Torque Teno Virus quantification for monitoring of immunomodulation with biologic compounds in the treatment of rheumatoid arthritis.

OBJECTIVES: RA patients who fail to respond to MTX can receive biologic dMARDs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and its association with clinical response to bDMARDs. METHODS: The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-Ig (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood. RESULTS: TTV was measured in 95 patients (INF, n = 23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5 × 104 copies/ml [c/ml; interquartile range (IQR) 0-7.5 × 105] after 3 months. TTV levels at month 3 were associated with the Simplified Disease Activity Index (SDAI) (P = 0.03) and the Clinical Disease Activity Index (CDAI) response (P = 0.026) at month 6. A TTV cut-off level of 1.2 × 106 c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of an 85% reduction in SDAI at month 6. CONCLUSION: Our data suggest that TTV levels increase upon TNF, CD20 and costimulation blockade and are associated with the clinical response to bDMARDs in RA patients. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715.

Information technology concerning SDAI and CDAI.

Disease activity assessment of rheumatoid arthritis has never been trivial. Composite indices like the Disease Activity Score using 28 joint counts 28 (DAS28) and the Clinical Disease Activity Index (CDAI) and the Simplified Disease Activity Index (SDAI) attempted to integrate several core set variables into one readout, which eventually laid the grounds for implementation strategies that targeted disease activity levels, like remission. While CDAI and SDAI were clearly simpler at times when a calculator was needed, this has likely become less relevant in the era of digital records, where core set variables are entered into a computed device after measurement. However, DAS28 has faced new challenges, which are derived from its lack of specificity when it comes to assessing remission. Digital technology has advanced the management of patients with RA in clinical practice, since the disease activity levels can now be followed for each patient over adjustable time periods interesting for the clinician, such as since start of the last treatment. Also for research purposes, the digital records have allowed a more rapid course of projects from the scientific hypothesis to publication, simply by allowing to go to the digital database and select the items and observation needed. This has made clinical research much more efficient. In the digital era, the CDAI and SDAI can still be used on a piece of paper without the necessity of any electronic device, and it is exactly this flexibility and versatility of these two scores that account for their continued success.

Characteristics and outcome of critically ill patients with systemic rheumatic diseases referred to the intensive care unit.

OBJECTIVES: Patients with systemic rheumatic diseases (SRDs) are at risk of admission to the intensive care unit (ICU). Data concerning these critically ill patients are limited to few retrospective studies. METHODS: This is a single-centre retrospective study of patients with SRDs admitted to an ICU at the Vienna General Hospital between 2012 and 2020. Single-predictor and multiple logistic regression analysis was performed to identify potential outcome determinants. RESULTS: A total of 144 patients accounting for 192 ICU admissions were included. Connective tissue diseases (CTDs), vasculitides and rheumatoid arthritis were the most common SRDs requiring ICU admission. Leading causes for ICU admission were respiratory failure and shock, as reflected by a high number of patients requiring mechanical ventilation (60.4%) and vasopressor therapy (72.9%). Overall, 29.2% of admissions were due to SRD-related critical illness. In 70.8% patients, co-existent SRD not responsible for the acute critical illness was documented. When comparing these subgroups, CTDs and vasculitides had a higher frequency in the patients with SRD-related critical illness. In a significantly higher proportion of patients in the SRD-related subgroup, diagnosis of SRD was made at the ICU. ICU and 6-month mortality in the overall population was 20.3% and 38.5%, respectively. Age, glucocorticoid therapy prior to hospital admission and disease severity were associated with poor outcome. CONCLUSIONS: In this study, respiratory failure was the leading cause of ICU admission as reflected by high rates of required mechanical ventilation. Despite considerable severity of critical illness, survival rates were comparable to a general ICU population.

Loss of T cells expressing CD27 at the site of active tuberculosis - A prospective diagnostic study.

The lack of a rapid and reliable diagnostic test for active tuberculosis is still a burden to the control of the infection. The accumulation of Mycobacterium tuberculosis (MTB)-specific CD4+ T cells at the site of infection and the increase of MTB-specific CD27- cells seem to be characteristic for active tuberculosis. We evaluated CD27 expression of non-stimulated T cells at the site of infection compared to peripheral blood of seventy-two patients (n = 72) presenting with symptoms of active MTB-infection. Twenty patients (n = 20, 27.8%) were actually confirmed to have active tuberculosis. Overall, a significant increase of terminally differentiated CD27- CD4+ T cells at the site of disease was noted when compared to peripheral blood (<0.001). However, the loss of CD27 at the site of disease was not restricted to active tuberculosis (p = 0.253). The CD27 expression profile of tuberculosis patients was only discriminative to patients with malignancy.

Hand X-ray examination in two planes is not required for radiographic assessment of hand osteoarthritis.

AIMS: Radiographic imaging is essential in the diagnosis of hand osteoarthritis (HOA); however, it is unknown whether a multiplanar examination would add essential information to dorso-palmar (dp) views alone. This study evaluated whether an additional radiographic view would aid clinicians in the diagnostic process of HOA. METHODS: The dp radiographs of both hands from 159 HOA patients were assessed according to the scores described by Kellgren and Lawrence (K/L). In oblique view images, structures similar to classic ostophytes (OPs) were found, namely bony proliferations on the dorsal and/or ventral margins of joints, and were documented as dorsal/ventral OPs (dvOPs). Function and pain were assessed by applying standardised read-out systems. Logistic regression analysis and Mann-Whitney tests were implemented. RESULTS: The presence of dvOPs was associated with the degree of joint damage; however, dp views were sufficient to estimate radiographic changes. Only a few joints showed dvOPs as the only structural alteration; nevertheless, in almost all cases, classical radiographic OA changes were found in dp views of other joints of the same or the contralateral hand. The presence of dvOPs did not affect joint function or pain according to established scores, but was associated with radiographic progression in distal interphalangeal joints. CONCLUSION: This is the first study to confirm that additional radiographic planes, oblique/lateral views, are not necessary in the diagnostic process in HOA in daily clinical practice. Nevertheless, the presence of dvOPs reflect more severe joint damage and is associated with radiographic progression in HOA; hence, oblique/lateral views could be a useful tool for academic purposes.

Effects of a brief workplace-centered consultation for employees with musculoskeletal pain on health outcomes: a prospective cohort study.

Musculoskeletal (MSK) diseases affect a substantial proportion of the population. Specialist consultations were offered at the workplace for people with musculoskeletal (MSK)-complaints. We analyzed data on pain and well-being as well as health economic data at baseline. Lasting effects of the consultation were analyzed at a follow-up-interview after 12 months. Baseline data of 344 individuals were available. Occupations were divided into physically highly demanding (HD) or less demanding. Women reported significantly higher pain levels and less QoL than men. Sick leave days were significantly more in HD-workers. Independent of workload, significantly higher percentages of women had cervical- and upper limb-pain than men, with significantly higher pain in upper limbs in HD-workers. 235 participants were available for telephone-follow-up. QoL and MSK-pain improved significantly. Yearly out-of-pocket spendings for treatments significantly increased. NSAID use significantly decreased, whereas use of non-drug musculoskeletal-medical-services was significantly higher after one year. Regarding MSK-symptoms in gainfully employed individuals, the study showed significantly different workload-dependent differences in QoL. Significant effects of a consultation by a MSK-specialist were shown in terms of improved MSK-pain and overall well-being. This workplace-centered consultation had significant effects on beneficial health-behavior such as decreased use of NSAID and increased engagement in gymnastics and physiotherapy.

Risk profiling for a refractory course of rheumatoid arthritis.

BACKGROUND: Despite modern therapeutics and treatment strategies, a subset of rheumatoid arthritis (RA) patients remains insufficiently responsive to multiple therapies. Here, we identify predictors of such refractory RA ("reRA"). METHODS: Patients from a longitudinal academic clinical database with reRA (defined as failing to reach the treatment target of at least low disease activity with ≥3 DMARD courses, including ≥1 biological, over a total of ≥18 months) were compared to patients who did respond within the first two treatments (treatment amenable RA, "taRA"). We performed logistic regression analysis to identify risk factors for refractory disease, and several sensitivity analyses concerning different potential definitions for reRA to confirm the robustness of the results; key findings were also validated in an independent community cohort. RESULTS: We enrolled 412 patients, of whom 70 were reRA and 102 taRA; 240 patients fulfilled neither definition. ReRA patients were more frequently female (92.9 vs. 70.6%, p < 0.001), younger (44.37 vs. 51.14 years, p = 0.002), and had higher CDAI levels at first presentation (26.06 vs. 15.39, p < 0.001). Treatment delay was significantly longer for reRA than for taRA (3.17 vs. 1.45 years, p = 0.001). In multivariable analyses, treatment delay, female gender and higher disease activity remained as independent predictors of refractory disease. Based on the identified predictors, we developed a matrix model for risk of future reRA. CONCLUSIONS: Our data identified delay to initial treatment, female gender and higher disease activity as important predictors of a later refractory course of RA. Delay of treatment initiation is the single most important modifiable risk factor of refractory disease.