Johannes Knitza

BACKGROUND: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission. METHODS: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded. RESULTS: The median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell-associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization. CONCLUSIONS: In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.).

BACKGROUND: Mobile health apps (MHA) have the potential to improve health care. The commercial MHA market is rapidly growing, but the content and quality of available MHA are unknown. Instruments for the assessment of the quality and content of MHA are highly needed. The Mobile Application Rating Scale (MARS) is one of the most widely used tools to evaluate the quality of MHA. Only few validation studies investigated its metric quality. No study has evaluated the construct validity and concurrent validity. OBJECTIVE: This study evaluates the construct validity, concurrent validity, reliability, and objectivity, of the MARS. METHODS: Data was pooled from 15 international app quality reviews to evaluate the metric properties of the MARS. The MARS measures app quality across four dimensions: engagement, functionality, aesthetics and information quality. Construct validity was evaluated by assessing related competing confirmatory models by confirmatory factor analysis (CFA). Non-centrality (RMSEA), incremental (CFI, TLI) and residual (SRMR) fit indices were used to evaluate the goodness of fit. As a measure of concurrent validity, the correlations to another quality assessment tool (ENLIGHT) were investigated. Reliability was determined using Omega. Objectivity was assessed by intra-class correlation. RESULTS: In total, MARS ratings from 1,299 MHA covering 15 different health domains were included. Confirmatory factor analysis confirmed a bifactor model with a general factor and a factor for each dimension (RMSEA = 0.074, TLI = 0.922, CFI = 0.940, SRMR = 0.059). Reliability was good to excellent (Omega 0.79 to 0.93). Objectivity was high (ICC = 0.82). MARS correlated with ENLIGHT (ps<.05). CONCLUSION: The metric evaluation of the MARS demonstrated its suitability for the quality assessment. As such, the MARS could be used to make the quality of MHA transparent to health care stakeholders and patients. Future studies could extend the present findings by investigating the re-test reliability and predictive validity of the MARS.

BACKGROUND: Mobile health (mHealth) defines the support and practice of health care using mobile devices and promises to improve the current treatment situation of patients with chronic diseases. Little is known about mHealth usage and digital preferences of patients with chronic rheumatic diseases. OBJECTIVE: The aim of the study was to explore mHealth usage, preferences, barriers, and eHealth literacy reported by German patients with rheumatic diseases. METHODS: Between December 2018 and January 2019, patients (recruited consecutively) with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were asked to complete a paper-based survey. The survey included questions on sociodemographics, health characteristics, mHealth usage, eHealth literacy using eHealth Literacy Scale (eHEALS), and communication and information preferences. RESULTS: Of the patients (N=193) who completed the survey, 176 patients (91.2%) regularly used a smartphone, and 89 patients (46.1%) regularly used social media. Patients (132/193, 68.4%) believed that using medical apps could be beneficial for their own health. Out of 193 patients, only 8 (4.1%) were currently using medical apps, and only 22 patients (11.4%) stated that they knew useful rheumatology websites/mobile apps. Nearly all patients (188/193, 97.4%) would agree to share their mobile app data for research purposes. Out of 193 patients, 129 (66.8%) would regularly enter data using an app, and 146 patients (75.6%) would welcome official mobile app recommendations from the national rheumatology society. The preferred duration for data entry was not more than 15 minutes (110/193, 57.0%), and the preferred frequency was weekly (59/193, 30.6%). Medication information was the most desired app feature (150/193, 77.7%). Internet was the most frequently utilized source of information (144/193, 74.6%). The mean eHealth literacy was low (26.3/40) and was positively correlated with younger age, app use, belief in benefit of using medical apps, and current internet use to obtain health information. CONCLUSIONS: Patients with rheumatic diseases are very eager to use mHealth technologies to better understand their chronic diseases. This open-mindedness is counterbalanced by low mHealth usage and competency. Personalized mHealth solutions and clear implementation recommendations are needed to realize the full potential of mHealth in rheumatology.

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.