M. Montoro

Ultrasound joint inflammation in rheumatoid arthritis in clinical remission: how many and which joints should be assessed?

To investigate the sensitivity for detecting subclinical synovitis of different reduced joint ultrasound (US) assessment models as compared with a comprehensive US assessment in rheumatoid arthritis (RA) patients in clinical remission.

Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis

OBJECTIVE To investigate the predictive value of synovitis detected by Doppler US in relation to failed tapering of biologic therapy (BT) in RA patients in sustained clinical remission. METHODS A total of 77 RA patients (52 women, 25 men) in sustained clinical remission, treated with a stable dosage of BT were prospectively recruited. BT was tapered according to an agreed strategy implemented in clinical practice (i.e. increasing the interval between doses for s.c. BT and reducing the dose for i.v. BT). BT tapering failure was assessed at 6 and 12 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy and synovial power Doppler signal (i.e. Doppler synovitis) was performed at baseline by a rheumatologist blinded to clinical and laboratory data. Hand and foot radiographs were obtained at baseline and at 12-month follow-up. RESULTS Of the 77 patients, 46 (59.7%) were on s.c. BT and 31 (40.3%) on i.v. BT. At 12 months, 35 patients (45.5%) presented BT tapering failure, 23 of them (29.9% of all patients) in the first 6 months of BT tapering. In logistic regression analysis, the baseline DAS28 and the global score of Doppler synovitis were identified as independent predictors of BT tapering failure at 12 and 6 months. The presence of Doppler synovitis was the strongest predictor for BT tapering failure. No patient showed radiographic progression. CONCLUSION Our results suggest that the presence of Doppler-detected synovitis may predict BT tapering failure in RA patients in sustained clinical remission.

Patient self-assessment and physician’s assessment of rheumatoid arthritis activity: which is more realistic in remission status? A comparison with ultrasonography

OBJECTIVE The objective of this study was to compare disease activity assessed by the patient, the physician and musculoskeletal US in patients with RA in clinical remission. METHODS We evaluated 69 patients with RA in clinical remission according to their attending rheumatologist. Tenderness and swelling in 28 joints were blindly assessed by patients and physicians. The presence of B-mode and Doppler synovitis was blindly investigated in the above joints. The DAS28 and Simplified Disease Activity Index (SDAI) were calculated. RESULTS The percentage of patients in remission according to the self-derived DAS28 (26.1%) was significantly less than that according to the physician-derived DAS28 (52.2%) (P < 0.0005). There was no significant difference in the percentage of patients in remission according to the self-derived SDAI (14.5%) and the physician-derived SDAI (11.6%) (P = 0.172). We found moderate agreement between the patient-derived and physician-derived DAS28 and SDAI [intraclass correlation coefficient (ICC) = 0.620 and ICC = 0.678, respectively]. Agreement between patient and physician was better for the tender joint count (TJC; ICC = 0.509) than for the swollen joint count (SJC; ICC = 0.279). The mean (S.D.) count for B-mode synovitis [4.09 (3.25)] was significantly greater than the SJC assessed by both the patient and physician [2 (3.71) and 1.42 (2.03), respectively] (P < 0.0005 and P = 0.033, respectively). We found moderate agreement between the physician-assessed SJC and the joint count for Doppler synovitis (ICC = 0.528). CONCLUSION Patient-assessed and physician-assessed overall RA activity showed acceptable agreement. Patient self-assessment overestimated disease activity determined by the DAS28. At the patient level, physician-assessed joint swelling showed an acceptable concordance with Doppler US synovitis.

Anti-TNF treatments in rheumatoid arthritis: economic impact of dosage modification

Rheumatoid arthritis (RA) is a chronic systemic disease that leads to increases in health system economic burden through direct and indirect costs, including chronic treatment, reduced productivity and premature mortality. Anti-TNF agents have represented a major advance in the treatment of RA. The most commonly used (adalimumab, etanercept and infliximab) have demonstrated their cost–effectiveness at label doses. However, physicians may need to adapt the treatment by increasing the dose when a drug is not effective enough or by reducing it when there is a sustained effectiveness. In a cross-sectional study conducted in our hospital in which information from RA patients treated with anti-TNF drugs under conventional and modified doses were collected, the authors analyzed the costs of the medication in order to estimate the mean patient-year cost, the annual costs related to clinical efficacy and the cost per responder patient to anti-TNF treatment when dosage modification is undertaken in daily clinical practice.

Long-term remission of severe refractory dermatopolymyositis with a weekly-scheme of immunoglobulin followed by rituximab therapy

We report on a 44-year-old woman affected by dermatopolymyositis resistant to conventional therapies who experienced long-term clinical improvement and remission after treatment with intravenous polyvalent immunoglobulin in a weekly schedule followed by rituximab therapy.

Multiobserver Reliability of Ultrasound Assessment of Salivary Glands in Patients with Established Primary Sjögren Syndrome

Objective. To evaluate the multiobserver reliability of salivary gland ultrasonography (SGUS) for scoring greyscale (GS) parenchymal inhomogeneity and parenchymal color Doppler (CD) signal in patients with established primary Sjögren syndrome (pSS). Methods. The study comprised 2 multiobserver reliability assessments in patients with pSS in 2 European centers. The first reliability exercise was performed on 24 patients with pSS and 8 controls who were independently evaluated with GS and CD US by 5 observers at the Institute of Rheumatology, Belgrade, Serbia. The second reliability exercise was carried out on 10 patients with pSS who were independently assessed with GS and CD US by 8 observers at the Hospital G.U. Gregorio Marañón, Madrid, Spain. SGUS parenchymal inhomogeneity and parenchymal CD signal were semiquantitatively scored using a 4-grade scoring system. The multiobserver agreement was calculated by the overall agreement and Light’s κ statistics. Results. A total of 640 SGUS examinations were performed in the first reliability exercise and a total of 320 examinations in the second reliability exercise. Multiobserver reliability was good (κ = 0.71–0.79) to excellent (κ = 0.81–0.82) for GS parenchymal inhomogeneity in both exercises. There was a moderate (κ = 0.53–0.58) to good (κ = 0.70) multiobserver reliability for parenchymal CD signal in the first exercise. However, there was no agreement or only a fair agreement (κ = 0.03–0.29) for parenchymal CD signal in the second exercise. Conclusion. US may be a reliable technique in the multiobserver scoring of GS parenchymal inhomogeneity of major SG in patients with established pSS. CD scoring of SG needs further standardization to be used in multicenter studies.

Minimum Effective Dosages of Anti-TNF in Rheumatoid Arthritis: A Cross-sectional Study

AIMS To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. PATIENTS AND METHODS Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. MAIN VARIABLES dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. RESULTS 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). CONCLUSIONS RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients.

Does ultrasound-scored synovitis depend on the pharmacokinetics of subcutaneous anti-TNF agents in patients with rheumatoid arthritis?

OBJECTIVE The aim of this study was to investigate the influence of the pharmacokinetics of s.c. anti-TNF agents on the grade of US-detected synovitis in RA patients. METHODS Fifty RA patients were prospectively recruited from the Biologic Therapy Unit of our hospital. Inclusion criteria were being in treatment with s.c. anti-TNF agents and having had neither changes in therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory [28-joint DAS (DAS28) and Simplified Disease Activity Index (SDAI)] and US assessment at two time points, i.e. at peak plasma drug concentration and at trough plasma drug concentration. US assessments were performed blindly to the anti-TNF agent, the administration time and the clinical and laboratory data. Twenty-eight joints were investigated for the presence and grade (0-3) of B-mode synovitis and synovial power Doppler signal. Global indices for B-mode synovitis (BSI) and Doppler synovitis (DSI) were calculated for 12 joints and for wrist-hand-ankle-foot joints. B-mode US remission was defined as a BSI <1 and Doppler US remission as a DSI <1. RESULTS There were no significant differences between the clinical, laboratory and B-mode and Doppler US parameters at peak time and trough time (P = 0.132-0.986). There were no significant differences between the proportion of patients with active disease and those in remission according to DAS28, SDAI, B-mode US and Doppler US at peak time and trough time assessments (P = 0.070-1). CONCLUSION Our results suggested that s.c. anti-TNF pharmacokinetics do not significantly influence US-scored synovitis in RA patients.

Brief ReportMinimum Effective Dosages of Anti-TNF in Rheumatoid Arthritis: A Cross-sectional StudyDosis efectiva mínimas de anti-TNF en artritis reumatoide: un estudio transversal

Aims To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR.

AB0396 Infliximab and Adalimumab Levels and Antidrug Antibodies Detection in Patients with Rheumatoid Arthritis (RA): an Interlaboratory Comparison Using A Commercial ELISA Assay

Background The assessment of biological drug levels and immunogenicity might be essential in terms of a more effective and rational use of biological therapies and it is dependent upon the establishment of efficient standardized assays or a consensus that could allow a direct comparison of drug levels and anti-drug antibodies (ADA) data with clinical outcome. Objectives To determine whether an enzyme-linked immunosorbent assay (ELISA) performed with two versions of a commercial kit to assess IFX and ADL levels and ADA yield similar results. Methods The diagnostic capability of two ELISA versions [Promonitor® IFX R1 and R2 (V.1), Promonitor® IFX and Anti-IFX (V.2); Promonitor® ADL R1 and R2 (V.1), Promonitor® ADL and Anti-ADL (V.2) kits (Progenika Biopharma, Spain)] was evaluated in patients with RA treated either with infliximab (IFX; n=24) or adalimumab (ADL; n=24) by three different laboratories. The reliability was determined using the Cohens Kappa coefficient (K), the Pearsons r, the intraclass correlation coefficient (ICC) and the Lins concordance correlation coefficient (CCC). The Bland-Altman plots of differences between V.1 and V.2 were drawn to compare values of each assay. Results The qualitative discordant results for IFX levels V.1 were 9/24 samples (K= good) and 2/23 V.2 (K= very good), for ADL levels V.1 were 7/24 (K= moderate) and for V.2 were 0/24 (K= very good). For IFX-ADA were 0/24 in V.1 and V.2 (K= excellent), while for ADL-ADA were 1/24 in V.1 and 4/24 in V.2 (K= from very good to good). The quantitative agreement is shown in table 1, we found a good linear association using the Pearsons r, the ICC was questionable to excellent for both versions in IFX and ADL levels. The CCC results were poor in all determinations. Bland-Altman plots for both, IFX and ADL levels demonstrate the differences between both versions (Fig. 1 and 2, respectively). Conclusions We observed a better agreement in the qualitative than in the quantitative results in both, for IFX and ADL levels and for IFX-ADA and ADL-ADA. We have found a good linear association (Pearsons r) but a low agreement (K, ICC and CCC) comparing results for V.1 and V.2. Further interlaboratory investigations are necessary to improve results and determine their possible clinical application. Disclosure of Interest L. Valor: None declared, D. Hernández Flόrez: None declared, I. de la Torre: None declared, F. Llinares: None declared, J. Rosas: None declared, J. Yaque: None declared, E. Naredo Grant/research support: UCB and MSD, Consultant for: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, and Esaote, C. Gonzalez: None declared, J. Lόpez-Longo: None declared, I. Monteagudo Consultant for: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, MSD and Esaote, M. Montoro: None declared, L. Carreño Perez: None declared DOI 10.1136/annrheumdis-2014-eular.3290