BackgroundThe Disease Activity Score including 28 joint count (DAS-28) is the most widely used outcome measure in RA. However, despite evidence that metatarsophalangeal (MTP) joints are often the first joints affected in RA, DAS-28 score does not incorporate them.ObjectivesOur study aimed to investigate the correlation between DAS-28 assessment and objective evidence of active joint inflammation using the US examination of both hands and feet, including wrists, metacarpophalangeal (MCP), proximal interphalangeal (PIP), and MTP joints.MethodsA retrospective study was conducted, including 87 patients who were referred to the US clinic for an examination of their hands and feet in the last 6 months (46 patients with RA and 43 controls - patients with other inflammatory or degenerative arthropathies). Information about demographics, disease duration, current treatment, inflammatory markers, and DAS-28 scores was captured. The US OMERACT criteria were used for grading synovial hypertrophy, and assessing for the presence of Power Doppler (PD) signal, erosions and osteophytes. Statistical analysis methods included T-test, Mann-Whitney U test, Z score for proportions and Spearman's correlation coefficients.ResultsIn the RA group, DAS-28 had a weakly positive correlation with the cumulative PD scores of their hands and feet joints (R=0.14, P=0.02), but did not correlate with PD score of MTP joints (R=0.03, P=0.09). In the control group, DAS-28 did not correlate significantly with either the total PD scores of feet (R=0.42, P=0.26) or hands and feet joints (R=0.5, P=0.25). Sensitivity of US examination of hands alone compared to hands and feet was 74.3% for the RA group, while the sensitivity of US feet to detect the presence of PD was 59.2% when compared to the US of both hands and feet.ConclusionsWe found that DAS-28 correlated poorly with objective evidence of inflammation as detected by US of the hands and feet, and this correlation was lost when only the presence of inflammation in the feet was taken into consideration. Further validation of our results in a larger study including patients stratified based on the disease duration might help understand which patient subgroups are more likely to have their disease activity significantly under-evaluated using DAS-28 outcome measure.Disclosure of InterestNone declared

Systemic lupus erythematosus, scleroderma, myositis and Sjögren's syndrome are rare, complex, multi-systemic rheumatic diseases associated with significant morbidity and mortality. Thorough assessments of disease activity are required to guide clinical management and assess response to new therapies in clinical trials. This article reviews the commonly used outcome measures to assess this group of diseases and discusses the limitations of their use.

The most common types of chronic inflammatory arthritis are rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. In order to assess the activity of these diseases and tailor therapy, several outcome measures have been developed. They include composite scores based on clinical findings, biochemical markers and patient questionnaires. This article discusses the most commonly used outcome measures and looks at their limitations in quantifying the complex clinical features of different types of inflammatory arthritis, focusing in particular on rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

Background: SARS-CoV2 infection causes severe, life-threatening pneumonia. Hyper-inflammation, coagulopathy and lymphopenia are associated with pathology and poor outcomes in these patients. Cell-free (cf) chromatin is prominent in COVID-19 patients, amplifies inflammation and promotes coagulopathy and immune dysfunction. We hypothesized that cf-chromatin clearance by nebulised dornase alfa may reduce inflammation and improve disease outcomes. Here, we evaluated the efficacy of nebulized dornase alfa in patients hospitalised with severe COVID-19 pneumonia. Methods: In this randomised controlled single-centre phase 2 proof-of-concept trial, we recruited adult patients admitted to hospital that exhibited stable oxygen saturation (≥94%) on supplementary oxygen and a C-reactive protein (CRP) level ≥30mg/L post dexamethasone treatment. Participants were randomized at a 3:1 ratio to receive twice-daily nebulised dornase alfa in addition to best available care (BAC) or BAC alone for seven days or until hospital discharge. A 2:1 ratio of historical controls to treated individuals (HC, 2:1) were included as the primary endpoint comparators. The primary outcome was a reduction in systemic inflammation measured by blood CRP levels over 7 days post-randomisation, or to discharge if sooner. Secondary and exploratory outcomes included time to discharge, time on oxygen, D-dimer levels, lymphocyte counts and levels of circulating cf-DNA. Results: We screened 75 patients and enrolled 39 participants out of which 30 in dornase alfa arm, and 9 in BAC group. We also matched the recruited patients in the treated group (N=30) to historical controls in the BAC group (N=60). For the the primary outcome, 30 patients in the dornase alfa were compared to 69 patients in the BAC group. Dornase alfa treatment reduced CRP by 33% compared to the BAC group at 7-days (P=0.01). The dornase alfa group least squares mean CRP was 23.23 mg/L (95% CI 17.71 to 30.46) and the BAC group 34.82 mg/L (95% CI 28.55 to 42.47). A significant difference was also observed when only randomised participants were compared. Furthermore, compared to the BAC group, the chance of live discharge was increased by 63% in the dornase alfa group (HR 1.63, 95% CI 1.01 to 2.61, P=0.03), lymphocyte counts were improved (least-square mean: 1.08 vs 0.87, P=0.02) and markers of coagulopathy such as D-dimer were diminished (least-square mean: 570.78 vs 1656.96μg/mL, P=0.004). Moreover, the dornase alfa group exhibited lower circulating cf-DNA levels that correlated with CRP changes over the course of treatment. No differences were recorded in the rates and length of stay in the ICU or the time on oxygen between the groups. Dornase alfa was well-tolerated with no serious adverse events reported. Conclusions: In this proof-of-concept study in patients with severe COVID-19 pneumonia, treatment with nebulised dornase alfa resulted in a significant reduction in inflammation, markers of immune pathology and time to discharge. The effectiveness of dornase alfa in patients with acute respiratory infection and inflammation should be investigated further in larger trials. Trial registration number: NCT04359654