Joaquim Polido-Pereira

Objective: Adverse changes in body composition are increasingly being recognized in patients with rheumatoid arthritis (RA). This study aimed to explore the relationship between RA disease activity, disease impact, and functional disability with bioelectrical phase angle (PhA) and appendicular skeletal muscle mass index (ASMI). Methods: Patients with RA were recruited at a tertiary hospital in Portugal. The Disease Activity Score in 28 joints based on erythrocyte sedimentation rate and C-reactive protein (DAS28-ESR and DAS28-CRP, respectively) were used to assess disease activity. The impact of disease and functional status were evaluated using the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire and the Health Assessment Questionnaire (HAQ), respectively. Body composition was measured by bioelectrical impedance analysis (BIA). PhA was stratified into tertiles, and ASMI was classified according to the European Working Group on Sarcopenia in Older People 2 criteria. Results: A total of 104 patients with RA were included (74% female; mean age 60.9 [SD 9.6] years). RAID scores were significantly lower in patients in the highest PhA tertile (PhA-T3) than in those in the lower PhA tertiles (PhA-T2 and PhA-T1, P = 0.001 and P < 0.001, respectively). HAQ scores were significantly lower in patients in the highest PhA tertile (PhA-T3) than in those in the lowest PhA tertile (PhA-T1, P < 0.001). Median DAS28-ESR and DAS28-CRP were lower among patients with higher PhA, but the difference did not reach statistical significance ( P = 0.07 and P = 0.16, respectively). No differences were found among the ASMI groups in DAS28-ESR ( P = 0.62), DAS28-CRP ( P = 0.97), RAID ( P = 0.30), or HAQ ( P = 0.51) scores. Conclusion: A lower PhA was associated with greater disease impact and greater significant functional disability in patients with RA.

The primary objective was to evaluate the additional benefits of contrast-enhanced ultrasound (CEUS) compared to unenhanced Doppler ultrasound (DUS) for the identification of active synovitis in rheumatoid arthritis (RA). We searched PubMed/MEDLINE and EMBASE (February 2024) for all English-written published reports of human studies including the use of CEUS for the study of synovitis in RA. The risk of bias of included studies was evaluated using the QUADAS tool. DUS and CEUS semiquantitative scores were transformed in binomial, and these data were extracted for meta-analysis. Results that we were unable to quantitatively aggregate were summarised qualitatively. Twenty-three studies using CEUS to evaluate 1117 joints from 827 subjects were included, of which 898 joints were from 669 RA patients. We performed a meta-analysis of 9 studies in active RA patients showing that from 474 joints evaluated by either PDUS/CDUS and CEUS, the synovitis detection was 49.2% and 83.8%, respectively, corresponding to a relative detection ratio (RDR) of 1.49 (95% CI 1.23-1.81) favouring CEUS. Heterogeneity of the data was moderate. In healthy subjects, CEUS detected no vascularisation in 4 studies. CEUS detects more microvascularisation than PDUS in active RA with an RDR of 1.49.

Objective: The study aimed to explore the utility of contrast-enhanced ultrasound (CEUS) as a tool for detecting minimal inflammation in rheumatoid arthritis (RA) patients in sustained remission (SR) and to correlate the findings with Disease Activity Score 28 (DAS28) status scores and various ultrasound (US) scores.Patients and methods: Thirty RA patients in SR (minimum 6 months), 12 with active disease, and 10 healthy controls were included. Clinical evaluations and US assessments were performed, including grayscale US (GSUS), power Doppler US (PDUS), and Global OMERACT-EULAR Synovitis Score (GLOESS). The CEUS was performed in the two most active joints and was scored semi-quantitatively (SQ) and quantitatively.Results: Healthy controls and remission RA patients had similar total US scores. Active RA patients had higher US scores than the healthy and remission groups, with statistically significant differences in all the groups compared to the healthy group. However, significant differences were only observed in the GSUS and GLOESS when comparing active RA patients with the remission group. Ninety-five joints were selected for the CEUS, and we detected more microvascularization with the SQ CEUS score than with the PDUS in all groups (18 vs. 58% in the remission group; p-value 0.006). The weighted Cohen's kappa for the intra-rater and inter-rater IACUS CEUS score was 0.714 (confidence interval 0.610–0.819, p-value < 0.001) and 0.540 (confidence interval: 0.419–0.662, p-value < 0.001), respectively. Spearman's correlation between the SQ CEUS and quantitative scores was 0.655.Conclusion: For the majority of RA patients in SR, conventional US may fail to detect microvascularization potentially related to the subclinical disease. The CEUS may be helpful for this purpose.

Background: Upadacitinib (UPA) 15 mg once daily (QD) has demonstrated efficacy in phase 3 studies of patients with rheumatoid arthritis (RA).1–4 Early prediction of response to treatment with UPA could help to optimize therapy. Objectives: To identify baseline (BL) characteristics or Week (Wk) 12 disease activity measures that may predict the achievement of remission (REM) or low disease activity (LDA) at 6 months in patients with RA receiving UPA 15 mg. Methods: This ad hoc analysis included patients who were randomized to UPA 15 mg QD, as monotherapy in methotrexate (MTX)-naïve patients (SELECT-EARLY) or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in patients with an inadequate response (IR) to MTX (SELECT-COMPARE) or ≥1 tumor necrosis factor inhibitors (TNFis) (SELECT-BEYOND and SELECT-CHOICE). The association of BL characteristics (including age, disease duration, prior/concomitant treatments, C-reactive protein [CRP], seropositivity, and disease activity) and Wk 12 disease activity parameters with the achievement of Clinical Disease Activity Index (CDAI) REM (≤2.8) or LDA (≤10) at Wk 24 (or Wk 26 in SELECT-COMPARE) was assessed by concordance statistics (C-statistics), or area under the receiver operator characteristic curve. C-index values and 95% confidence intervals were calculated by fitting a univariate logistic regression model for: demographic and BL characteristics, Wk 12 disease activity measures, and change from BL at Wk 12 in disease activity measures. A multivariate logistic regression with stepwise model selection was also performed. The proportion of patients achieving Wk 24/26 CDAI REM/LDA was stratified by ≥50% improvement from BL in swollen and/or tender joint count in 66/68 joints (SJC66/TJC68). Results: A total of 1377 patients were included in the analysis. Across the 4 studies, CDAI REM and LDA were achieved in 11.0–28.4% and 50.0–58.6% of patients, respectively (Table 1). BL demographics and disease characteristics were weakly predictive (C-index 0.80) of Wk 24/26 CDAI REM or LDA. Disease Activity Score in 28 joints using CRP and pain at Wk 12 were strongly predictive of Wk 24/26 CDAI REM (except in SELECT-CHOICE). Physician’s global assessment at Wk 12 was the only common predictor in the multivariate regression models for CDAI REM/LDA at Wk 24/26 across the 4 studies. A greater proportion of patients achieving ≥50% improvement in SJC66 and TJC68 at Wk 12 achieved CDAI REM (16.5–37.8% vs 0–9.4%) or LDA (66.0–72.8% vs 20.9–35.7%) at Wk 24/26 than those who did not. Achievement of CDAI LDA and REM at Wk 24/26^a Conclusion: BL characteristics did not strongly predict response to UPA, but composite disease activity scores at Wk 12 predicted Wk 24/26 REM/LDA with UPA 15 mg QD across MTX-naïve, MTX-IR, and TNFi-IR patients. ≥50% improvement in SJC/TJC at Wk 12 was also associated with Wk 24/26 REM/LDA. References: [1]van Vollenhoven R, et al. Arthritis Rheumatol 2020;72:1607–20; 2. Genovese MC, et al. Lancet 2018;391:2513–24; 3. Fleischmann R, et al. Arthritis Rheumatol 2019;71:1788–800; 4. Rubbert-Roth A, et al. N Engl J Med 2020;383:1511–21. Acknowledgements: AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the No honoraria or payments were made for authorship. Medical writing support was provided by Laura Chalmers, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie. Disclosure of Interests: Arthur Kavanaugh Consultant of: Janssen, Grant/research support from: Janssen, Zoltán Szekanecz: None declared, Edward C. Keystone Speakers bureau: Abbott, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Eli Lilly, Genentech, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: Abbott, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Eli Lilly, Genentech, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Abbott, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Eli Lilly, Genentech, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Andrea Rubbert-Roth Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and Sanofi, Stephen Hall Grant/research support from: Pfizer, Ricardo Xavier: None declared, Joaquim Polido-Pereira: None declared, In-Ho Song Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Naomi Martin Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Samuel Anyanwu Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB.

Objective Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a global prevalence of approximately 0.5–1%. Patients with RA are at an increased risk of developing comorbidities (eg, cardiovascular disease, pulmonary disease, diabetes and depression). Despite this, there are limited recommendations for the management and implementation of associated comorbidities. This study aimed to identify good practice interventions in the care of RA and associated comorbidities. Methods A combination of primary research (180+ interviews with specialists across 12 European rheumatology centres) and secondary research (literature review of existing publications and guidelines/recommendations) were used to identify challenges in management and corresponding good practice interventions. Findings were prioritised and reviewed by a group of 18 rheumatology experts including rheumatologists, comorbidity experts, a patient representative and a highly specialised nurse. Results Challenges throughout the patient pathway (including delays in diagnosis and referral, shortage of rheumatologists, limited awareness of primary care professionals) and 18 good practice interventions were identified in the study. The expert group segmented and prioritised interventions according to three distinct stages of the disease: (1) suspected RA, (2) recent diagnosis of RA and (3) established RA. Examples of good practice interventions included enabling self-management (self-monitoring and disease management support, for example, lifestyle adaptations); early arthritis clinic; rapid access to care (online referral, triage, ultrasound-guided diagnosis); dedicated comorbidity specialists; enhanced communication with primary care (hotline, education sessions); and integrating patient registries into daily clinical practice. Conclusion Learning from implementation of good practice interventions in centres across Europe provides an opportunity to more widely improved care for patients with RA and associated comorbidities.

Objective: To study the efficacy, tolerability, safety, and sampling variation of ultrasound (US)–guided synovial biopsies performed in clinical practice and research.Methods: We included all patients who had a US‐guided synovial needle biopsy from November 2013 to January 2018. Patients were evaluated for procedure safety and tolerability. Usefulness of synovial biopsy was considered based on contribution for achieving the proposed aims. We analyzed samples for presence and quality of synovial tissue, synovitis score/grade, and pathotype. Variation across patients, samples, section levels, and sampling order was assessed.Results: A total of 64 US‐guided synovial biopsies were performed (n = 52 in clinical practice, n = 12 in research). Patient tolerability (70% no/mild discomfort) was remarkably high. There was no significant aggravation of symptoms or US synovitis in the biopsied joint. Procedures were overall safe, with few minor, 2 moderate, and no major adverse events. Usefulness of US‐guided synovial biopsies was high, both in clinical practice (37% direct diagnostic impact, 100% positive/95% negative predictive values for infection) and in research (92% success). Synovial tissue was retrieved in 88% of biopsies, with a median of 75% gradable samples. There was significant variation in sample quality and synovitis features across patients and samples, but not between different section levels. Samples collected later in the procedure had a lower frequency of synovial tissue and were poorly concordant in pathotype with those collected earlier.Conclusion: US‐guided synovial needle biopsy is an effective, safe, and well‐tolerated means to collect good quality synovial tissue for clinical and research purposes. Samples collected for different aims should be retrieved in parallel, rather than sequentially.

Ultrasound-guided needle synovial biopsies are useful for clinical practice and research in rheumatology. With the emergence of personalized medicine for the treatment of inflammatory rheumatic diseases, it is predicted that this technique will be increasingly used in the near future. Standardized characterization of the technical aspects of ultrasound-guided needle synovial biopsies is needed in order to produce solid evidence on the safety and effectiveness of the technique.