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(1) Background: Achieving inactive disease decreases long-term joint damage in patients with polyarticular juvenile idiopathic arthritis (polyJIA). The aim of our study was to describe average time to treatment and medication changes over time. (2) Methods: Incident polyJIA patients were retrospectively identified in the InGef and WIG2 longitudinal health claims databases. Drug escalation level changes were evaluated longitudinally and cross-sectionally across three years, as follows: no treatment, glucocorticoids (GCs) and/or non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biological disease-modifying antirheumatic drugs (bDMARDs). (3) Results: On average, newly diagnosed polyJIA patients received their first csDMARD prescription after 128 days and their first bDMARD prescription after 327 days. More patients were treated with csDMARDs than with bDMARDs at diagnosis; however, 24% and 12% (InGef and WIG2 databases, respectively) had no JIA treatment. After three years, 45% and 31% were not taking any treatments, while 18% and 36% were prescribed bDMARDs. Among patients initiating bDMARDs, most continued treatment for three years, with some switching to csDMARDs or discontinuing treatment. Patients treated only with csDMARDs took them longer, compared to those additionally taking other DMARDs. Patients treated with bDMARDs took them about twice as long as the csDMARDs they took prior. (4) Conclusion: A substantial number of patients with polyJIA are not treated as intensively as guidelines recommend.

Introduction: For chronic diseases such as axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PsO), treatment goals include remission or at least low disease activity (LDA) by 12 weeks. Improvements in symptoms such as pain and fatigue should also be treatment goals., Methods: ADEQUATE was a German, prospective, non-interventional study to evaluate the proportion of patients with rheumatoid arthritis, PsA, axSpA, or PsO who, in routine clinical practice, benefit from the continuation of treatment with etanercept (ETN) beyond 12 weeks, even when their treatment goals have not yet been reached. Patient-reported outcomes (PROs) and changes in concomitant glucocorticoid use were also recorded. This article focuses on results for patients with axSpA and PsA; data for patients with PsO are described briefly., Results: In total, 305, 254, and 70 patients with axSpA, PsA, and PsO, respectively, were included. Rates of remission at week 12 and week 24, respectively, were 19% and 18% for axSpA, 38% and 51% for PsA, and 7% and 19% for PsO. Rates of LDA at week 12 and week 24, respectively, were 39% and 45% for axSpA, 50% and 60% for PsA, and 34% and 51% for PsO. Extending treatment up to 52 weeks was associated with stable rates of or further increases in remission and LDA rates. Improvements in pain, fatigue, and depression (axSpA, PsA, and PsO) and reductions in concomitant glucocorticoid use (axSpA and PsA) were observed. No new safety signals were detected., Conclusion: These findings confirm the effectiveness and safety of ETN in routine clinical practice for several indications and highlight potential benefits of continuing ETN treatment in patients who have not reached their treatment goals after 12 weeks. Additional benefits included improvements in PROs and reduction of concomitant glucocorticoids., Trial Registration: ClinicalTrials.gov NCT02486302., (© 2024. The Author(s).)

Introduction: Etanercept (ETN) has been shown to slow radiographic progression of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical trials. This real-world, non-interventional study assessed radiographic progression in patients with RA or PsA treated with ETN for ≤ 36 months in outpatient care in Germany (NCT01623752)., Methods: Patients with RA or PsA attended ≤ 10 visits across two study phases (phase 1: seven visits, baseline to month 18; phase 2: three visits until month 36). Radiographs were taken at baseline (Rx1), months 12-18 (Rx2), and/or months 30-36 (Rx3). Historic radiographs (Rx0) taken 12-48 months pre-baseline were also evaluated (if available). The primary endpoint was the change in modified total Sharp score (mTSS). The erosion score (ES) and joint space narrowing score (JSN) were also evaluated., Results: Overall, 1821 patients were enrolled (RA: n = 1378; PsA: n = 440). In patients with Rx1 and Rx2 (RA: n = 511; PsA: n = 167), the mean mTSS remained stable for both disease groups, and the annualized median change in mTSS was 0. In patients with Rx0, Rx1, and Rx2 (RA: n = 180; PsA: n = 47), annualized radiographic progression in mTSS, ES, and JSN was larger in the pre-ETN treatment phase than during ETN treatment in both disease groups. The percentage of patients with radiographic non-progression was higher during ETN treatment versus pre-ETN. Improvement in clinical disease activity and patient-reported outcomes was also observed., Conclusions: This was the first real-world, non-interventional study to report systematically collected radiographic data in a large cohort of patients with RA or PsA under treatment with a biologic. In patients with available radiographic data, mean radiographic progression was lower and the proportion of patients without progression was greater during ETN treatment than in the pre-ETN period., (© 2022. The Author(s).)

Background: Juvenile idiopathic arthritis (JIA) describes heterogenous categories of chronic inflammatory rheumatic conditions of unknown origin in children and adolescents. Epidemiological data in the literature vary, depending on geographic location, ethnicity and the case definition used. We evaluated epidemiology, especially that of the categories defined by the International League of Associations for Rheumatology (ILAR)., Methods: Using data from two different longitudinal health claims databases (WIG2 and InGef) from January 1 st , 2013 to December 31 st , 2019, we looked at patients aged 2 to 15 years old with at least one main inpatient or two secondary inpatient/verified outpatient ICD-10 diagnoses in at least two different quarters within one calendar year. We calculated prevalence and incidence (per 100,000 patients) and extrapolated data to the entire German population, looking at differences in gender and age groups. Additionally, we collected data on "other" not necessary comorbidities in our JIA patient population., Results: Of the 3-4 million patients in the databases (respectively) in 2018, we found a total of 546 (WIG2) and 849 (InGef) patients that met our JIA case definition, with an incidence of 34 (29-41) and 60 (53-67) and prevalence of 133 (122-145) and 168 (157-179). Both incidence and prevalence throughout the age range were mostly higher in females than males, however the difference between females and males increased with increasing age. Of the ILAR categories, oligoarthritis was the most prevalent (70 and 91 per 100,000), with about half of our JIA patients in this category, followed by undifferentiated arthritis (49 and 56 cases per 100,000) and rheumatoid factor negative (RF-) (31 and 39 per 100,000). Incidence in 2018 was the highest in these three categories. Atopic dermatitis, vasomotor and allergic rhinitis, and uveitis were the pre-defined comorbidities seen most often in both databases., Conclusion: This study provides current incidence and prevalence JIA data in Germany, contributing to knowledge on burden of disease and tools for healthcare planning., (© 2022. The Author(s).)

Background: For rheumatoid arthritis (RA), the treat-to-target concept suggests attaining remission or at least low disease activity (LDA) after 12 weeks., Objectives: This German, prospective, multicenter, non-interventional study aimed to determine the proportion of patients with RA who achieved their treat-to-target aim after 12 and 24 weeks of etanercept (ETN) treatment in a real-life setting, as opposed to patients achieving their therapeutic target at a later timepoint (week 36 or 52)., Methods: A total of 824 adults with a confirmed diagnosis of RA without prior ETN treatment were included. Remission and LDA were defined as DAS28 < 2.6 and DAS28 ≤ 3.2, respectively., Results: The proportion of patients achieving remission was 24% at week 12 and 31% at week 24. The proportion of patients achieving LDA was 39% at week 12 and 45% at week 24. The proportion of patients achieving remission or LDA further increased beyond week 24 up to week 52. Improvement in pain and reduction in concomitant glucocorticoid treatment were observed. Improvements in patient-reported outcomes were also seen in patients who did not reach remission or LDA. No new safety signals were detected., Conclusions: A considerable proportion of patients with RA attained the target of remission or LDA after 12 weeks of ETN treatment. Even beyond that timepoint, the proportion of patients achieving treatment targets continued to increase up to week 52., Trial Registration: ClinicalTrials.gov Identifier: NCT02486302., (© 2022. The Author(s).)

Objectives: Hand osteoarthritis (OA) is a condition characterised by cartilage degradation and frequently erosive changes. Analgesics and non-steroidal anti-inflammatory drugs are used for symptomatic relief but are often poorly tolerated or contraindicated. Previous publications suggest hydroxychloroquine (HCQ) as a possible treatment for hand OA. The OA-TREAT study aimed to investigate the efficacy and safety of HCQ in patients with inflammatory and erosive hand OA (EOA)., Methods: OA-TREAT was an investigator-initiated, multicentre, randomised, double-blind, placebo (PBO)-controlled trial. Patients with inflammatory and EOA, according to the ACR criteria, with radiographically erosive disease were randomised 1:1 to HCQ 200-400 mg/day or PBO for 52 weeks (W52). Both groups received stable standard therapy. The primary endpoint was Australian Canadian Hand Osteoarthritis Index (AUSCAN) for pain and hand disability at W52., Results: 75 patients were randomised to HCQ and 78 to PBO. At W52, mean AUSCAN pain was 26.7 in HCQ and 26.5 in PBO patients (p=0.92). Hand disability measured by AUSCAN function (mean) was 48.1 in HCQ and 51.3 in PBO patients (p=0.36). Changes in radiographic scores did not differ significantly (p>0.05) between treatment groups. There were 7 serious adverse events in the HCQ and 15 in the PBO group., Conclusions: OA-TREAT is the first large randomised PBO controlled trial focusing on EOA. HCQ was no more effective than PBO for changes in pain, function and radiographic scores in the 52-week period. Overall safety findings were consistent with the known profile of HCQ., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Two complementary measurement systems-built upon an autonomous floating craft and a tethered balloon-for lake research and monitoring are presented. The autonomous vehicle was assembled on a catamaran for stability, and is capable of handling a variety of instrumentation for in situ and near-surface measurements. The catamaran hulls, each equipped with a small electric motor, support rigid decks for arranging equipment. An electric generator provides full autonomy for about 8 h. The modular power supply and instrumentation data management systems are housed in two boxes, which enable rapid setup. Due to legal restrictions in Switzerland (where the craft is routinely used), the platform must be observed from an accompanying boat while in operation. Nevertheless, the control system permits fully autonomous operation, with motion controlled by speed settings and waypoints, as well as obstacle detection. On-board instrumentation is connected to a central hub for data storage, with real-time monitoring of measurements from the accompanying boat. Measurements from the floating platform are complemented by mesoscale imaging from an instrument package attached to a He-filled balloon. The aerial package records thermal and RGB imagery, and transmits it in real-time to a ground station. The balloon can be tethered to the autonomous catamaran or to the accompanying boat. Missions can be modified according to imagery and/or catamaran measurements. Illustrative results showing the surface thermal variations of Lake Geneva demonstrate the versatility of the combined floating platform/balloon imagery system setup for limnological investigations., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To compare sleep quality, disease activity and patient-reported outcomes such as fatigue and immune parameters in patients with rheumatoid arthritis treated with etanercept (ETA) or methotrexate (MTX)., Methods: Of 36 patients (28-joint Disease Activity Score, DAS28CRP≥3.2) in this 16-week (w), open, prospective study, 19 (11 women) received MTX 12.5-17 mg/w, and 17 (14 women) received ETA 25 mg x 2/w, alone or in combination with MTX. Clinical (DAS28CRP, visual analogue scale), laboratory (C-reactive protein [CRP]), sleep (polysomnography), functional (Multidimensional Fatigue Inventory; Health Assessment Questionnaire-Disability Index (HAQ-DI); 36-item Short-Form Health Survey (SF-36), immunological (humoral/cellular) and neuroendocrine (hormonal) parameters were recorded at baseline (BL), w8 and w16., Results: BL characteristics did not differ significantly between the ETA and MTX groups except disease duration: mean age (years): 48.6±8.8 vs. 49.4±16.6; mean disease duration (months): 19.6±46.3 vs. 81.2±79.2; and DAS28CRP: 4.4±0.9 vs. 4.4±1.7, respectively. DAS28CRP, SF-36, and HAQ-DI improved significantly in both groups from BL to w16 (p≤0.05). The DAS28CRP improvements at w16 (mean changes -1.8 in the ETA group, and -1.4 in MTX group), were not statistically significant from each other. The absolute values of sleep efficiency, total sleep time, and stage 2 sleep duration increased significantly in the ETA group, but no significant changes were reported in the MTX group., Conclusions: Both therapies improved disease activity, CRP, SF-36 and HAQ-DI, with faster, more pronounced changes in DAS28CRP in the ETA group, which alone had significantly improved sleep parameters.

Objectives: Vitamin D (VitD) deficiency is a health problem prevalent not only in the elderly but also in young adults. The primary objective of our observational pilot study "MUVY" (Mood, UVR, Vitamin D in Young women) was to test both the short-term and long-term effects of a series of three suberythemal UV radiation (UVR) exposures on the VitD status and well-being of young healthy women during winter in a repeat measure design., Methods: 20 healthy young women (Fitzpatrick skin types I-III, aged 21-25 years) received three full body broad band UVR exposures with an escalating erythemally weighted dose schedule during one week in winter, and completed self-report questionnaires monitoring symptoms of depression (Beck Depression Inventory, BDI) and affective state/well-being (Profile of Mood States, POMS) at baseline and three days after the last UVR exposure. 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in serum at baseline, and at study days 8, 36 and 50., Results: Mean baseline 25(OH)D level was 54.3 nmol/L (standard deviation (s.d.) = 24.1), with seven women having VitD deficient status. Relevant symptoms of depression, as indicated by low BDI total scores (0-8), were absent. After the three UVR exposures the increment of 25(OH)D was an average of 13.9 nmol/L (95% confidence interval (CI) = 9.4-18.4) and 26.2 pmol/L (95%CI = 7.2-45.1) for 1,25(OH)2D. Δ25(OH)D, and corresponding baseline levels were significantly and inversely associated (rho = -0.493, p = 0.027). Only 25(OH)D remained significantly increased above baseline for at least six weeks after the last UVR exposure. A strong inverse correlation of the POMS subscale "Vigor/Activity" and the increment in 1,25(OH)2D was found (rho = -0.739, p<0.001) at day 8., Conclusions: Three suberythemal whole body UVR exposures during one week are a simple and suitable method for improving 25(OH)D levels during winter, for at least six weeks, and especially in young women with VitD deficient status., Trial Registration: German Clinical Trials Register (Deutsches Register Kinischer Studien) DRKS00009274., Competing Interests: The authors have declared that no competing interests exist.

Anti-thymocyte globulin (ATG) is used in the treatment of acute organ rejection. We studied in vitro the effect of low-dose ATG on B-cell activation and differentiation to antibody-secreting cells, as this may have an effect on B cell-driven autoimmune diseases, such as pemphigus vulgaris. Immunoglobulin production was analysed in the supernatants of peripheral blood mononuclear cells (PBMC) and CD19+ B cells from healthy donors and from patients with different autoimmune diseases. B-cell proliferation, viability and differentiation were analysed using flow cytometry. Differentiation of B cells to immunoglobulin G (IgG) secreting cells was significantly reduced by ATG, but not by control unspecific IgG from non-immunized rabbits (rIgG). B-cell viability was not altered by sub-depleting concentrations of ATG. In contrast, B-cell proliferation was enhanced by ATG. When PBMC from patients with autoimmune diseases were studied, specific autoantibodies could be detected in 1 out of 10 patients. In this patient, who had pemphigus vulgaris, ATG not only decreased total IgG, but decreased also specific anti-desmoglein-3. In conclusion, these data suggest that ATG at low concentrations inhibits B-cell differentiation and function.

Biologics, possibly in combination with a conventional disease-modifying antirheumatic drug (DMARD) - preferably methotrexate (MTX), are used in accordance with the recommendations of the international rheumatological societies. However, in clinical practice, this recommendation is often problematic, as many rheumatologists know from personal experience. The quality of life of the patient is affected mainly by drug-induced intolerances (eg, MTX). Thus, the acceptance of the patient to treatment is often so inadequate that a discontinuation of the drug is necessary. In daily practice, approximately 30% of patients with biological therapy receive no concomitant DMARD according to the register data.

Background: Osteoarthritis (OA) is a heterogeneous group of conditions with disturbed integrity of articular cartilage and changes in the underlying bone. The pathogenesis of OA is multifactorial and not just a disease of older people. Hydroxychloroquine (HCQ) is a disease-modifying anti-rheumatic drug (DMARD) typically used for the treatment of various rheumatic and dermatologic diseases. Three studies of HCQ in OA, including one abstract and one letter, are available and use a wide variety of outcome measures in small patient populations. Despite initial evidence for good efficacy of HCQ, there has been no randomized, double-blind, and placebo-controlled trial in a larger patient group. In the European League Against Rheumatism (EULAR), evidence-based recommendations for the management of hand OA, HCQ was not included as a therapeutic option because of the current lack of randomized clinical trials., Methods/design: OA TREAT is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial. A total of 510 subjects with inflammatory and erosive hand OA, according to the classification criteria of the American College of Rheumatology (ACR), with recent X-ray will be recruited across outpatient sites, hospitals and universities in Germany. Patients are randomized 1:1 to active treatment (HCQ 200 to 400 mg per day) or placebo for 52 weeks. Both groups receive standard therapy (non-steroidal anti-inflammatory drugs [NSAID], coxibs) for OA treatment, taken steadily two weeks before enrollment and continued further afterwards. If disease activity increases, the dose of NSAID/coxibs can be increased according to the drug recommendation. The co-primary clinical endpoints are the changes in Australian-Canadian OA Index (AUSCAN, German version) dimensions for pain and hand disability at week 52. The co-primary radiographic endpoint is the radiographic progression from baseline to week 52. A multiple endpoint test and analysis of covariance will be used to compare changes between groups. All analyses will be conducted on an intention-to-treat basis., Discussion: The OA TREAT trial will examine the clinical and radiological efficacy and safety of HCQ as a treatment option for inflammatory and erosive OA over 12 months. OA TREAT focuses on erosive hand OA in contrast to other current studies on symptomatic hand OA, for example, HERO [Trials 14:64, 2013]., Trial Registration: ISRCTN46445413, date of registration: 05-10-2011.