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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.

Core outcome sets are critically important outcomes that should be measured in clinical trials. Their absence in atopic dermatitis is a form of research waste and impedes combining evidence to inform patient care. Here, we articulate the rationale for core outcome sets in atopic dermatitis and review the work of the international Harmonising Outcome Measures for Eczema group from its inception in Munich, 2010. We describe core domain determination (what should be measured), to instrument selection (how domains should be measured), culminating in the complete core outcome measurement set in Tokyo, 2019. Using a "road map," Harmonising Outcome Measures for Eczema includes diverse research methods including Delphi and nominal group techniques informed by systematic reviews of properties of candidate instruments. The 4 domains and recommended instruments for including in all clinical trials of atopic dermatitis are patient symptoms, measured by Patient-Oriented Eczema Measure and peak Numerical Rating Scale 11 for itch intensity over 24 hours, clinical signs measured using the Eczema Area and Severity Index, quality of life measured by the Dermatology Life Quality Index series for adults, children, and infants, and long-term control measured by either Recap of atopic eczema or Atopic Dermatitis Control Tool. Published version Details of funding for each of the consensus meetings is outlined in the published meeting reports. The following additional funding sources contributed to facilitating the HOME COS development: National Institute for Health and Care Research Senior Investigator award to Prof Hywel Williams (RE 2374) funded travel costs to enable UK patients to participate in HOME meetings; National Institute for Health and Care Research Programme Grant for Applied Research RP-PG-0407-10177 ‘‘Setting Priorities and Reducing Uncertainties for the Prevention and Treatment of Skin Disease (SPRUSD)’’ was used to support completion of the some of the systematic reviews, the cost of meetings and patient and public involvement (Prof Kim Thomas); NIH NIAMS A Community-based Assessment of Skin Care, Allergies, and Eczema: The CASCADE Trial grant number 5 R01 AR071057-05 and Oregon Clinical and Translational Research Institute (OCTRI) assisted with outcome evaluations and associated travel costs (Prof Eric Simpson); Laura Howells received a PhD studentship from the British Skin Foundation (Ref: 8016) for studies that informed this work.

Contains fulltext : 251784.pdf (Publisher’s version ) (Closed access) BACKGROUND: Concerns have been raised regarding the risks of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases treated with immunosuppressants, but clinical data on breakthrough infections are still scarce. The primary objective of this study was to compare the incidence and severity of SARS-CoV-2 breakthrough infections between patients with immune-mediated inflammatory diseases using immunosuppressants, and controls (patients with immune-mediated inflammatory diseases not taking immunosuppressants and healthy controls) who had received full COVID-19 vaccinations. The secondary objective was to explore determinants of breakthrough infections of the delta (B.1.617.2) variant of SARS-CoV-2, including humoral immune responses after vaccination. METHODS: In this substudy, we pooled data collected in two large ongoing prospective multicentre cohort studies conducted in the Netherlands (Target to-B! [T2B!] study and Amsterdam Rheumatology Center COVID [ARC-COVID] study). Both studies recruited adult patients (age ≥18 years) with immune-mediated inflammatory diseases and healthy controls. We sourced clinical data from standardised electronic case record forms, digital questionnaires, and medical files. We only included individuals who were vaccinated against SARS-CoV-2. For T2B!, participants were recruited between Feb 2 and Aug 1, 2021, and for ARC-COVID, participants were recruited between April 26, 2020, and March 1, 2021. In this study we assessed data on breakthrough infections collected between July 1 and Dec 15, 2021, a period in which the delta SARS-CoV-2 variant was the dominant variant in the Netherlands. We defined a SARS-CoV-2 breakthrough infection as a PCR-confirmed or antigen test-confirmed SARS-CoV-2 infection that occurred at least 14 days after vaccination. All breakthrough infections during this period were assumed to be due to the delta variant due to its dominance during the study period. We analysed post-vaccination serum samples for anti-receptor binding domain (RBD) antibodies to assess the humoral vaccination response (T2B! study only) and anti-nucleocapsid antibodies to identify asymptomatic breakthrough infections (ARC-COVID study only). We used multivariable logistic regression analyses to explore potential clinical and humoral determinants associated with the odds of breakthrough infections. The T2B! study is registered with the Dutch Trial Register, Trial ID NL8900, and the ARC-COVID study is registered with Dutch Trial Register, trial ID NL8513. FINDINGS: We included 3207 patients with immune-mediated inflammatory diseases who receive immunosuppressants, and 1807 controls (985 patients with immune-mediated inflammatory disease not on immunosuppressants and 822 healthy controls). Among patients receiving immunosuppressants, mean age was 53 years (SD 14), 2042 (64%) of 3207 were female and 1165 (36%) were male; among patients not receiving immunosuppressants, mean age was 54 years (SD 14), 598 (61%) of 985 were female and 387 (39%) were male; and among healthy controls, mean age was 57 years (SD 13), 549 (67%) of 822 were female and 273 (33%) were male. The cumulative incidence of PCR-test or antigen-test confirmed SARS-CoV-2 breakthrough infections was similar in patients on immunosuppressants (148 of 3207; 4·6% [95% CI 3·9-5·4]), patients not on immunosuppressants (52 of 985; 5·3% [95% CI 4·0-6·9]), and healthy controls (33 of 822; 4·0% [95% CI 2·8-5·6]). There was no difference in the odds of breakthrough infection for patients with immune-mediate inflammatory disease on immunosuppressants versus combined controls (ie, patients not on immunosuppressants and healthy controls; adjusted odds ratio 0·88 [95% CI 0·66-1·18]). Seroconversion after vaccination (odds ratio 0·58 [95% CI 0·34-0·98]; T2B! cohort only) and SARS-CoV-2 infection before vaccination (0·34 [0·18-0·56]) were associated with a lower odds of breakthrough infections. INTERPRETATION: The incidence and severity of SARS-CoV-2 breakthrough infections in patients with immune-mediated inflammatory diseases on immunosuppressants was similar to that in controls. However, caution might still be warranted for those on anti-CD20 therapy and those with traditional risk factors. FUNDING: ZonMw (the Netherlands Organization for Health Research and Development) and Reade foundation.

Importance: Systemic treatments for atopic dermatitis are being evaluated primarily in placebo-controlled trials; network meta-analysis can provide relative efficacy and safety estimates for treatments that have not been compared head to head.Objective: To compare reported measures of efficacy and assessments of safety in clinical trials of systemic treatments for atopic dermatitis in a living systematic review and network meta-analysis.Data Sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of EczemA Trials database, and trial registries were searched through June 15, 2021.Study Selection: Randomized clinical trials examining 8 or more weeks of treatment with systemic immunomodulatory medications for moderate-to-severe atopic dermatitis were included after screening titles, abstracts, and papers in duplicate.Data Extraction and Synthesis: Data were abstracted in duplicate. Bayesian network meta-analyses and assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed. The updated analysis was completed from June to December 2021.Main Outcomes and Measures: Outcomes include change in Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS).Results: Since October 2019, 21 new studies were added, for a total of 60 trials with 16 579 patients. Up to 16 weeks of treatment in adults, abrocitinib, 200 mg daily (mean difference [MD], 2.2; 95% credible interval [CrI], 0.2-4.0; high certainty) and upadacitinib, 30 mg daily (MD, 2.7; 95% CrI, 0.6-4.7; high certainty) were associated with reduced EASI slightly more than dupilumab, 600 mg then 300 mg every 2 weeks. Abrocitinib, 100 mg daily (MD, -2.1; 95% CrI, -4.1 to -0.3; high certainty), baricitinib, 4 mg daily (MD, -3.2; 95% CrI, -5.7 to -0.8; high certainty), baricitinib, 2 mg daily (MD, -5.2; 95% CrI, -7.5 to -2.9; high certainty) and tralokinumab, 600 mg then 300 mg every 2 weeks (MD, -3.5; 95% CrI, -5.8 to -1.3; high certainty) were associated with reduced EASI slightly less than dupilumab. There was little or no difference between upadacitinib, 15 mg daily, and dupilumab (MD, 0.2; 95% CrI, -1.9 to 2.2; high certainty). The pattern of results was similar for POEM, DLQI, and PP-NRS.Conclusions and Relevance: In this systematic review and meta-analysis, abrocitinib, 200 mg; and upadacitinib, 30 mg daily, were associated with slightly better scores than dupilumab, and upadacitinib, 15 mg daily, was associated with similar scores to dupilumab. Abrocitinib, 100 mg daily, baricitinib, 4 mg and 2 mg daily, and tralokinumab, 300 mg, every 2 weeks were associated with slightly worse scores.

Background: Anti-drug antibodies (ADA) are formed in patients treated with adalimumab (ADL). This might increase clearance of ADL, potentially causing a (secondary) non-response. Combination therapy of ADL and methotrexate (MTX) reduces ADA levels and has a clinical benefit in rheumatologic diseases. In psoriasis however, the long-term effectiveness and safety have not been studied. Objectives: To investigate the three-year follow-up data of ADL combined with MTX compared to ADL monotherapy in ADL-naive patients with moderate to severe plaque type psoriasis. Methods: We conducted a multicentre RCT in the Netherlands and Belgium. Randomization was performed by a centralized online randomization service. Patients were seen every 12 weeks until week 145. Outcome assessors were blinded. We collected data on drug survival, effectiveness, safety, pharmacokinetics and immunogenicity of patients that started ADL combined with MTX compared to ADL monotherapy. We present descriptive analysis and patients were analysed according to the group initially randomized to. Patients becoming non-adherent to the biologic were excluded from analyses. Results: Sixty-one patients were included and 37 patients (ADL group n = 17, ADL + MTX group n = 20) continued in the follow-up study after 1 year. After 109 weeks and 145 weeks, there was a trend towards longer drug survival in the ADL + MTX group compared to the ADL group (week 109: 54.8% vs. 41.4%; p = 0.326, week 145: 51.6% vs. 41.4%; p = 0.464). At week 145, 7/13 patients were treated with MTX. In the ADL group, 4/12 patients that completed the study developed ADA, and 3/13 in the ADL + MTX group. Conclusions: In this small study, there was no significant difference in ADL overall drug survival when it was initially combined with MTX, compared to ADL alone. Discontinuation due to adverse events was common in the combination group. To secure accessible healthcare, combination treatment of ADL and MTX can be considered in individual patients.

Background: Methotrexate (MTX) is a systemic treatment for plaque-type psoriasis. At the time of approval, no dose-ranging studies were performed. Nowadays, a uniform dosing regimen is lacking. This might contribute to suboptimal treatment with the drug. Objective: To summarize the literature involving the MTX dosing regimens in psoriasis patients. Methods: In this SR, RCTs and documents with aggregated evidence (AgEv) on the MTX dosing regimen in psoriasis were summarized. All randomized controlled trials (RCTs) in which oral, subcutaneous or intramuscular MTX was used in patients with psoriasis and AgEv, were included. The MEDLINE, EMBASE and CENTRAL databases were searched up to June 20, 2022. This SR was registered in PROSPERO. Results: Thirty-nine RCTs had a high risk of bias. Test dosages were given in only 3 RCTs. In the RCTs, MTX was usually prescribed in a start dose of 7.5 mg/week (n = 13). MTX was mostly given in a start dose of 15 mg/week, in the AgEv (n = 5). One guideline recommended a test dose, in other aggregated evidence a test dose was not mentioned or even discouraged. Conclusions: There is a lack of high-quality evidence and available data for dosing MTX in psoriasis is heterogeneous.

During the COVID-19 pandemic, rapid, real-world evidence is essential for the development of knowledge and subsequent public health response. In dermatology, provider-facing and patient-facing registries focused on COVID-19 have been important sources of research and new information aimed at guiding optimal patient care. The 7 dermatology registries included in this update now include more than 8000 case reports sourced from physicians and patients from countries all over the world.

Background For immunocompromised patients (ICPs), administration of rabies immunoglobulins (RIG) after exposure is still recommended regardless of prior vaccination, due to a lack of data. We aimed to assess the 1-year boostability of a three-dose rabies pre-exposure prophylaxis (PrEP) schedule in individuals using immunosuppressive monotherapy. Methods In this prospective study, individuals on immunosuppressive monotherapy with a conventional immunomodulator (cIM) or a TNF-alpha inhibitor (TNFi) for a chronic inflammatory disease received a three-dose intramuscular PrEP schedule (days 0,7,21–28) with 1 mL Rabipur®, followed by a two-dose simulated post-exposure prophylaxis (PEP) schedule (days 0,3) after 12 months. Rabies neutralizing antibodies were assessed at baseline, on day 21–28 (before the third PrEP dose), day 60, month 12 and month 12 + 7 days. The primary outcome was 1-year boostability, defined as the proportion of patients with a neutralizing antibody titre of ≥ 0.5 IU/mL at month 12 + 7 days. Secondary outcomes were geometric mean titres (GMTs) and factors associated with the primary endpoint. Results We included 56 individuals, of whom 52 completed the study. The 1-year boostability was 90% (47/52) with a GMT of 6.16 (95% CI 3.83–9.91). All participants seroconverted at some point in the study. Early response to PrEP (at day 21–28) was significantly associated with 100% boostability (Odds Ratio 51; 95% confidence interval [5.0–6956], P Conclusion In patients using immunosuppressive monotherapy, a three-dose rabies PrEP schedule followed by a two-dose PEP schedule is immunogenic, with all patients seroconverting at some point in the study. Although boostability 7 days after PEP was not 100%, nobody would wrongly be denied RIG when only administered to those who responded early to PrEP while reducing the administration of RIG by 73%.

Background: few data exist on differences in treatment effectiveness and safety in atopic dermatitis patients of different skin types.Objective: to investigate treatment outcomes of dupilumab, methotrexate, and ciclosporin, and morphological phenotypes in atopic dermatitis patients, stratified by Fitzpatrick skin type.Methods: in an observational prospective cohort study, pooling data from the Dutch TREAT (TREatment of ATopic eczema) NL (treatregister.nl) and UK-Irish A-STAR (Atopic eczema Systemic TherApy Register; astar-register.org) registries, data on morphological phenotypes and treatment outcomes were investigated.Results: a total of 235 patients were included (light skin types [LST]: Fitzpatrick skin type 1-3, n = 156 [Ethnicity, White: 94.2%]; dark skin types [DST]: skin type 4-6, n = 68 [Black African/Afro-Caribbean: 25%, South-Asian: 26.5%, and Hispanics: 0%]). DST were younger (19.5 vs 29.0 years; P < .001), more often had follicular eczema (22.1% vs 2.6%; P < .001), higher baseline Eczema Area and Severity Index (EASI) scores (20.1 vs 14.9; P = .009), less allergic contact dermatitis (30.9% vs 47.4%; P = .03), and less previous phototherapy use (39.7% vs 59.0%; P = .008). When comparing DST and LST corrected for covariates including baseline EASI, DST showed greater mean EASI reduction between baseline and 6 months with only dupilumab (16.7 vs 9.7; adjusted P = .032). No differences were found for adverse events for any treatments (P > .05).Limitations: unblinded, non-randomized.Conclusions: atopic dermatitis differs in several characteristics between LST and DST. Skin type may influence treatment effectiveness of dupilumab.

OBJECTIVES: Patient-reported outcomes (PROs) are increasingly used in studies and medical practice to obtain information on patients' perspectives toward their treatment or disease. However, most study outcomes are primarily directed at healthcare professionals. It was aimed to obtain insight in which type of information immune-mediated inflammatory disease (IMID) patients prefer to receive after participating in the Dutch Biologic Monitor (DBM), a PRO-based prospective cohort event monitoring system focused on adverse drug reactions (ADRs).METHODS: A survey was conducted among DBM participants that wanted information about the results. Patients' preferences were identified using twelve statements and rated with five-point Likert-type scales. Subgroup analyses and differences between statements were performed using Mann-Whitney U Tests.RESULTS: The survey was completed by 591 patients (response rate 67.6%). Most respondents had inflammatory rheumatic diseases (76.8%) and used adalimumab (37.2%) or etanercept (33.2%). Respondents preferred results per IMID over aggregated results (p = CONCLUSION: DBM participants prefer to receive disease-specific information on ADRs that is tailored to their own biologic and IMID, including the outcome of ADRs.

Background: Measuring patient-centered outcomes in clinical practice is valuable for monitoring patients and advancing real-world research. A new initiative from the Harmonising Outcome Measures for Eczema (HOME) group aims to recommend what might be recorded for atopic eczema patients in routine clinical care. Objectives: Prioritize outcome domains to measure atopic eczema in clinical practice and select valid and practical outcome measurement instruments for the highest-priority domain. Methods: An online survey of HOME members identified and ranked 21 possible health domains. Suitable instruments were then selected for the top-prioritized domain at the HOME VI meeting, using established consensus processes informed by systematic reviews of instrument quality. Results: Patient-reported symptoms was the top-prioritized domain. In accordance with psychometric properties and feasibility, there was consensus that the recommended instruments to measure atopic eczema symptoms in clinical practice are the POEM, the PO-SCORAD index, or both. The numeric rating scale for itch received support pending definition and validation in atopic eczema. Conclusion: Following the first step of the HOME Clinical Practice initiative, we endorse using the POEM, the PO-SCORAD index, or both for measuring atopic eczema symptoms in clinical practice. Additional high-priority domains for clinical practice will be assessed at subsequent HOME meetings.

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 1.71-14.78]), including after adjustment for confounding variables (adjusted OR (aOR) 4.99 [95%CI 1.4-20.84]). 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 0.4-59.96], aOR 37.57 [95%CI 1.05-871.11]). Hospitalization was most likely in patients treated with combination systemic therapy which included systemic corticosteroids (OR 40.43 [95%CI 8.16-207.49], aOR 45.75 [95%CI 4.54-616.22]).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.

Background: Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders treated with specific immunosuppressants. Disease-overarching studies, and data on recall responses and third vaccinations are scarce. Our primary objective was to investigate the effects of immunosuppressive monotherapies on the humoral immune response after SARS-CoV-2 vaccination in patients with prevalent immune-mediated inflammatory disorders.Methods: We did a cohort study in participants treated in outpatient clinics in seven university hospitals and one rheumatology treatment centre in the Netherlands as well as participants included in two national cohort studies on COVID-19-related disease severity. We included patients aged older than 18 years, diagnosed with any of the prespecified immune-mediated inflammatory disorders, who were able to understand and complete questionnaires in Dutch. Participants with immune-mediated inflammatory disorders who were not on systemic immunosuppressants and healthy participants were included as controls. Anti-receptor binding domain IgG responses and neutralisation capacity were monitored following standard vaccination regimens and a three-vaccination regimen in subgroups. Hybrid immune responses-ie, vaccination after previous SARS-CoV-2 infection-were studied as a proxy for recall responses.Findings: Between Feb 2 and Aug 1, 2021, we included 3222 participants in our cohort. Sera from 2339 participants, 1869 without and 470 participants with previous SARS-CoV-2 infection were analysed (mean age 49·9 years [SD 13·7]; 1470 [62·8%] females and 869 [37·2%] males). Humoral responses did not differ between disorders. Anti-CD20 therapy, sphingosine 1-phosphate receptor (S1P) modulators, and mycophenolate mofetil combined with corticosteroids were associated with lower relative risks for reaching seroconversion following standard vaccination (0·32 [95% CI 0·19-0·49] for anti-CD20 therapy, 0·35 [0·21-0·55] for S1P modulators, and 0·61 [0·40-0·90] for mycophenolate mofetil combined with corticosteroids). A third vaccination increased seroconversion for mycophenolate mofetil combination treatments (from 52·6% after the second vaccination to 89·5% after the third) but not significantly for anti-CD20 therapies (from 36·8% to 45·6%) and S1P modulators (from 35·5% to 48·4%). Most other immunosuppressant groups showed moderately reduced antibody titres after standard vaccination that did not increase after a third vaccination, although seroconversion rates and neutralisation capacity were unaffected. In participants with previous SARS-CoV-2 infection, SARS-CoV-2 antibodies were boosted after vaccination, regardless of immunosuppressive treatment.Interpretation: Humoral responses following vaccination are impaired by specific immunosuppressants. After standard vaccination regimens, patients with immune-mediated inflammatory disorders taking most immunosuppressants show similar seroconversion to controls, although antibody titres might be moderately reduced. As neutralisation capacity and recall responses are also preserved in these patients, this is not likely to translate to loss of (short-term) protection. In patients on immunosuppressants showing poor humoral responses after standard vaccination regimens, a third vaccination resulted in additional seroconversion in patients taking mycophenolate mofetil combination treatments, whereas the effect of a third vaccination in patients on anti-CD20 therapy and S1P modulators was limited.Funding: ZonMw (The Netherlands Organization for Health Research and Development).

Item does not contain fulltext BACKGROUND: We aimed to investigate course and burden over time of ADRs attributed to TNFα-inhibitors in IRD-patients, and whether Sankey diagrams and polar plots can visualize this. RESEARCH DESIGN AND METHODS: Data on ADRs experienced during the Dutch Biologic Monitor (January 2017 till December 2022) were used in this study. We selected IRD-patients using a TNFα-inhibitor, reporting skin reactions/infections/injection site reactions and completing ≥3 questionnaires (i.e. the initial report and ≥2 follow-ups). Course was scored as worsening/improving/remaining stable/resolving and as (non-)recurrent. Patients scored burden from 1 (no burden) to 5 (very high burden). Sankey diagrams and polar plots visualized this. RESULTS: 202 patients were included, reporting 353 ADRs. Most skin reactions were stable (25.0%). Most infections resolved (50.8%). Injection site reactions were mostly recurrent (72.3%). Skin reactions and infections tended to decrease in burden . Infections had highest burden at start, which mostly decreased over time. Injection site reactions had a low and stable burden. CONCLUSIONS: Skin reactions attributed to TNFα-inhibitors by IRD-patients are stable with a slightly decreasing burden over time. Infections have highest burden at start but resolved mostly. Injection site reactions have a low and stable burden. Sankey diagrams and polar plots are suitable to visualize this.

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 physician-assessed signs and patient-reported symptoms. Secondary outcomes were Investigator Global Assessment (IGA), health-related quality of life (HRQoL), safety (measured as withdrawals due to adverse events), and long-term 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 (NB-UVB; 13 trials), ultraviolet A1 (UVA1; 6 trials), broadband ultraviolet B (BB-UVB; 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): NB-UVB versus placebo/no treatment There may be a larger reduction in physician-assessed signs with NB-UVB compared to placebo after 12 weeks of treatment (mean difference (MD) -9.4, 95% confidence interval (CI) -3.62 to -15.18; 1 trial, 41 participants; scale: 0 to 90). Two trials reported little difference between NB-UVB and no treatment (37 participants, four to six weeks of treatment); another reported improved signs with NB-UVB versus no treatment (11 participants, nine weeks of treatment). NB-UVB 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 NB-UVB (25 participants, four weeks of treatment). The number of participants with moderate to greater global improvement may be higher with NB-UVB than placebo after 12 weeks of treatment (RR 2.81, 95% CI 1.10 to 7.17; 1 trial, 41 participants). NB-UVB may not affect rates of withdrawal due to adverse events. No withdrawals were reported in one trial of NB-UVB versus placebo (18 participants, nine weeks of treatment). In two trials of NB-UVB 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 low-certainty evidence, due to risk of bias and imprecision. No trials reported HRQoL. NB-UVB versus UVA1 We judged the evidence for NB-UVB 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 physician-assessed signs after six weeks (MD -2.00, 95% CI -8.41 to 4.41; 1 trial, 46 participants; scale: 0 to 108), or patient-reported itch after six weeks (MD 0.3, 95% CI -1.07 to 1.67; 1 trial, 46 participants; scale: 0 to 10). Two split-body trials (20 participants, 40 sides) also measured these outcomes, using different scales at seven to eight weeks; they reported lower scores with NB-UVB. One trial reported HRQoL at six weeks (MD 2.9, 95% CI -9.57 to 15.37; 1 trial, 46 participants; scale: 30 to 150). One split-body trial reported no withdrawals due to adverse events over 12 weeks (13 participants). No trials reported IGA. NB-UVB versus PUVA We judged the evidence for NB-UVB compared to PUVA (8-methoxypsoralen 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 physician-assessed signs after six weeks (64.1% reduction with NB-UVB 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 split-body trial reported no withdrawals due to adverse events in 10 participants over six weeks. The trials did not report patient-reported symptoms or HRQoL. UVA1 versus PUVA There was very low-certainty evidence, due to serious risk of bias and imprecision, that PUVA (oral 5-methoxypsoralen plus UVA) reduced physician-assessed signs more than UVA1 after three weeks (MD 11.3, 95% CI -0.21 to 22.81; 1 trial, 40 participants; scale: 0 to 103). The trial did not report patient-reported 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, NB-UVB may improve physician-rated signs, patient-reported symptoms, and IGA after 12 weeks, without a difference in withdrawal due to adverse events. Evidence for UVA1 compared to NB-UVB or PUVA, and NB-UVB compared to PUVA was very low certainty. More information is needed on the safety and effectiveness of all aspects of phototherapy for treating AE.

Background: Evidence on long-term dupilumab treatment for atopic dermatitis in daily practice is lacking. Objective: To investigate patient characteristics, treatment aspects, effectiveness, and safety of up to 84 weeks of dupilumab treatment. Methods: An observational prospective cohort study was conducted of patients with atopic dermatitis starting dupilumab in routine clinical care. Results: Of the 221 included patients, 103 used systemic therapy at baseline. At 84 weeks, we found a change of −15.2 (SE, 1.7) for the Eczema Area and Severity Index, −16.9 (SE, 1.4) for the Patient-Oriented Eczema Measure, and −17.2 (SE, 1.6) for the Dermatology Life Quality Index. We found a trend for improvement over time for the Investigator Global Assessment and Numerical Rating Scale for pruritus. Severe (n = 79) including serious (n = 11) adverse events were observed in 69 patients. Eye complaints were most frequently reported (n = 46). Twenty-one patients adjusted the regular dosing schedule, and 14 patients discontinued treatment, mainly due to ineffectiveness (n = 7). Limitations: Only adverse events of severe and serious nature were registered for feasibility reasons. Conclusion: Daily practice dupilumab treatment of up to 84 weeks is generally well-tolerated, apart from the reporting of eye complaints. It can be considered a long-term effective treatment for atopic dermatitis in combination with topical and initial concomitant systemic treatment, showing a sustained improvement of signs, symptoms, and quality of life.

ObjectiveWe aimed to describe the nature and frequency of gastrointestinal adverse drug reactions (GI-ADRs) of etanercept (ETN) using patient-reported and healthcare professional (HCP)-registered data and compared this frequency with the GI-ADR frequency of the widely used tumor necrosis factor-α inhibitor adalimumab (ADA).MethodsReported GI-ADRs of ETN for rheumatic diseases were collected from the Dutch Biologic Monitor and DREAM registries. We described the clinical course of GI-ADRs and compared the frequency with ADA in both data sources using Fisher exact test.ResultsOut of 416 patients using ETN for inflammatory rheumatic diseases in the Dutch Biologic Monitor, 25 (6%) patients reported 36 GI-ADRs. In the DREAM registries 11 GI-ADRs were registered for 9 patients (2.3%), out of 399 patients using ETN, with an incidence of 7.1 per 1000 patient-years. Most GI-ADRs consisted of diarrhea, nausea, and abdominal pain. GI-ADRs led to ETN discontinuation in 1 patient (4%) and dose adjustment in 4 (16%) in the Dutch Biologic Monitor. Eight GI-ADRs (73%) led to ETN discontinuation in the DREAM registries. The frequency of GI-ADRs of ETN did not significantly differ from GI-ADRs of ADA in both data sources (Dutch Biologic Monitor: ETN 8.7% vs ADA 5.3%, P = 0.07; DREAM: ETN 2.8% vs ADA 4.7%, P = 0.16).ConclusionMost GI-ADRs associated with ETN concerned gastrointestinal symptoms. These ADRs may lead to dose adjustment or ETN discontinuation. The frequency of ETN-associated GI-ADRs was comparable to the frequency of ADA-associated GI-ADRs. Knowledge about these previously unknown ADRs can facilitate early recognition and improve patient communication.

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.

Background The multi-morbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse COVID-19 outcomes but data are limited. Objective Characterize the course of COVID-19 in psoriasis and identify factors associated with hospitalization. Methods Clinicians reported psoriasis patients with confirmed/suspected COVID-19 via an international registry, PsoProtect. Multiple logistic regression assessed the association between clinical/demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviours. Results Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% a non-biologic and 10% no systemic treatment for psoriasis. 348 (93%) fully recovered from COVID-19, 77 (21%) were hospitalized and nine (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted OR 1.59 per 10 years, 95% CI 1.19-2.13), male sex (OR 2.51, 95% CI 1.23-5.12), non-white ethnicity (OR 3.15, 95% CI 1.24-8.03) and comorbid chronic lung disease (OR 3.87, 95% CI 1.52-9.83). Hospitalization was more frequent in patients using non-biologic systemic therapy than biologics (OR 2.84, 95% CI 1.31-6.18). No significant differences were found between biologic classes. Independent patient-reported data (n=1,626 across 48 countries) suggested lower levels of social isolation in individuals receiving non-biologic systemic therapy compared to biologics (OR 0.68, 95% CI 0.50-0.94). Conclusion In this international moderate-severe psoriasis case series, biologics use was associated with lower risk of COVID-19-related hospitalization than non-biologic systemic therapies, however further investigation is warranted due to potential selection bias and unmeasured confounding. Established risk factors (being older, male, non-white ethnicity, comorbidities) were associated with higher hospitalization rates. Clinical Implications We identify risk factors for COVID-19-related hospitalization in psoriasis patients, including older age, male sex, non-white ethnicity and comorbidities. Use of biologics was associated with lower hospitalization risk than non-biologic systemic therapies., Capsule summary: In this global registry-based study, risk factors for COVID-19-related hospitalization in psoriasis patients were older age, male sex, non-white ethnicity and comorbidities. Use of biologics was associated with lower hospitalization risk than non-biologic systemic treatment.

Contains fulltext : 244669.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patient-reported outcomes (PROs) on adverse drug reactions (ADRs) are increasingly used in cohort event monitoring (CEM) to obtain a better understanding of patients' real-world experience with drugs. Despite the leading role for patients, little is known about their perspectives on CEM systems. RESEARCH DESIGN AND METHODS: In a cross-sectional open survey following the rationale of the Technology Acceptance Model, we aimed to obtain insight in patients' perspectives on the perceived usefulness, ease of use and attitude toward using a PRO-based drug safety monitoring system for ADRs attributed to biologics. RESULTS: Patients considered structural reporting of ADRs in web-based questionnaires as useful and not burdensome. It was preferred to link the questionnaire frequency to regular hospital consultations or the biologic administration schedule. Various respondents were interested in sharing questionnaires with their medical specialist (49.0%) or pharmacist (34.2%), and suggested to minimize the questionnaire frequency in case of an unaltered situation or absence of ADRs. CONCLUSIONS: Patients' perspectives should be considered in the setup of PRO-based CEM studies, as this contributes to data quality and patient centeredness. Since incorporation of patients' perspectives in CEM studies is indispensable, a delicate balance should be found between user-friendliness and study aims.

If an authorized drug is prescribed for a use that is not described in the Summary of Product Characteristics, this is defined as 'off-label use.' Methotrexate is often used off-label for dermatological indications. Off-label use is permitted if physicians can justify the treatment based on scientific evidence available to them. Our objective here was therefore to summarize the evidence for the effectiveness, efficacy, and safety of the dermatological off-label use of methotrexate in a systematic review. We searched MEDLINE, EMBASE, and CENTRAL for studies for evidence on the effectiveness, efficacy, and safety of the off-label use of methotrexate in dermatological indications up to November 2019. We used the GRADE system to rate the quality of the evidence. The search retrieved 34,583 hits of which 3566 were selected after the title and abstract screening. After the full-text screening, 143 studies were included, which involved 3688 patients in total. We found low-quality evidence for the effectiveness, efficacy, and safety of the off-label use of methotrexate in 31 dermatological diseases. To optimize the quality of evidence to support off-label use, we need high-quality studies in which well-characterized patients are treated with standardized treatments regimens using well-validated outcomes relevant to patients and physicians.

SUMMARYBackgroundAtopic dermatitis (AD or eczema) is a most common chronic skin disease. Designing personalised treatment strategies for AD based on patient stratification, rather than the “one-size-fits-all” treatments, is of high clinical relevance. It has been hypothesised that the measurement of biomarkers could help predict therapeutic response for individual patients.ObjectiveWe aim to assess whether biomarkers can predict the outcome of systemic therapy.MethodsWe developed a statistical machine learning predictive model using the data of an already published longitudinal study of 42 patients who received systemic therapy. The data contained 26 serum cytokines measured before the therapy. The model described the dynamics of the latent disease severity and measurement errors to predict AD severity scores (EASI, (o)SCORAD and POEM) two-weeks ahead. We conducted feature selection to identify the most important biomarkers for predicting the AD severity scores.ResultsWe validated our model and confirmed that it outperformed standard time-series forecasting models. Adding biomarkers did not improve predictive performance. Our estimates of the minimum detectable change for the AD severity scores were larger than already published estimates of the minimal clinically important difference.ConclusionsBiomarkers had a negligible and non-significant effect for predicting the future AD severity scores and the outcome of the systemic therapy. Instead, a historical record of severity scores provides rich and insightful dynamical information required for prediction of therapeutic responses.

In shared decision making (SDM) patients and physi-cians make treatment decisions together based on the best available evidence and the values and preferences of patients. SDM is very suitable for use in dermatological practice, but is infrequently applied by dermatologists. To support the application of SDM in dermatology we developed Decision Cards: 1-page overviews of possible treatment options, for use during a patient-physician consultation. Decision Cards provide answers to patients' most frequently asked questions, based on (inter)national guidelines, Summary of Product Characteristics, relevant literature, and clinical expertise. Three evidence-based Decision Cards were developed: 1 for biologicals or apremilast in psoriasis, and 2 for atopic eczema (1 for topical, photo- or systemic therapy, and 1 for systemic therapy only). More cards for psoriasis are currently in development. Patients, dermatologists and researchers collaborated in the development of the Decision Cards. This paper shares the framework used for the development of the Decision Cards, in order to support others in the development process.

Summary Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey‐coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD – cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy – overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site‐ and skin‐type‐specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is to present the latest evidence from animal and human studies, including recent microbiome research, to define the clinical features of bacterial infections in AD, and to summarize our current understanding of the host and bacterial factors that influence microbial colonization and virulence.

Critically appraised topics (CATs) are essential tools for busy clinicians who wish to ensure that their daily clinical practice is underpinned by evidence-based medicine. CATs are short summaries of the most up-to-date, high-quality available evidence that is found using thorough structured methods. They can be used to answer specific, patient-orientated questions that arise recurrently in real-life practice. This article provides readers with a detailed guide to performing their own CATs. It is split into four main sections reflecting the four main steps involved in performing a CAT: formulation of a focused question, a search for the most relevant and highest-quality evidence, critical appraisal of the evidence and application of the results back to the patient scenario. As well as helping to improve patient care on an individual basis by answering specific clinical questions that arise, CATs can help spread and share knowledge with colleagues on an international level through publication in the evidence-based dermatology section of the British Journal of Dermatology.

Importance: Most clinical trials assessing systemic immunomodulatory treatments for patients with atopic dermatitis are placebo-controlled.Objective: To compare the effectiveness and safety of systemic immunomodulatory treatments for patients with atopic dermatitis in a systematic review and network meta-analysis.Data Sources: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of Eczema Trials database, and clinical trial registries were searched from inception to October 28, 2019.Study Selection: English-language randomized clinical trials of 8 weeks or more of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis were included. Titles, abstracts, and articles were screened in duplicate. Of 10 324 citations, 39 trials were included.Data Extraction and Synthesis: Data were extracted in duplicate, and the review adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-Analyses guidelines. Random-effects bayesian network meta-analyses were performed and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria.Main Outcomes and Measures: Prespecified outcomes were change in signs of disease, symptoms, quality of life, itch, withdrawals, and serious adverse events.Results: A total of 39 trials with 6360 patients examining 20 medications and placebo were included. Most trials were conducted for adults receiving up to 16 weeks of therapy. Dupilumab, 300 mg every 2 weeks, was associated with improvement in the Eczema Area and Severity Index score vs placebo (mean difference, 11.3-point reduction; 95% credible interval [CrI], 9.7-13.1 [high certainty]). Cyclosporine (standardized mean difference, -1.1; 95% CrI, -1.7 to -0.5 [low certainty]) and dupilumab (standardized mean difference, -0.9; 95% CrI, -1.0 to -0.8 [high certainty]) were similarly effective vs placebo in clearing clinical signs of atopic dermatitis and may be superior to methotrexate (standardized mean difference, -0.6; 95% CrI, -1.1 to 0.0 [low certainty]) and azathioprine (standardized mean difference, -0.4; 95% CrI, -0.8 to -0.1 [low certainty]). Several investigational medications for atopic dermatitis are promising, but data to date are limited to small early-phase trials. Safety analyses were limited by low event rates.Conclusions and Relevance: Dupilumab and cyclosporine may be more effective for up to 16 weeks of treatment than methotrexate and azathioprine for treating adult patients with atopic dermatitis. More studies directly comparing established and novel treatments beyond 16 weeks are needed and will be incorporated into future updates of this review.

Background Dupilumab is the first biologic registered for the treatment of moderate-to-severe atopic dermatitis (AD), and efficacy was shown in phase III clinical trials (primary outcome at week 16 was reached in 38% of patients). Currently, there are limited daily practice data available for dupilumab, especially when it is combined with systemic immunosuppressants. Objectives To evaluate dupilumab treatment in daily practice in patients with AD. Methods In this observational cohort study, we prospectively included all adult patients with AD who had been treated with dupilumab in two university hospitals in the Netherlands. Concomitant systemic immunosuppressive treatment was monitored. Physician-reported outcome measures and patient-reported outcome measures (PROMs) after ≥ 12 weeks of follow-up were analysed. We used a linear mixed-effects model to determine changes in scores during follow-up. Results Ninety-five patients were included. Of these, 62 patients were using systemic immunosuppressants at baseline; the use of systemic immunosuppressants was continued during dupilumab treatment in 43 patients. From baseline to 16 weeks of treatment, the estimated mean Eczema Area and Severity Index score (0-72) decreased from 18·6 [95% confidence interval (CI) 16·0-21·4)] to 7·3 (95% CI 5·4-10·0), and the estimated mean PROMs showed a decrease of 41-66%. Investigator's Global Assessment 0 or 1 (clear/almost clear) was reached in 38% of the patients. Five patients discontinued dupilumab treatment due to side-effects or ineffectiveness. Eye symptoms and orofacial (nonocular) herpes simplex virus (HSV) reactivation were reported in 62% and 8% of the patients, respectively. Conclusions Dupilumab treatment in daily practice shows a clinically relevant improvement of physician-reported outcome measures and PROMs, which is in line with efficacy data from clinical trials. Besides frequently reported eye symptoms and orofacial (nonocular) HSV reactivation, there were no apparent safety concerns. What's already known about this topic? Dupilumab has been shown to be an efficacious treatment for atopic dermatitis in several clinical trials. However, it is known that there may be considerable differences in patient characteristics and treatment responses between clinical trials and daily practice. What does this study add? This study presents the first experience with dupilumab treatment in 95 patients with atopic dermatitis in daily practice in two Dutch university hospitals. Less stringent inclusion and exclusion criteria and follow-up schedules, in contrast to those used in clinical trials, might better represent daily practice. Dupilumab treatment shows a clinically relevant improvement of physician- and patient-reported outcome measures; besides patient-reported eye symptoms (in 59 of 95 patients; 62%) and an apparent increase in orofacial (nonocular) herpes simplex virus reactivation (eight of 95 patients; 8%), there were no other safety concerns during follow-up up to 16 weeks of dupilumab treatment.

International audience; Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.

Background:Patient-reported outcomes (PROs) on adverse drug reactions (ADRs) are increasingly used in cohort event monitoring (CEM) to obtain a better understanding of patient’s real-world experience with drugs. Despite the leading role for patients, little is known about their perspectives on these monitoring systems.Objectives:To obtain more insight in patients’ perspectives on the perceived usefulness, ease of use and attitude toward using the Dutch Biologic Monitor (DBM), and their preferred design for a national drug safety monitoring system for immune-mediated inflammatory diseases (IMIDs).Methods:We developed a cross-sectional open survey following the rationale of the Technology Acceptance Model to obtain insight in patients’ perspectives on the DBM. The DBM is a pilot for a PRO-based drug safety monitoring system focused on ADRs attributed to biologics that are prescribed for IMIDs. This survey consisted of 20 categorical and 1 open-ended question. Seven categorical questions contained a text field for additional comments. Five-point Likert-type scales or multiple-choice questions were used to identify patients’ preferences and perspectives. Patients were eligible for the survey if they were still enrolled in the DBM at the time of the survey opening and if they had completed at least one questionnaire of the DBM. Categorical questions were descriptively analyzed, whereas text fields were analyzed using theoretical thematic analysis.Results:At the start of the survey a total of 1,225 patients had participated in the DBM. Approximately 70% had an inflammatory rheumatic disease. The survey was completed by 292 eligible respondents (response rate 44.8%). The respondents generally agreed that it was useful to participate in the DBM and would recommend it to their peers (Figure 1). The response burden of the bimonthly questionnaires was scored as ‘low’, irrespective of the presence of ADRs or education level (Table 1). A number of respondents suggested that the questionnaire frequency should be synchronized with the regular hospital visits or the administration schedule of the biologic. Moreover, questionnaires should be offered less frequent and preferably shortened in case of an unaltered situation or absence of ADRs. Half (49.0%) of the respondents was interested in sharing their questionnaires with a medical specialist, whereas a third (34.2%) advocated sharing the questionnaires with their pharmacist (Figure 1).Table 1.Perceived response burden of the Dutch Biologic Monitor questionnaires. The average burden is calculated using a five-point Likert-type scale. Data is represented as the number of respondents (n).Overall(n = 292)ADRs reportedEducation levelaYes(n = 225)No(n = 54)Do not know(n = 13)Lower(n = 149)Higher(n = 139)Burdenn(%)n(%)n(%)n(%)n(%)n(%)1: No burden224(76.7)169(75.1)46(85.2)9(69.2)106(71.1)115(82.7)2: Low burden58(19.9)48(21.3)7(13.0)3(23.1)36(24.2)22(15.8)3: Moderate burden6(2.1)6(2.7)0(0.0)0(0.0)4(2.7)2(1.4)4: High burden0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)5: Very high burden0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)0(0.0)No opinion4(1.4)2(0.9)1(1.9)1(0.0)3(2.0)0(0.0)Average burden1.21.31.11.21.31.2aMissing: 4 respondents.Figure 1.Stacked bar graph of user perspectives. Agreement scores were measured using a five-point Likert-type scale. The average agreement score per statement is indicated on the far right. The percentages represent the share of respondents. DBM: Dutch Biologic Monitor; ADRs: adverse drug reactions.Conclusion:This study provides valuable insights in the patient perspective on a PRO-based drug safety monitoring system for inflammatory rheumatic diseases and other IMIDs, and provides several useful starting points to further stimulate and improve PRO-based CEM systems. Altogether, it appears feasible to establish a PRO-based drug safety monitoring system that monitors IMID patients’ real-world experience with ADRs that has a low burden for the participants.Disclosure of Interests:Leanne Kosse: None declared, Gerda Weits: None declared, Harald Vonkeman Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Celltrion, Galapagos, Gilead, GSK, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi-Genzyme, all outside the submitted work., Sander Tas Grant/research support from: AbbVie, Arthrogen, AstraZeneca, BMS, Celgene, Galapagos, GSK, MSD, Pfizer, Roche, Sanofi-Genzyme, all outside the submitted work., Frank Hoentjen Speakers bureau: Abbvie, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk, all outside the submitted work, Consultant of: Celgene, Janssen-Cilag, all outside the submitted work, Grant/research support from: Dr Falk, Janssen-Cilag, Abbvie, Takeda, all outside the submitted work, Martijn van Doorn Grant/research support from: Leopharma, Novartis, Abbvie, BMS, Celgene, Lilly, MSD, Pfizer, Sanofi-Genzyme, Janssen Cilag, outside the submitted work., Phyllis Spuls Grant/research support from: Departmental independent research grant for TREAT NL registry from different companies, is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of e.g. psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital and, is Chief Investigator (CI) of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children and one of the main investigators of the SECURE-AD registry, all outside the submitted work., Geert D’Haens Consultant of: Abbvie, Ablynx, Active Biotech AB, Agomab Therapeutics, Allergan, Alphabiomics, Amakem, Amgen, AM Pharma, Applied Molecular Therapeutics, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol Meiers Squibb/Celgene, Boehringer Ingelheim, Celltrion, Cosmo, DSM Pharma, Echo Pharmaceuticals, Eli Lilly, Engene, Exeliom Biosciences, Ferring, DrFALK Pharma, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Gossamerbio, Pfizer, Immunic, Johnson and Johnson, Kintai Therapeutics, Lycera, Medimetrics, Takeda, Medtronic, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Photopill, ProciseDx, Prodigest, Prometheus laboratories/Nestle, Progenity, Protagonist, RedHill, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestec/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor, all outside the submitted work, Michael Nurmohamed Speakers bureau: AbbVie, Celgene, Celltrion, Eli Lilly, Janssen, Sanofi, all outside the submitted work, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Roche, Sanofi, all outside the submitted work, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Mundipharma, Novartis, Pfizer, Roche, Sanofi, all outside the submitted work, Eugène van Puijenbroek: None declared, Bart van den Bemt: None declared, Naomi Jessurun: None declared

Atopic dermatitis comorbidities extend well beyond the march to allergic conditions (food allergy, asthma, allergic rhinitis, allergic conjunctivitis, and eosinophilic esophagitis), suggesting both cutaneous and systemic immune activation. In reviewing atopic dermatitis comorbidities, Councilors of the International Eczema Council found a strong pattern of immune activation in peripheral blood and the propensity to both skin and systemic infections. Associations with cardiovascular, neuropsychiatric, and malignant diseases were increasingly reported, but confirmation of their link with atopic dermatitis requires longitudinal studies. Given the possibility of atopic dermatitis-related systemic immune activation, future investigations of new interventions should concurrently examine the impact on these comorbidities.

Background:Patient-reported outcomes (PROs) are increasingly used in studies and medical practice to obtain information on patients’ perspectives towards their treatment or disease. However, study outcomes are primarily directed at and shared with healthcare professionals, even though the results may also be relevant for patients.Objectives:The objective of this study was to obtain insight in which results patients with immune-mediated inflammatory diseases (IMIDs), including inflammatory rheumatic disease patients, prefer to receive after participating in the Dutch Biologic Monitor.Methods:The Dutch Biologic Monitor is a PRO-based prospective cohort event monitoring study focused on adverse drug reactions (ADRs) [1]. A survey was conducted among the participants of the Dutch Biologic Monitor who wanted to be informed about the results. Patients’ preferences were identified using twelve statements and rated with five-point Likert-type scales. Averages described the preference per statement. Preference for the results per IMID or altogether was assessed using Mann-Whitney U Test.Results:Respondents (N=591, response rate 67.6%) preferred results per IMID over aggregated results (p=Table 1.Respondent characteristics.CharacteristicsAllInflammatory rheumatic disease patients(n=591)(%)(n=453)(%)Female gender,n(%)353(59.7)286(63.1)Age, median (IQR), years59.0(51.0-67.0)60.0(51.0-67.5)BiologicsAdalimumab220(37.2)164(36.2)Etanercept196(33.2)189(41.7)Infliximab43(7.3)8(1.8)Tocilizumab21(3.6)17(3.8)Ustekinumab21(3.6)7(1.5)Other90(15.2)68(15.0)Combination therapyMethotrexate195(33.0)183(40.4)Corticosteroids65(11.0)51(11.3)Thiopurines41(6.9)10(2.2)No combination therapy231(39.1)157(34.7)Other123(20.8)106(23.4)Indications for biologic therapyRheumatoid arthritis277(46.9)277(61.1)Psoriatic arthritis111(18.8)111(24.5)Ankylosing spondylitis/axSpA83(14.0)83(18.3)Other159(26.9)17(3.8)IQR: interquartile range; axSpA: axial spondyloarthritis.Figure 1.The preferences of patients on the communication of the reported adverse drug reaction information resulting from the Dutch Biologic Monitor.Conclusion:Participants of the Dutch Biologic Monitor that use a biologic for their IMID prefer to receive ADR information tailored to their own biologic and IMID. Furthermore, they want to obtain insight in the course of ADRs. Therefore, we advocate to generate disease-specific information on ADRs for IMID patients.References:[1]Kosse LJ, Jessurun NT, Hebing RCF, Huiskes VJB, Spijkers KM, van den Bemt BJF, et al. Patients with inflammatory rheumatic diseases: quality of self-reported medical information in a prospective cohort event monitoring system.Rheumatol.published on 30 Sept 2019. doi: 10.1093/rheumatology/kez412.Disclosure of Interests:Gerda Weits: None declared, Leanne Kosse: None declared, Harald Vonkeman: None declared, Phyllis Spuls Grant/research support from: Departmental independent research grant for TREAT NL registry LeoPharma December 2019; Contract support: I am involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of e.g. psoriasis and atopic dermatitis for which we get financial compensation paid to the department/hospital, Consultant of: Consultancies in the past for Sanofi 111017 and AbbVie 041217 (unpaid), Bart van den Bemt Grant/research support from: UCB, Pfizer and Abbvie, Consultant of: Delivered consultancy work for UCB, Novartis and Pfizer, Speakers bureau: Pfizer, AbbVie, UCB, Biogen and Sandoz., Sander Tas: None declared, Frank Hoentjen Grant/research support from: Received grants from Dr Falk, Janssen-Cilag, and AbbVie., Consultant of: Served on advisory boards, or as speaker or consultant for AbbVie, Celgene, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz, and Dr Falk, Speakers bureau: Served on advisory boards, or as speaker or consultant for AbbVie, Celgene, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz, and Dr Falk, Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research, Martijn van Doorn Grant/research support from: Unrestricted grants, advisory board, speaker fees and/or other (investigator) from Novartis, Abbvie, Janssen Cilag, Leopharma and Pfizer, Speakers bureau: Unrestricted grants, advisory board, speaker fees and/or other (investigator) from Novartis, Abbvie, Janssen Cilag, Leopharma and Pfizer, Eugène van Puijenbroek: None declared, Naomi Jessurun: None declared

The development of core outcome sets (COS), i.e. a minimum set of 'core outcomes' that should be measured and reported in all trials or clinical practice of a specific condition, in dermatology is gathering pace. A total of 44 dermatology-related COS projects have been registered in the online Core Outcome Measures in Effectiveness Trials (COMET) database (http://www.comet-initiative.org/studies/search), and include studies on 26 different skin diseases. With the increasing number of COS in dermatology, care is needed to ensure the delivery of high quality COS that meet quality standards based on state of the art methodology. In 2015, the Cochrane Skin - Core Outcome Set Initiative (CS-COUSIN) was established. CS-COUSIN is an international, multidisciplinary working group, aiming to improve the development and implementation of COS in dermatology. CS-COUSIN has developed guidance on how to develop high quality COS for skin diseases, and supports dermatology-specific COS initiatives. Currently, 16 COS development groups are affiliated to CS-COUSIN following standardized COS development processes. To ensure successful uptake of COS in dermatology, researchers, clinicians, systematic reviewers, guideline developers and other stakeholders should use existing COS in their work.

Contains fulltext : 208399.pdf (Publisher’s version ) (Open Access) BACKGROUND: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. METHODS: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for >/=16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or >/=64 of ustekinumab treatment. RESULTS: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (

Evidence-based health care requires that relevant outcomes for patients are included in clinical trials investigating treatment effects, allowing subsequent systematic reviews to summarize all relevant evidence to guide clinical practice. Currently, no gold standard of outcome choice for dermatology trials and reviews exists. We systematically assessed concordance between efficacy outcomes in a random sample of 10 Cochrane Skin systematic reviews and the 220 dermatology trials included. Reviews did not include 742 (68%) of the 1,086 trial outcomes. Of the 60 outcomes the reviews sought, 17 (28%) were not reported in any trial, while 12 were assessed in

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of systemic immunosuppressive treatments for people with moderate-to-severe atopic eczema.