A long-term follow-up study of the Hand Eczema Trial (HET): a randomized clinical trial of a secondary preventive programme introduced to Danish healthcare workers.

BACKGROUND: Preventive skin care programmes have shown beneficial effects on the prevalence and severity of hand eczema, but most trials only report short-term outcomes. One such trial was the randomized Hand Eczema Trial (HET, 2009) investigating the effects of a secondary prevention programme in healthcare workers. Positive results have been reported at 5-month follow-up. OBJECTIVES: To examine the long-term (42-47 months) effects of the HET. METHODS: The present study was a follow-up questionnaire study on the effect of the intervention. Outcomes were the presence and severity of hand eczema, health-related quality of life (HR-QoL), skin protective behaviour, and knowledge of skin protection. A supplementary outcome was general improvement/worsening of hand eczema. RESULTS: Comparison of the outcomes at follow-up showed no marked differences between the two groups. General improvement was reported by 70% in the intervention group and by 54% in the control group (p = 0.25). A small, statistically significant improvement was found regarding HR-QoL in the intervention group only (p = 0.015). CONCLUSIONS: The impact of an intervention that is effective after 5 months is attenuated over time, with no long-term effect on the outcomes examined. We suggest that skin care education should be repeated at regular intervals.

Challenges of designing and conducting cohort studies and clinical trials in populations of pregnant people.

Rheumatic and musculoskeletal diseases often affect individuals of childbearing age. The incidence and prevalence of rheumatic and musculoskeletal diseases is rising. More pregnancies in patients with rheumatic and musculoskeletal diseases are anticipated and some rheumatic and musculoskeletal diseases are associated with pregnancy complications (eg, miscarriages, fetal deaths, preterm births, and hypertensive disorders in pregnancy). Despite the need to understand the use of drugs to treat rheumatic and musculoskeletal diseases in pregnancy, clinical trials in pregnancy are rare, therapeutics in pregnancy are understudied, and pregnant individuals are routinely excluded as premarketing trial participants. Data on the effectiveness and safety of disease-modifying antirheumatic drugs are most often based on post-marketing observational data. Observational studies assessing the bidirectional relationship between rheumatic and musculoskeletal diseases and pregnancy, as well as interventional studies of treatments during pregnancy, are scarce. Historical reluctance to perform studies in what was deemed an at-risk group persists in pharmaceutical companies, regulatory bodies, and ethics boards. Additionally, patients must be engaged partners, which requires trust that the research respects the needs and interests of the patient and complies with the rules intended to protect the pregnant person and the fetus from harm. In this Series paper, we share challenges we have encountered in conducting prospective cohort studies and interventional trials of postmarketing approved medications, assessing pregnancy specific outcomes in pregnant women with rheumatic and musculoskeletal diseases in the EU, the UK, and the USA. We discuss the changing landscape around trials in pregnancy and present possible solutions to our challenges.

Reduced Humoral Response of SARS-CoV-2 Antibodies following Vaccination in Patients with Inflammatory Rheumatic Diseases-An Interim Report from a Danish Prospective Cohort Study.

Background/Purpose: In light of the current COVID-19 pandemic, whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease-modifying drugs (DMARDs) exhibit an adequate immune response to the currently available SARS-CoV-2 vaccinations remains a major concern. There is an urgent need for more SARS-CoV-2 vaccine efficacy data to inform healthcare providers on the potential need for a booster vaccine. We established the 'Detection of SARS-CoV-2 antibodies in Danish Inflammatory Rheumatic Outpatients' study (DECODIR) in March 2021 in order to assess and compare the immunoglobulin G (IgG response) of the SARS-CoV-2 BNT162b2 vaccine (Pfizer, Groton, CT, USA/BioNTech, Mainz, Germany) and mRNA-1273 vaccine (Moderna, Cambridge, MA, USA) administered as part of the national vaccine roll out in patients with RMDs, irrespective of treatment. Patients' SARS-CoV-2 IgG level was used as proxy to determine vaccination response. Methods: The study is a longitudinal prospective cohort study in which the SARS-CoV-2 antibody response was measured and compared at baseline and at six weeks following vaccination. The study population consisted of patients with rheumatoid arthritis (RA), spondyloarthropathies (SpA), or psoriatic arthritis (PsA) receiving their outpatient treatment at the Danish Hospital for Rheumatic Diseases, Sonderborg. Bloods, patient reported outcome measurements (PROMS), clinical data, and treatment information (cs/bDMARD) were collected at baseline/6 weeks and documented in the Danish DANBIO registry. Commercially available antibody tests (ThermoFisher, Waltham, MA, USA) were used, and SARS-CoV-2 IgG levels were reported in EliA U/mL. Sufficient IgG response was defined as ≥10 EliA U/mL (manufacturers cut-off). Associations between antibody response, age, gender, disease (RA/PsA/SpA), no treatment or cs/bDMARD treatment, and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR), and bootstrapped 95% confidence interval (CI) of the median. Results: A total of 243 patients were included. We observed a significant increase in IgG levels (median of <0.7 EliA U/mL at baseline versus 34.5 EliA U/mL at 6 weeks). Seventy-two patients (32%) had an insufficient IgG response. The median IgG level in patients treated with cs/bDMARD combination therapy was significantly lower compared to patients without any DMARD treatment (12 EliA U/mL vs. 92 EilA U/mL (p < 0.01)). Conclusion: Patients treated with a combination of cs/bDMARD are at significantly higher risk of an inadequate response to SARS-CoV-2 vaccines as measured by IgG level compared to patients without DMARD treatment. IgG SARS-CoV-2 are only part of the immune response, and further data are urgently needed. At present, our results may inform healthcare providers and policy makers on the decision for the need of a booster vaccine in this particular patient group.

Validation of a Screening Questionnaire for Chronic Leg Ulcers.

The use of a validated screening questionnaire to identify individuals with chronic leg ulcers allows large-scale population-based studies to be conducted that measure and monitor the prevalence of the disease. The aim of this study was to design and validate such a screening questionnaire to identify patients with chronic leg ulcers. A simple 3-item questionnaire was developed at the Department of Dermatology, University Hospital of Zealand, Denmark. In total, 90 patients attending the department's outpatient clinic for dermatological diseases and chronic wounds were included in this study. All included participants completed the questionnaire and were subsequently examined by dermatologists. We found that the constructed 3-item questionnaire in this study had a sensitivity and specificity of 95% and 93% and a positive predictive value and negative predictive value of 78% and 95%, respectively. Moreover, we found that the use of the 3-item questionnaire, as compared with a single question, in which the participants were asked whether they currently have a leg ulcer, resulted in significantly higher positive predictive value (+11.6%, P = .035) and specificity (+5.6%, P = .046) of the diagnostic test. Future studies are merited to investigate the diagnostic accuracy of the questionnaire in other populations and settings.