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Objectives: To assess the sensitivity to change of ultrasound halo features and their association with disease activity and glucocorticoid (GC) treatment in patients with newly diagnosed giant cell arteritis (GCA).Methods: Prospective study of patients with ultrasound-confirmed GCA who underwent serial ultrasound assessments of the temporal artery (TA) and axillary artery (AX) at fixed time points. The number of segments with halo and maximum halo intima-media thickness (IMT) was recorded. Time points in which >80% of patients were assessed were considered for analysis. Halo features at disease presentation and first relapse were compared.Results: 49 patients were assessed at 354 visits. Halo sensitivity to change was assessed at weeks 1, 3, 6, 12 and 24 and showed a significant standardised mean difference between all time points and baseline for the TA halo features but only after week 6 for the AX halo features. The number of TA segments with halo and sum and maximum TA halo IMT showed a significant correlation with erythrocyte sedimentation rate (0.41, 0.44 and 0.48), C reactive protein (0.34, 0.39 and 0.41), Birmingham Vasculitis Activity Score (0.29, 0.36 and 0.35) and GC cumulative dose (-0.34, -0.37 and -0.32); no significant correlation was found for the AX halo features. Halo sign was present in 94% of first disease relapses but with a lower mean number of segments with halo and sum of halo IMT compared with disease onset (2.93±1.59 mm vs 4.85±1.51 mm, p=0.0012; 2.01±1.13 mm vs 4.49±1.95 mm, p=0.0012).Conclusions: Ultrasound is a useful imaging tool to assess disease activity and response to treatment in patients with GCA. [ABSTRACT FROM AUTHOR]

Objectives: To compare consecutive disease modifying antirheumatic drug (DMARD)-treatment regimes in daily practice in patients with rheumatoid arthritis (RA) who failed on initial methotrexate, while using a multiple propensity score (PS) method to control for the spurious effects of confounding by indication.Methods: Patients with newly diagnosed RA who had failed initial treatment with methotrexate were selected from METEOR, an international, observational registry. Subsequent DMARD-treatment regimens were categorised as: (1) conventional synthetic DMARD(s) (csDMARD(s)) only (143 patients), (2) csDMARD(s)+glucocorticoid (278 patients) and (3) biological DMARD (bDMARD)±csDMARD(s) (89 patients). Multiple PS that reflect the likelihood of treatment with each treatment-regime were estimated per patient using multinomial regression. Linear mixed model analyses were performed to analyse treatment responses per category (Disease Activity Score (DAS)) after a maximum follow-up duration of 6 and 12 months, and results were presented with adjustment for the multiple PS.Results: After 6 months, follow-up PS-adjusted treatment responses yielded a change in DAS per year (95%  CI) of -2.00 (-2.65 to -1.36) if patients received a bDMARD; of -0.96 (-1.33 to -0.59) if patients received csDMARD(s)+glucocorticoids and of -0.73 (-1.21 to -0.25) if patients received csDMARDs only. These changes were -0.91 (-1.23 to -0.60); -0.43 (-0.62 to -0.23) and -0.39 (-0.66 to -0.13), respectively after 1  year of follow-up.Conclusions: In this analysis of worldwide common practice data with adjustment for multiple PS, patients with RA who had failed initial treatment with methotrexate monotherapy had a better DAS-response after a subsequent switch to a bDMARD-containing treatment regimen than to a regimen with csDMARD(s) only, with or without glucocorticoids. [ABSTRACT FROM AUTHOR]

Background We have previously reported an increase in interleukin (IL)-1β levels in very recent onset arthritis. Therefore, molecular mechanisms that regulate IL-1β secretion, such as caspase-1 activation, might play a relevant role in arthritis onset and progression. Objectives Our main goal was to evaluate caspase-1 state of activation in early polyarthritis and established rheumatoid arthritis (RA) patients. Materials and methods Blood samples were collected from 12 untreated early polyarthritis patients, 12 established RA patients and 10 healthy controls. Caspase-1 activity was assessed using a carboxyfluorescein FLICA detection kit. Results We found that both early polyarthritis and established RA patients have higher active caspase-1 levels. Surprisingly, caspase-1 activation levels in patient cells remain unchanged when cells were stimulated with and ATP, whereas in control cells caspase-1 levels increased after stimulation. We observed no significant differences when comparing early polyarthritis with established RA samples. However, in RA patients with higher disease activity the proportion of active caspase-1 is higher. Conclusions Our results suggest that leucocytes in both early polyarthritis and established RA patients have high baseline levels of activated caspase-1, which cannot be significantly increased after stimulation. Altogether, our data supports the hypothesis that caspase-1 is activated in early arthritis. [ABSTRACT FROM PUBLISHER]

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease where the excessive secretion of pro-inflammatory cytokines plays an important role. The authors have previously reported an increase in circulating interleukin 1β (IL-1β) levels in very recent onset arthritis and in the synovial fluid of established RA patients. This observation may be explained by the continuous activation of caspase-1 that the authors observed both in early polyarthritis and in established RA patients. Therefore, pathways that regulate IL-1β, such as caspase-1 and nuclear factor-κB (NF-κB) activation, might play a relevant role in arthritis onset and drugs that target these pathways could potentially constitute promising therapeutic agents in RA. The authors have thus used a THP1 macrophage-like cell line to screen among several Food and Drug Administration approved drugs those which downregulate IL-1β and caspase-1 activation. Gambogic acid and celastrol were two of the most promising therapeutic candidates obtained by this screening. Objectives The study main goal was to investigate whether gambogic acid and celastrol administration is able to attenuate inflammation in a rat model of antigen-induced arthritis (wistar AIA rat). Materials and methods Drugs and vehicle control were administrated to arthritic wistar AIA rats after 4 days of disease induction for a period of 15 days. The inflammatory score, paw diameter and body weight were evaluated during the time of treatment. Rats were killed after 19 days of disease evolution and paw samples were collected for histology observation of erosions, pannus formation and cellular infiltration. Results The authors found that both gambogic acid and celastrol significantly suppressed inflammation in the joints in comparison with arthritic rats treated with vehicle only. Moreover, the rats treated with these drugs did not show differences in body weight or other evident side effects. The histology results revealed that gambogic acid and celastrol treated rats showed a normal joint structure with a complete abrogation of the inflammatory infiltrate. Conclusions This results suggest that both drugs have significant anti-inflammatory properties, in agreement with their reported ability to suppress NF-κB activation. Gambogic acid and celastrol might therefore constitute putative anti-inflammatory drugs with therapeutic efficacy in the treatment of inflammatory diseases, such as RA. [ABSTRACT FROM PUBLISHER]

Background B cells play several important roles in rheumatoid arthritis (RA). Previous studies by our group have demonstrated that very early rheumatoid arthritis (VERA) patients have disturbances in peripheral blood memory B cells and increased circulating B cell related cytokines. Objectives The main goal of this work was to analyse the expression of genes related with B cell survival and activation in VERA (<6 weeks of disease duration) and compare with early RA (<1 year, ERA), established RA patients (RA) and other early arthritis conditions (VEA) to identify differences between disease stages. Materials and methods BAFF, BAFF-R, TACI, BCMA, AID, CXCR5, Pax5, Blimp-1, β2m and Bcl-2 mRNA levels from peripheral blood mononuclear cell (PBMC) were determined by real-time PCR. Serum BAFF was quantified by ELISA. Results VERA patients had increased BAFF and TACI mRNA levels in comparison with controls. Moreover, BAFF mRNA expression was higher in VERA in comparison with RA and VEA patients. BAFF-R expression was elevated in ERA and RA when compared to controls. Pax5 expression was increased in all RA patients and reduced in VEA in comparison with VERA. β2m levels were elevated in VERA, ERA and VEA patients when compared to controls. No differences were observed in BCMA, AID, CXCR5, Blimp-1 and Bcl-2 expression. Furthermore, VERA patients had the highest serum BAFF levels. Conclusions Disturbances in the expression of B cell related activation genes, particularly BAFF and TACI, occur since the very early phase of RA. The increased BAFF serum and mRNA levels occurring in VERA patients might indicate BAFF as a potential therapeutic target since the first weeks of RA onset. [ABSTRACT FROM PUBLISHER]

Objectives: To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field., Methods: An international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item., Results: The task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3-6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations., Conclusions: These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)