐up and to identify clinical factors associated with long‐term drug survival.
Methods
A retrospective review of patients with moderate‐to‐severe psoriasis treated with infliximab from March 2004 to August 2012 at a tertiary dermatology centre was carried out.
Results
In total, 63 treatment courses with infliximab were administered to 56 patients. The mean duration of treatment was 31.6 months. The only significant positive predictor of drug survival was combination treatment hazard ratio (HR) vs. monotherapy 2.90, 95% confidence interval (CI) 1.42–5.92. Significant negative predictors of drug survival were obesity (HR 0.40, 95% CI 0.19–0.87) and infusion reactions (HR 0.40, 95% CI 0.19–0.87). Infusion reactions occurred in 13 (23%) of our patients and were a reason for discontinuation of treatment in 5.
Conclusions
This retrospective review of a cohort of patients with moderate‐to‐severe psoriasis treated with infliximab in daily practice shows that the PASI75 response rates at 24 and 52 weeks of treatment are similar to those of the pivotal studies, but 37 courses of treatment (59%) had to be discontinued after a median of 12 months. The major cause for discontinuation was loss of response, in 18 cases. Combination treatment, obesity and infusion reactions were found to be predictors of drug survival.
Background
Nail psoriasis disease is associated with an increased probability of psoriatic arthritis, and its clinical signs may have different correlates with the pathogenesis of adjacent bone ...destruction and have different prognostic value. Recent publications about psoriasis and nail psoriatic disease describe different ultrasonographic findings but the relationship between these ungueal alterations measured by ultrasonography and the presence of enthesopathy of the extensor digitorum has yet to be discovered.
Objective
To describe which ultrasonographic characteristics of nail psoriasis are associated with the presence of subclinical enthesopathy in patients with PsO and asymptomatic PsA.
Methods
Patients with psoriasis and asymptomatic psoriatic arthritis were included in the prospective study. Demographic, clinical data and PASI and NAPSI indexes were recorded of all the patients in the assessment visit. The US assessment included Achilles tendon, extensor digitorum tendon and US scan of the nail plate, nail matrix, nail bed and adjacent skin over nail matrix of the five nails of each hand.
Results
Forty‐eight patients were included in the study; 33 of them presented ultrasound evidence of extensor digitorum tendon enthesopathy. Nails of the patients with subclinical enthesopathy had a higher NAPSI and skin thickness than the nails of the patients without subclinical enthesopathy (P = 0.047). Patients with asymptomatic enthesopathy had significantly thicker proximal nail folds (1.44 ± 0.312 vs. 1.23 ± 0.27, P = 0.023). Nail beds and matrices were also thicker but the differences were not statistically significant (1.77 ± 0.27 vs. 1.74 ± 0.21, P = 0.66, and 1.79 ± 0.28 vs. 1.67 ± 0.19, P = 0.10, respectively). No statistically significant differences in the trilaminar structure were found between both groups. Patients with and without asymptomatic enthesopathy of extensor digitorum tendons did not statistically differ as regards ultrasonographic alterations of the Achilles tendons (60.6% vs. 46.4%, P 0.368).
Conclusion
Enthesopathy abnormalities can be detected by US in patients with psoriasis without musculoskeletal complaints frequently. There is a close relationship between subclinical enthesopathy of the extensor digitorum tendon and the presence of nail alterations. Further studies are required to research what implications have the presence of these ungual alterations measured by US, and how it affects later development of a PsA.
Background
Little has been published on the real‐world effectiveness and safety of apremilast in psoriasis.
Objectives
To evaluate the effectiveness, safety and drug survival of apremilast at ...52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice.
Methods
Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018.
Results
We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI‐75 (≥75% reduction in PASI score) and 26.5% achieved PASI‐90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems.
Conclusions
Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.
Background
Ixekizumab (anti‐IL17A) is effective as treatment for moderate‐to‐severe plaque psoriasis, but real‐life data on effectiveness and safety are currently very limited.
Objective
To evaluate ...the efficacy and safety of ixekizumab in a cohort of real‐life plaque psoriasis patients.
Methods
Retrospective chart review of 100 patients with moderate‐to‐severe plaque psoriasis treated with ixekizumab at seven Spanish dermatological centres.
Results
According to the as observed analysis, the percentage of patients achieving a 75% and 90% of reduction from the baseline score of Psoriasis Area and Severity Index (PASI) was 87.5%–50.0% at week 12–16; 88.3%–58.4% at week 24 and 82.9%–58.5% at week 52, respectively. The mean ± standard deviation (SD) score of PASI at baseline was 12.9 ± 9.2, and it declined rapidly after ixekizumab administration to 1.9 ± 4.0 (P < 0.001) at week 12–16 and was maintained at 1.7 ± 4.1 and 1.8 ± 2.9 at week 24 and 52, respectively. Ixekizumab response was not affected by clinical variables like body mass index, disease duration or the presence of psoriatic arthritis. However, the bio‐naive group showed significantly higher PASI 75 response rate at week 12–16 compared to patients previously exposed to biologic agents (P = 0.037). Twenty‐six (26%) patients experienced adverse events (AEs) during the follow‐up period, being most of them of mild‐to‐moderate intensity. The most common AE was local reaction at the site of injection (14/26; 53.8%). At the end of the observational period, 15 (15%) patients discontinued ixekizumab treatment due to limited clinical improvement (n = 11), adverse events (n = 3) or lost to follow‐up (n = 1) within a mean ± SD time of 6.0 ± 3.9 months.
Conclusion
The present study illustrates the initial experience with ixekizumab in real‐world clinical practice confirming its usefulness and safety in the management of plaque psoriasis patients.
Background and Purpose
FM19G11 up‐regulates mammalian target of rapamycin (mTOR)/hypoxia inducible factor‐1α (HIF‐1α) and PI3K/Akt pathways, which are involved in endothelial function. We evaluated ...the effects of FM19G11 on defective endothelial vasodilatation in arteries from rats and humans and investigated the mechanisms involved.
Experimental Approach
Effects of chronic in vivo administration of FM19G11 on aortic endothelial vasodilatation were evaluated together with ex vivo treatment in aortic and mesenteric arteries from control and insulin‐resistant rats (IRR). Its effects on vasodilator responses of penile arteries (HPRAs) and corpus cavernosum (HCC) from men with vasculogenic erectile dysfunction (ED) (model of human endothelial dysfunction) were also evaluated. Vascular expression of phosphorylated‐endothelial NOS (p‐eNOS), phosphorylated‐Akt (p‐Akt) and HIF‐1α was determined by immunodetection and cGMP by elisa.
Key Results
Chronic administration of FM19G11 reversed the impaired endothelial vasodilatation in IRR. Ex vivo treatment with FM19G11 also significantly improved endothelium‐dependent vasodilatation in aorta and mesenteric arteries from IRR. These effects were accompanied by the restoration of p‐eNOS and cGMP levels in IRR aorta and were prevented by either NOS or PI3K inhibition. p‐Akt and p‐eNOS contents were increased by FM19G11 in aortic endothelium of IRR. FM19G11‐induced restoration of endothelial vasodilatation was unaffected by mTOR/HIF‐1α inhibitors. FM19G11 also restored endothelial vasodilatation in HPRA and HCC from ED patients.
Conclusions and Implications
Stimulation of the PI3K/Akt/eNOS pathway by FM19G11 alleviates impaired NO‐mediated endothelial vasodilatation in rat and human arteries independently of mTOR/HIF‐1α activation. This pharmacological strategy could be beneficial for managing pathological conditions associated with endothelial dysfunction, such as ED.
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