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 1.71-14.78]), 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.

Associations between health literacy and patient outcomes in adolescents and young adults with cystic fibrosis.

BACKGROUND: Interactive health literacy (HL) skills enable individuals to participate more fully in healthcare activities and play a role in improving their outcomes. We examine the associations between HL and cystic fibrosis (CF) outcomes and compare HL in a sample from both the Irish CF and general populations. METHODS: A total of251 CF Registry participants aged 13-30 years completed the HLS-EU-Q16 survey and a disease-specific instrument for measuring quality of life (QoL) in CF. Health outcome and healthcare resource utilization (HCRU) data were sourced from the registry. CF patient outcomes were examined using generalized linear models (GLMs) with interactive HL categorization included as a factor. General population interactive HL data are from the 2011 European HL Survey (HLS-EU). Interactive HL in 180 age-sex matched CF and general population individuals was examined using a GLM with study population, sex and educational level included as factors and age as a covariate. RESULTS: Sufficient interactive HL (total sum score ≥13) was self-reported by 81.7% of individuals with CF. Sufficient HL was associated with fewer outpatient visits [7.02(SD = 6.7: 7.4) vs. 8.74(SD = 7.9: 9.6), P < 0.001], days hospitalized [10.25(SD = 9.8: 10.7) vs. 12.8(SD = 11.8: 13.9), P < 0.001], days on intravenous antibiotics [15.3(SD = 14.7: 15.8) vs. 19.7(18.5: 21.1), P < 0.001], days on oral antibiotics [27.4(SD = 26.7: 28.1) vs. 48.48(38.7: 42.4), P < 0.001] and better QoL [77.1(SD = 75.4-78.9) vs. 64.6(60.8-68.3), P < 0.001]. Mean HL scores in CF and general populations were sufficient, although higher among individuals with CF (14.3 vs. 13.1, P < 0.01). CONCLUSION: CF adolescents and young adults with sufficient levels of HL to obtain, understand, appraise and apply health information have better health-related outcomes.

Validation and use of a parametric model for projecting cystic fibrosis survivorship beyond observed data: a birth cohort analysis.

BACKGROUND: The current lifetable approach to survival estimation is favoured by CF registries. Recognising the limitation of this approach, we examined the utility of a parametric survival model to project birth cohort survival estimates beyond the follow-up period, where short duration of follow-up meant median survival estimates were indeterminable. METHODS: Parametric models were fitted to observed survivorship data from the US CF Foundation (CFF) Patient Registry 1980-1994 birth cohort. Model-predicted median survival was estimated. The best fitting model was applied to a Cystic Fibrosis Registry of Ireland dataset to allow an evaluation of the model's ability to estimate predicted median survival. This involved a comparison of birth cohort lifetable predicted and observed (Kaplan-Meier) median survival estimates. RESULTS: A Weibull model with main effects of gender and birth cohort was developed using a US CFF dataset (n=13,115) for which median survival was not directly estimable. Birth cohort lifetable predicted median survival for male and female patients born between 1985 and 1994 and surviving their first birthday was 50.9 and 42.4 years respectively. To evaluate the accuracy of a Weibull model in predicting median survival, a model was developed for the 1980-1984 Cystic Fibrosis Registry of Ireland birth cohort (n=243), which had an observed (Kaplan-Meier) median survival of 27.7 years. Model-predicted median survival estimates were calculated using data censored at different follow-up periods. The estimates converged to the true value as length of follow-up increased. CONCLUSIONS: Accurate prognostic information that is clinically critical for care of patients affected by rare, life-limiting disorders can be provided by parametric survival models. Problems associated with short duration of follow-up for recent birth cohorts can be overcome using this approach, providing better opportunities to monitor survival and plan services locally.

Shedding light on therapeutics in alopecia and their relevance to COVID-19.

As of July 9, 2020, there were more than 12 million confirmed cases of coronavirus disease 2019 (COVID-19) across the globe, with more than 550,000 deaths. Many European countries, including Belgium, the United Kingdom, Italy, and Spain, have had the highest numbers of fatalities per capita. This indicates the potential for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to overwhelm even the most advanced health care systems despite extreme societal interventions. Since its emergence, SARS-CoV-2 has disseminated across the globe, affecting the structure of global societies, infrastructure, and economies. Patients with alopecia are a diverse group who, for various indications, are prescribed a number of antimicrobials and antiandrogen treatments in addition to immunomodulatory therapies such as hydroxychloroquine, oral corticosteroids, and a range of broad immunosuppressants. These drugs are being scrutinized for their capacity to potentially affect SARS-CoV-2 outcomes. We examine these treatments and highlight the critical role that patient registries will play in generating real-world evidence to assess their impact on COVID-19 outcomes.

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.

Longitudinal Trends in Real-World Outcomes after Initiation of Ivacaftor. A Cohort Study from the Cystic Fibrosis Registry of Ireland.

RATIONALE: Patient registries have the potential to collect and analyze high-quality postauthorization data on new medicines. OBJECTIVES: We used cystic fibrosis (CF) registry data to assess outcomes after the initiation of ivacaftor, a CF transmembrane conductance regulator (CFTR) potentiator approved for the treatment of CF with a defective gating CFTR mutation. METHODS: Longitudinal trends were examined using mixed-effects regression analysis in 80 ivacaftor-treated patients with CF aged 6 to 56 years registered with the CF Registry of Ireland with at least 36 months of before and after commencement data. The effects of ivacaftor treatment on forced expiratory volume in 1 second (FEV1) % predicted, body mass index (BMI), hospitalization for pulmonary exacerbation, and oral and intravenous antibiotic use were assessed. RESULTS: In the 36 months after ivacaftor initiation, FEV1% predicted improved by 2.26% per annum (95% confidence interval [CI], 0.2 to 4.3) for patients aged younger than 12 years, remained unchanged for 12- to younger than 18-year-olds (95% CI, -1.9 to 2.9), and declined in adults by 1.74% per annum (95% CI, -3.1 to -0.4). BMI in adults increased 0.28 kg/m2 per annum (95% CI, 0.03 to 0.5), and there was no significant change in BMI z-score in children (95% CI, -0.01 to 0.1). In the year after ivacaftor initiation, intravenous antibiotic treatment reduced by 46% (95% CI, -62.5% to -23.3%, oral antibiotic treatment reduced by 49% (95% CI, -61.1% to -32.1%), and there was no significant reduction in hospitalization (95% CI, -59.2% to 9.7%). CONCLUSIONS: In this study of real-world CF registry data, clinical outcomes improved and healthcare resource utilization decreased after commencing ivacaftor.

Estimating Direct Cost of Cystic Fibrosis Care Using Irish Registry Healthcare Resource Utilisation Data, 2008-2012.

BACKGROUND: Understanding the determinants of cost of cystic fibrosis (CF) care and health outcomes may be useful for financial planning for the delivery of CF services. Registries contain information otherwise unavailable to healthcare activity/cost monitoring systems. We estimated the direct medical cost of CF care using registry data and examined how cost was affected by patient characteristics and CF gene (CF Transmembrane Conductance Regulator [CFTR]) mutation. METHODS: Healthcare resource utilisation data (2008-2012) were obtained for CF patients enrolled with the Irish CF Registry by 2013 from linked registry and national hospitalisation database records. Mean annual hospitalisation and medication per-patient costs were estimated by demographic profile, CFTR mutation, clinical status, and CF co-morbidity, and were presented in 2014 euro values. A mixed-effects regression model was used to examine the effect of demographic, CFTR mutation, and clinical outcomes on the log10 cost of direct medical CF care. RESULTS: Using 4261 observations from 1100 patients, we found that the median annual total cost per patient increased over the period 2008-2012 from €12,659 to €16,852, inpatient bed-day cost increased from €14,026 to €17,332, and medication cost increased from €5863 to €12,467. Homozygous F508-CFTR mutation (class II) cost was highest and milder mutation (class IV/V) cost was 49% lower. Baseline estimated cost in 2008 for a hypothetical underweight, homozygous F508del-CFTR 6-year-old female without chronic Pseudomonas aeruginosa/Staphylococcus aureus, CF-related diabetes (CFRD) or methicillin-resistant S. aureus (MRSA), and with a poor percent predicted forced expiratory volume in 1 s (ppFEV1) was €10,113, and was €21,082 in a 25-year-old with the same hypothetical profile. Chronic P. aeruginosa infection increased baseline cost by 39%, CF co-morbidity diabetes by 18%, and frequency of pulmonary exacerbation by 15%. Underweight, declining ppFEV1, chronic S. aureus colonisation, and time also influenced cost. CONCLUSIONS: CFTR mutation is an important factor influencing the cost of CF care. Costs differ among cohorts of CF patients eligible to access new and emerging CFTR repair therapies. These findings support the evaluation of outcome-associated cost in CFTR mutation-specific CF patient groups.