25 research outputs found
Quantifying the Effect of Methotrexate on Adalimumab Response in Psoriasis by PharmacokineticâPharmacodynamic Modeling
Previously, we showed that the combination of methotrexate and adalimumab treatment leads to less antidrug antibody development. In this study, we quantify the pharmacokinetics/pharmacodynamics (PK/PD) of adalimumab and evaluate the influence of methotrexate cotreatment. A population PKâPD model was developed using prospective data from 59 patients with psoriasis (baseline PASI = 12.6) receiving adalimumab over 49 weeks. Typical PK and PD parameters and their corresponding interpatient variability were estimated. We performed a covariate analysis to assess whether interpatient variability could be explained by addition of methotrexate and other covariates. In total, 330 PASIs, 252 adalimumab serum concentrations, and 247 antidrug antibody titers were available. Presence of antidrug antibodies (adalimumab group = 46.7%, adalimumab + methotrexate group = 38.7%; P = .031) was correlated with increased adalimumab apparent clearance (P < .001). In the PD model, the use of concomitant methotrexate was borderline to significantly correlated with a decreased half-maximal inhibitory concentration (adalimumab concentration for which clinical response score is reduced by half; P < .10). On the basis of our PKâPD model, concomitant use of methotrexate indirectly increases adalimumab concentration, partially through less antidrug antibodies formation, which may result in better efficacy.</p
Phototherapy for atopic eczema
BACKGROUND: Atopic eczema (AE), also known as atopic dermatitis, is a chronic inflammatory skin condition that causes significant burden. Phototherapy is sometimes used to treat AE when topical treatments, such as corticosteroids, are insufficient or poorly tolerated. OBJECTIVES: To assess the effects of phototherapy for treating AE. SEARCH METHODS: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and ClinicalTrials.gov to January 2021. SELECTION CRITERIA: We included randomised controlled trials in adults or children with any subtype or severity of clinically diagnosed AE. Eligible comparisons were any type of phototherapy versus other forms of phototherapy or any other treatment, including placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. For key findings, we used RoB 2.0 to assess bias, and GRADE to assess certainty of the evidence. Primary outcomes were physicianâassessed signs and patientâreported symptoms. Secondary outcomes were Investigator Global Assessment (IGA), healthârelated quality of life (HRQoL), safety (measured as withdrawals due to adverse events), and longâterm control. MAIN RESULTS: We included 32 trials with 1219 randomised participants, aged 5 to 83 years (mean: 28 years), with an equal number of males and females. Participants were recruited mainly from secondary care dermatology clinics, and study duration was, on average, 13 weeks (range: 10 days to one year). We assessed risk of bias for all key outcomes as having some concerns or high risk, due to missing data, inappropriate analysis, or insufficient information to assess selective reporting. Assessed interventions included: narrowband ultraviolet B (NBâUVB; 13 trials), ultraviolet A1 (UVA1; 6 trials), broadband ultraviolet B (BBâUVB; 5 trials), ultraviolet AB (UVAB; 2 trials), psoralen plus ultraviolet A (PUVA; 2 trials), ultraviolet A (UVA; 1 trial), unspecified ultraviolet B (UVB; 1 trial), full spectrum light (1 trial), Saalmann selective ultraviolet phototherapy (SUP) cabin (1 trial), saltwater bath plus UVB (balneophototherapy; 1 trial), and excimer laser (1 trial). Comparators included placebo, no treatment, another phototherapy, topical treatment, or alternative doses of the same treatment. Results for key comparisons are summarised (for scales, lower scores are better): NBâUVB versus placebo/no treatment There may be a larger reduction in physicianâassessed signs with NBâUVB compared to placebo after 12 weeks of treatment (mean difference (MD) â9.4, 95% confidence interval (CI) â3.62 to â15.18; 1 trial, 41 participants; scale: 0 to 90). Two trials reported little difference between NBâUVB and no treatment (37 participants, four to six weeks of treatment); another reported improved signs with NBâUVB versus no treatment (11 participants, nine weeks of treatment). NBâUVB may increase the number of people reporting reduced itch after 12 weeks of treatment compared to placebo (risk ratio (RR) 1.72, 95% CI 1.10 to 2.69; 1 trial, 40 participants). Another trial reported very little difference in itch severity with NBâUVB (25 participants, four weeks of treatment). The number of participants with moderate to greater global improvement may be higher with NBâUVB than placebo after 12 weeks of treatment (RR 2.81, 95% CI 1.10 to 7.17; 1 trial, 41 participants). NBâUVB may not affect rates of withdrawal due to adverse events. No withdrawals were reported in one trial of NBâUVB versus placebo (18 participants, nine weeks of treatment). In two trials of NBâUVB versus no treatment, each reported one withdrawal per group (71 participants, 8 to 12 weeks of treatment). We judged that all reported outcomes were supported with lowâcertainty evidence, due to risk of bias and imprecision. No trials reported HRQoL. NBâUVB versus UVA1 We judged the evidence for NBâUVB compared to UVA1 to be very low certainty for all outcomes, due to risk of bias and imprecision. There was no evidence of a difference in physicianâassessed signs after six weeks (MD â2.00, 95% CI â8.41 to 4.41; 1 trial, 46 participants; scale: 0 to 108), or patientâreported itch after six weeks (MD 0.3, 95% CI â1.07 to 1.67; 1 trial, 46 participants; scale: 0 to 10). Two splitâbody trials (20 participants, 40 sides) also measured these outcomes, using different scales at seven to eight weeks; they reported lower scores with NBâUVB. One trial reported HRQoL at six weeks (MD 2.9, 95% CI â9.57 to 15.37; 1 trial, 46 participants; scale: 30 to 150). One splitâbody trial reported no withdrawals due to adverse events over 12 weeks (13 participants). No trials reported IGA. NBâUVB versus PUVA We judged the evidence for NBâUVB compared to PUVA (8âmethoxypsoralen in bath plus UVA) to be very low certainty for all reported outcomes, due to risk of bias and imprecision. There was no evidence of a difference in physicianâassessed signs after six weeks (64.1% reduction with NBâUVB versus 65.7% reduction with PUVA; 1 trial, 10 participants, 20 sides). There was no evidence of a difference in marked improvement or complete remission after six weeks (odds ratio (OR) 1.00, 95% CI 0.13 to 7.89; 1 trial, 9/10 participants with both treatments). One splitâbody trial reported no withdrawals due to adverse events in 10 participants over six weeks. The trials did not report patientâreported symptoms or HRQoL. UVA1 versus PUVA There was very lowâcertainty evidence, due to serious risk of bias and imprecision, that PUVA (oral 5âmethoxypsoralen plus UVA) reduced physicianâassessed signs more than UVA1 after three weeks (MD 11.3, 95% CI â0.21 to 22.81; 1 trial, 40 participants; scale: 0 to 103). The trial did not report patientâreported symptoms, IGA, HRQoL, or withdrawals due to adverse events. There were no eligible trials for the key comparisons of UVA1 or PUVA compared with no treatment. Adverse events Reported adverse events included low rates of phototoxic reaction, severe irritation, UV burn, bacterial superinfection, disease exacerbation, and eczema herpeticum. AUTHORS' CONCLUSIONS: Compared to placebo or no treatment, NBâUVB may improve physicianârated signs, patientâreported symptoms, and IGA after 12 weeks, without a difference in withdrawal due to adverse events. Evidence for UVA1 compared to NBâUVB or PUVA, and NBâUVB compared to PUVA was very low certainty. More information is needed on the safety and effectiveness of all aspects of phototherapy for treating AE
The BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) Glossary: developing a lingua franca to facilitate data harmonisation and cross-cohort analyses
Dear Editor, BIOMAP (BIOMarkers in Atopic dermatitis and Psoriasis) is a large European consortium aiming to advance personalised medicine for atopic dermatitis and psoriasis by identifying biomarkers which predict therapeutic response and disease progression. BIOMAP brings together clinicians, researchers, patient organisations and pharmaceutical industry partners and encompasses data from over 60 individual studies, including randomised clinical trials, population-based cohorts and deeply-phenotyped disease registries. The curation and harmonisation of data and bio-samples from these established studies will facilitate cross-cohort clinical and molecular analyses, increasing the potential to identify small effect estimates and to better stratify disease subtypes. This letter serves to disseminate BIOMAP's pathway to data harmonisation and will inform future collaborative research endeavours
Adalimumab with Methotrexate vs. Adalimumab Monotherapy in Psoriasis: First-Year Results of a Single-Blind Randomized Controlled Trial
Introduction: Adalimumab is normally prescribed with methotrexate (MTX) in rheumatoid arthritis given the enhanced treatment effect and reduced antidrug antibody formation compared with adalimumab monotherapy (ADL). In psoriasis, the long-term treatment effects and pharmacokinetic profile have not been investigated extensively. Methods: We conducted a randomized controlled trial to assess the efficacy, safety, pharmacokinetics, and immunogenicity of adalimumab combined with MTX 10 mg per week (ADL-MTX group) compared with that of ADL (ADL group) in chronic plaque psoriasis. Results: A total of 31 patients in the ADL-MTX group and 30 in the ADL group were analyzed. After 1 year, a (nonsignificant) better drug survival was found in the ADL-MTX group (74.2 vs. 58.6%, P = 0.15). The PASI 75 response in week 49 was 58.1 versus 36.7% (P = 0.13), and the median (interquartile range) serum-trough concentrations were 6.8 (5.5â9.2) versus 5.9 (3.5â8.8) mg/l (P = 0.26) in the ADL-MTX group and ADL group, respectively. Fewer patients showed antidrug antibodies in the ADL-MTX group (22.6 vs. 60.0%, P < 0.01). No serious adverse events occurred. Conclusion: Combination therapy of adalimumab and MTX results in fewer patients showing antidrug antibodies, with a trend toward a better PASI 75 response, drug survival, and higher serum-trough concentrations than ADL. Patient-reported outcomes and adverse events were comparable between the groups
Mapping exercise and status update of eight established registries within the TREatment of ATopic eczema Registry Taskforce
Background: The TREatment of ATopic eczema (TREAT) Registry Taskforce is a collaborative international network of registries collecting data of atopic eczema (AE) patients receiving systemic and phototherapy with the common goal to provide long-term real-world data on the effectiveness, safety and cost-effectiveness of therapies. A core dataset, consisting of domains and domain items with corresponding measurement instruments, has been developed to harmonize data collection. Objectives: We aimed to give an overview of the status and characteristics of the eight established TREAT registries, and to perform a mapping exercise to examine the degree of overlap and pooling ability between the national registry datasets. This will allow us to determine which research questions can be answered in the future by pooling data. Methods: All eight registries were asked to share their dataset and information on the current status and characteristics. The overlap between the core dataset and each registry dataset was identified (according to the domains, domain items and measurement instruments of the TREAT core dataset). Results and conclusions: A total of 4702 participants have been recruited in the eight registries as of 1st of May 2022. Of the 69 core dataset domain items, data pooling was possible for 69 domain item outcomes in TREAT NL (the Netherlands), 61 items in A-STAR (UK and Ireland), 38 items in TREATgermany (Germany), 36 items in FIRST (France), 33 items in AtopyReg (Italy), 29 items in Biobadatop (Spain), 28 items in SCRATCH (Denmark) and 20 items in SwedAD (Sweden). Pooled analyses across all registries can be performed on multiple important domain items, covering the main aims of analysing data on the (cost-)effectiveness and safety of AE therapies. These results will facilitate future comparative or joint analyses
Mapping exercise and status update of eight established registries within the TREatment of ATopic eczema Registry Taskforce
Background: The TREatment of ATopic eczema (TREAT) Registry Taskforce is a collaborative international network of registries collecting data of atopic eczema (AE) patients receiving systemic and phototherapy with the common goal to provide long-term real-world data on the effectiveness, safety and cost-effectiveness of therapies. A core dataset, consisting of domains and domain items with corresponding measurement instruments, has been developed to harmonize data collection. Objectives: We aimed to give an overview of the status and characteristics of the eight established TREAT registries, and to perform a mapping exercise to examine the degree of overlap and pooling ability between the national registry datasets. This will allow us to determine which research questions can be answered in the future by pooling data. Methods: All eight registries were asked to share their dataset and information on the current status and characteristics. The overlap between the core dataset and each registry dataset was identified (according to the domains, domain items and measurement instruments of the TREAT core dataset). Results and conclusions: A total of 4702 participants have been recruited in the eight registries as of 1st of May 2022. Of the 69 core dataset domain items, data pooling was possible for 69 domain item outcomes in TREAT NL (the Netherlands), 61 items in A-STAR (UK and Ireland), 38 items in TREATgermany (Germany), 36 items in FIRST (France), 33 items in AtopyReg (Italy), 29 items in Biobadatop (Spain), 28 items in SCRATCH (Denmark) and 20 items in SwedAD (Sweden). Pooled analyses across all registries can be performed on multiple important domain items, covering the main aims of analysing data on the (cost-)effectiveness and safety of AE therapies. These results will facilitate future comparative or joint analyses
The effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis: Results from the global SECURE-AD registry
Background: Limited data are available on the effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis (AD). Objective: To investigate COVID-19 outcomes in patients with AD treated with or without systemic immunomodulatory treatments, using a global registry platform. Methods: Clinicians were encouraged to report cases of COVID-19 in their patients with AD in the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Atopic Dermatitis (SECURE-AD) registry. Data entered from 1 April 2020 to 31 October 2021 were analysed using multivariable logistic regression. The primary outcome was hospitalization from COVID-19, according to AD treatment groups. Results: 442 AD patients (mean age 35.9 years, 51.8% male) from 27 countries with strongly suspected or confirmed COVID-19 were included in analyses. 428 (96.8%) patients were treated with a single systemic therapy (n = 297 [67.2%]) or topical therapy only (n = 131 [29.6%]). Most patients treated with systemic therapies received dupilumab (n = 216). Fourteen patients (3.2%) received a combination of systemic therapies. Twenty-six patients (5.9%) were hospitalized. No deaths were reported. Patients treated with topical treatments had significantly higher odds of hospitalization, compared with those treated with dupilumab monotherapy (odds ratio (OR) 4.65 [95%CI 1.71â14.78]), including after adjustment for confounding variables (adjusted OR (aOR) 4.99 [95%CI 1.4â20.84]). Combination systemic therapy which did not include systemic corticosteroids was associated with increased odds of hospitalization, compared with single agent non-steroidal immunosuppressive systemic treatment (OR 8.09 [95%CI 0.4â59.96], aOR 37.57 [95%CI 1.05â871.11]). Hospitalization was most likely in patients treated with combination systemic therapy which included systemic corticosteroids (OR 40.43 [95%CI 8.16â207.49], aOR 45.75 [95%CI 4.54â616.22]). Conclusions: Overall, the risk of COVID-19 complications appears low in patients with AD, even when treated with systemic immunomodulatory agents. Dupilumab monotherapy was associated with lower hospitalization than other therapies. Combination systemic treatment, particularly combinations including systemic corticosteroids, was associated with the highest risk of severe COVID-19
The effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis: Results from the global SECURE-AD registry
Background: Limited data are available on the effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis (AD). Objective: To investigate COVID-19 outcomes in patients with AD treated with or without systemic immunomodulatory treatments, using a global registry platform. Methods: Clinicians were encouraged to report cases of COVID-19 in their patients with AD in the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Atopic Dermatitis (SECURE-AD) registry. Data entered from 1 April 2020 to 31 October 2021 were analysed using multivariable logistic regression. The primary outcome was hospitalization from COVID-19, according to AD treatment groups. Results: 442 AD patients (mean age 35.9 years, 51.8% male) from 27 countries with strongly suspected or confirmed COVID-19 were included in analyses. 428 (96.8%) patients were treated with a single systemic therapy (n = 297 [67.2%]) or topical therapy only (n = 131 [29.6%]). Most patients treated with systemic therapies received dupilumab (n = 216). Fourteen patients (3.2%) received a combination of systemic therapies. Twenty-six patients (5.9%) were hospitalized. No deaths were reported. Patients treated with topical treatments had significantly higher odds of hospitalization, compared with those treated with dupilumab monotherapy (odds ratio (OR) 4.65 [95%CI 1.71â14.78]), including after adjustment for confounding variables (adjusted OR (aOR) 4.99 [95%CI 1.4â20.84]). Combination systemic therapy which did not include systemic corticosteroids was associated with increased odds of hospitalization, compared with single agent non-steroidal immunosuppressive systemic treatment (OR 8.09 [95%CI 0.4â59.96], aOR 37.57 [95%CI 1.05â871.11]). Hospitalization was most likely in patients treated with combination systemic therapy which included systemic corticosteroids (OR 40.43 [95%CI 8.16â207.49], aOR 45.75 [95%CI 4.54â616.22]). Conclusions: Overall, the risk of COVID-19 complications appears low in patients with AD, even when treated with systemic immunomodulatory agents. Dupilumab monotherapy was associated with lower hospitalization than other therapies. Combination systemic treatment, particularly combinations including systemic corticosteroids, was associated with the highest risk of severe COVID-19
Learning from disease registries during a pandemic:Moving toward an international federation of patient registries
High-quality dermatology patient registries often require considerable time to develop and produce meaningful data. Development time is influenced by registry complexity and regulatory hurdles that vary significantly nationally and institutionally. The rapid emergence of the coronavirus disease 2019 (COVID-19) global pandemic has challenged health services in an unprecedented manner. Mobilization of the dermatology community in response has included rapid development and deployment of multiple, partially harmonized, international patient registries, reinventing established patient registry timelines. Partnership with patient organizations has demonstrated the critical nature of inclusive patient involvement. This global effort has demonstrated the value, capacity, and necessity for the dermatology community to adopt a more cohesive approach to patient registry development and data sharing that can lead to myriad benefits. These include improved utilization of limited resources, increased data interoperability, improved ability to rapidly collect meaningful data, and shortened response times to generate real-world evidence. We call on the global dermatology community to support the development of an international federation of patient registries to consolidate and operationalize the lessons learned during this pandemic. This will provide an enduring means of applying this knowledge to the maintenance and development of sustainable, coherent, and impactful patient registries of benefit now and in the future