[18F]FDG PET/CT for therapeutic assessment of Abatacept in early-onset polymyalgia rheumatica.

PURPOSE: Evaluate the benefit of 2-deoxy-2-[18F]-fluoro-D-glucose ([18F] FDG) positron emission tomography/computed tomography (PET/CT) for the therapeutic assessment of Abatacept (ABA) as first-line therapy in early-onset polymyalgia rheumatica (PMR) patients. METHODS: This was an ancillary study of ALORS trial (Abatacept in earLy Onset polymyalgia Rheumatica Study) assessing the ability of ABA versus placebo to achieve low disease activity (C-Reactive Protein PMR activity score (CRP PMR-AS) ≤ to 10) without glucocorticoid (GC) at week 12 in patients with early-onset PMR. The patients underwent [18F] FDG PET/CT at baseline and after 12 weeks of treatment. Responses to treatments were evaluated according to CRP PMR-AS, Erythrocyte Sedimentation Rate (ESR) PMR-AS, Clin PMR-AS, and CRP-Imputed (Imput-CRP) PMR-AS. Quantitative score by maximal standardized uptake value (SUVmax) and combined qualitative scores according to liver uptake (Leuven, Leuven/Groningen, and Besançon Scores) were used for assessment of [18F] FDG uptake in regions of interest (ROI) usually affected in PMR. Student's t-test was applied to evaluate the clinical, biological, and [18F] FDG uptake variation difference in ABA and placebo groups between W0 and W12. Subgroup analysis by GC rescue was performed. RESULTS: At W12, there was no significant difference according to SUVmax between the ABA and the placebo groups in all ROI. Subgroup analysis according to GC administration demonstrated a significant (p 0.047) decrease in SUVmax within the left sternoclavicular joint ROI in the ABA group (- 0.8) compared to the placebo group (+ 0.6) without GC rescue. Other results did not reveal any significant difference between the ABA and placebo groups. According to combined qualitative scores, there was no significant difference between ABA and placebo groups for the direct comparison analysis and subgroup analysis according to GC rescue. CONCLUSION: [18F] FDG PET/CT uptake did not decrease significantly after ABA compared to placebo in anatomical areas usually affected in PMR patients. These results are correlated with the clinical-biological therapeutic assessment. CLINICAL TRIAL REGISTRATION: The study was approved by the appropriate ethics committee (CPP Sud-Est II Ref CPP: 2018-33), and all patients gave their written informed consent before study enrollment. The protocol was registered on Clinicaltrials.gov (NCT03632187).

Screening for and management of comorbidities after a nurse-led program: results of a 3-year longitudinal study in 769 established rheumatoid arthritis patients.

Background/purpose: Cardiovascular (CV) risk, cancer, infections and osteoporosis should be screened for in rheumatoid arthritis (RA). The objective was to assess 3-year effects of a nurse visit for comorbidity counselling. Methods: This was an open long-term (3 years) extension of the Comorbidities and Education in Rheumatoid Arthritis 6-month randomised controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity counselling. Comorbidity status was assessed and nurses provided advice on screening and management, at baseline and 3 years later. A score was developed to quantify comorbidity screening and management: 0-100, where lower scores indicate better screening and management. The score was compared between baseline and 3-year assessment using a Wilcoxon test for paired data. Results: Of the 970 recruited patients, 776 (80%) were followed-up at 2-4 years and 769 (79%) had available data for comorbidities at both time points: mean (±SD) age 58 (±11) years and mean disease duration 14 (±10) years; 614 (80%) were women, the mean Disease Activity Score 28 was 3.0±1.3, and 538 (70%) were receiving a biologic. At baseline, the mean comorbidity screening score was 36.6 (±19.9) and it improved at 3 years to 24.3 (±17.8) (p<0.0001), thus with a relative improvement of 33% (improvement of 12 points). CV risk screening, vaccination status and bone densitometry performance improved the most. Conclusions: Comorbidity screening was suboptimal but improved notably over 3 years, after a nurse-led programme aiming at checking systematically for comorbidity screening and giving patient advice. This long-term efficacy pleads in favour of nurse-led interventions to better address comorbidities in RA. Trial registration number: NCT01315652.

Assessment of major salivary gland size in primary Sjögren's syndrome: Comparison between clinical examination and ultrasonography.

OBJECTIVE: Parotidomegaly is a criterion of the EULAR Primary Sjögren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous. The objective is to evaluate inter-observer reproducibility of parotid gland measurement by palpation, and to secondary evaluate its reliability compared to US assessment. METHODS: Outpatients with primary Sjögren Syndrome (pSS) or with a diagnostic suspicion, in a single reference centre, were included. They underwent clinical examination by two independent investigators (VDP and DC), evaluating: parotid gland swelling, parotid gland size (direct measurement with a decameter under the mandibular angle), and pain. Cohen's kappa coefficient was calculated to determine inter-observer concordance for parotid gland swelling, and intraclass correlation coefficient to determine inter-observer agreement of gland size measurement. RESULTS: Thirty-four patients (33 women, 1 man) were included. Clinical data were complete for 33 patients. Inter-observer concordance Kappa coefficient was 0.90 [0.76-1.00] for detection of parotidomegaly over 66 parotid glands. It was of 0.60 [0.42-0.73] for gland length measurement. For one observer, the median cut-off for defining parotidomegaly was 4.15 cm; for the second observer, it was of 4.92 cm. For submandibular glands palpation, no correlation was found between investigators. A significant association between clinical parotidomegaly and a larger echographic surface was found. CONCLUSION: Clinical measurement of parotidomegaly was concordant between two observers on a binary mode (presence/absence). However, concordance on direct measurement was weak. US could be a complementary examination.

Brief Report: Ultrasonographic Assessment of Salivary Gland Response to Rituximab in Primary Sjögren's Syndrome.

OBJECTIVE: To evaluate changes in salivary gland echostructure and vascularization after rituximab treatment in patients with primary Sjögren's syndrome (SS). METHODS: Twenty-eight patients with primary SS included in the multicenter, randomized, double-blind, placebo-controlled Tolerance and Efficacy of Rituximab in Primary Sjögren's Syndrome (TEARS) trial underwent salivary gland ultrasonography before the first placebo or rituximab infusion and then 6 months later. Trial inclusion criteria were scores of ≥50 mm on at least 2 of 4 visual analog scales (VAS) evaluating dryness, pain, fatigue, and global disease; and recent-onset (<10 years) biologically active primary SS and/or systemic primary SS. Patients were randomly assigned (1:1) to rituximab (1 gm at weeks 0 and 2) or placebo. Ultrasonography of both parotid and submandibular glands was performed to assess echostructure (using a semiquantitative score of 0-4, with improvement defined as a ≥1-point decrease), size of each gland, and vascularization based on the resistive index of the transverse facial artery of the parotid gland before and after lemon juice stimulation. RESULTS: Of the 28 patients, 5 (18%; 3 in the placebo group and 2 in the rituximab group) had clinically detectable bilateral parotid gland enlargement at baseline. Parotid parenchyma echostructure improved in 50% of the rituximab-treated patients versus 7% of the placebo-treated patients (P = 0.03). In the submandibular glands, echostructure also improved in a larger proportion of rituximab-treated patients, although the difference was not significant (36% versus 7% of placebo-treated patients; P = 0.16). Gland sizes and resistive index remained unchanged. CONCLUSION: Ultrasonography showed improved salivary gland echostructure in patients with primary SS receiving rituximab, with no changes in salivary gland size or vascularization, 6 months after the first infusion.

The learning curve of nurses for the assessment of swollen and tender joints in rheumatoid arthritis.

OBJECTIVES: In rheumatoid arthritis (RA), nurses are now increasingly involved in joint count assessment but training is not standardized. The aim was to evaluate and describe the learning curve of nurses for the assessment of swollen and tender joints in RA. METHOD: Twenty nurses from university rheumatology centres inexperienced with joint counts were allocated to a rheumatologist from their centre (teacher). Acquisition of skills consisted of Phase 1: (training), a centralized 4hour training session, with (a) lecture and demonstration, and (b) practical sessions on patients with their teachers, followed by Phase 2: (practice) involving further practice on 20 patients in their own hospitals. Primary outcome was achievement of adequate swollen joint agreement between nurse and their teacher ("gold standard") at the "joint" level defined by prevalence adjusted biased adjusted kappa (PABAK)>0.60. Agreement at the "patient" level of swollen joint count (SJC), tender joint count (TJC) as well as DAS28 between nurse and their teacher were assessed with intra-class correlation coefficients (ICC). RESULTS: During the training phase, 75% of nurses achieved a swollen joint PABAK>0.60 when compared with their teachers, which further improved to 89% after the 20 practice patients (Phase 2). Median swollen joint PABAK improved from 0.64 (Q1:Q3 0.55,0.86) to 0.83 (Q1:Q3 0.77,1) by the end of Phase 2. At the "patient" level, SJC agreement remained globally stable (ICC, 0.52 to 0.66), while TJC and DAS28 agreement remained excellent throughout. CONCLUSION: Nurses inexperienced in joint counts were able to achieve excellent agreement with their teachers in assessment of tender and swollen joints through a short training session; practice further enhanced this agreement. Larger longitudinal studies are required to assess skills retention.

Improving agreement in assessment of synovitis in rheumatoid arthritis.

OBJECTIVE: Synovitis assessment through evaluation of swollen joints is integral in steering treatment decisions in rheumatoid arthritis (RA). However, there is high inter-observer variation. The objective was to assess if a short collegiate consensus would improve swollen joint agreement between rheumatologists and whether this was affected by experience. METHODS: Eighteen rheumatologists from French university rheumatology units participated in three 30 minutes rounds over a half day meeting evaluating joint counts of RA patients in small groups, followed by short consensus discussions. Agreement was evaluated at the end of each round as follows: (i) global agreement of swollen joints (ii) swollen joint agreement according to level of experience of the rheumatologist (iii) swollen joint count and (iv) agreement of disease activity state according to the Disease Activity Score (DAS28). Agreement was calculated using percentage agreement and kappa. RESULTS: Global agreement of swollen joints failed to improve (kappa 0.50 to 0.52) at the joint level. Agreement between seniors did not improve but agreement between newly qualified rheumatologists and their senior peer, which was initially poor (kappa 0.28), improved significantly (to 0.54) at the end of the consensus exercises. Concordance of DAS28 activity states improved from 71% to 87%. CONCLUSION: Consensus exercises for swollen joint assessment is worthwhile and may potentially improve agreement between clinicians in clinical synovitis and disease activity state, benefit was mostly observed in newly qualified rheumatologists.

Reproducibility of joint swelling assessment by sonography in patients with long-lasting rheumatoid arthritis (SEA-Repro study part II).

OBJECTIVE: To evaluate the intraobserver and interobserver reproducibility of B-mode and power Doppler (PD) sonography in patients with active long-standing rheumatoid arthritis (RA) comparatively with clinical data. METHODS: In each of 7 patients being considered for a change in their RA treatment regimen, 7 healthcare professionals examined the 28 joints used in the Disease Activity Score 28-joint count (DAS28). Then 7 sonographers examined each of the 7 patients twice, using previously published B-mode and PD grading systems. The clinical reference standard was presence of synovitis according to at least 4/7 examiners. The sonographic reference standard was at least grade 1 (ALG1) or 2 (ALG2) synovitis according to at least 4/7 sonographers. Interobserver reproducibility of sonography was assessed versus the sonographer having the best intraobserver reproducibility. Agreement was measured by Cohen's kappa statistic. RESULTS: Intraobserver and interobserver reproducibility of B-mode and PD used separately was fair to good. Agreement between clinicians and sonographers at all sites using B-mode, PD, and both was 0.46, 0.37, and 0.36, respectively, for grade 1 synovitis; and 0.58, 0.19, and 0.19 for grade 2 synovitis. The number of joints with synovitis was smaller by physical examination (36.7%) than by B-mode with ALG1 (58.6%; p < 0.001). The number of joints with synovitis was higher by physical examination than by PD with both ALG1 (17.8%; p < 0.0001) and ALG2 (6.6%; p < 0.0001). CONCLUSION: PD findings explain most of the difference between clinical and sonographic joint assessments for synovitis in patients with long-standing RA.