Juan Carlos Nieto

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.

Toward standardized musculoskeletal ultrasound in pediatric rheumatology: Normal age related ultrasound findings

The Outcome Measures in Rheumatology Ultrasound Task Force has recently started to work on the validation and standardization of musculoskeletal ultrasound (MSUS) examination in children in order to improve its applicability to joint examination.

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.

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.

Age-related vascularization and ossification of joints in children: an international pilot study to test multi-observer ultrasound reliability

To determine the intra‐ and interobserver reliability of ultrasound (US)‐detected age‐related joint vascularization and ossification grading in healthy children.

SAT0509 Clinical and Serological Profile of Children with Positive SSA-Ro/SSB-La Antibodies

Background Several studies have shown the relationship between anti-SSA-Ro/SSB-La antibodies and Systemic Lupus Erythematosus (SLE), Sjögren Syndrome (SS) and other autoimmune diseases in adult population. However, the expression of these autoantibodies and clinical correlation in juvenile patients is poorly described. Objectives To characterize the clinical and serological profile and primary rheumatic diseases in pediatric patients with positive anti-SSA-Ro and/or anti-SSB-La antibodies. Methods The data was obtained from a long term prospective cohort of patients under age 18 diagnosed with rheumatic diseases in a tertiary hospital in Spain. Demographic, clinical, and laboratory data were collected from 1986 to 2010. Patients were divided into 2 groups: anti-SSA-Ro/SSB-La positive and anti-SSA-Ro/SSB-La negative. Results A total of 187 patients were tested for anti Extractable Nuclear Antigens (ENA), with a following mean time of 11 years. Mean age at disease onset was 12.6 years and 77% were female. Fifty-four (28.9%) anti-SSA-Ro/SSB-La positive subjects were compared against 133 (71.1%) anti-SSA-Ro/SSB-La negative subjects. Among positive cases, 13 (24.1%) patients were double-positive for anti-SSA-Ro and anti-SSB-La, 51 (94.4%) were positive for anti-SSA-Ro and 3 (5.5%) were single-positive for anti-SSB-La. The anti-SSA-Ro/SSB-La antibodies were found less frequently (p=0.003) in the overlapping syndromes, and more frequently in SLE (p=0.007). In addition rheumatoid factor (p<0.001), anti-Sm (p<0.001) and anti-RNP (p<0.001) were frequently co-expressed with anti-SSA-Ro/SSB-La antibodies. Finally the anti-SSA-Ro/SSB-La positive group presented more hematological and skin manifestations than the negative group (p<0.05). Conclusions Similarly to adults, we observed a relationship between anti-SSA-Ro/SSB-La antibodies and SLE in pediatric patients. However a low proportion of childhood primary SS exists in our anti-SSA-Ro/SSB-La positive cases. This could be explained by underdiagnoses related to the atypical clinical presentation of SS in pediatric population. Single-positive anti-SSB-La patients are uncommon, the clinical significance of this serological result remains uncertain in children. References Rheumatol Int (2014) 34:1123–1127. Disclosure of Interest None declared

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.

SAT0340 Infliximab Levels and Anti-Infliximab Antibodies Comparison between Two Comercial ELISA Versions in Patients with Ankylosing Spondylitis

Background Ankylosing spondylitis (AS) is a chronic inflammatory disease which can result in invalidating deformities of the joints and spine at an early age. The introduction of tumor necrosis factor (TNF) blocking agents has changed the treatment options in AS. Nevertheless, the reasons for lack or loss of response to infliximab (IFX) are unclear. So far determinations of both, IFX serum levels and the presence of anti-drug antibodies (ADA) anti-IFX have not been standardized for clinical use. Objectives To assess the correlation between two available versions (V.1 and V.2) of a commercial enzyme-linked immunosorbent assay (ELISA) for serum levels of IFX and IFX-ADA in patients with AS. Methods In this cross sectional study we assessed 40 serum samples taken prior to infusion from patients diagnosed with AS treated with IFX for more than 12 months (1st line of biological treatment). IFX levels and IFX-ADA were measured using two different ELISA assays [Promonitor® IFX R1 and R2 (V.1), Promonitor® IFX and Anti-IFX (V.2) (Progenika Biopharma, Spain)] according to manufacturers specifications. The relation comparing V.1 and V.2 for IFX levels and IFX-ADA concentrations was performed using the coefficient of variation (CV), the Cohens Kappa coefficient, the Pearsons r, the intraclass correlation coefficient (ICC) and the Lins concordance correlation coefficient (CCC). Bland-Altman plots were drawn to compare both versions of the assays. Results As shown in the table below, we found a greater CV for IFX levels than for IFX-ADA. Regarding the qualitative results the Cohens Kappa was from moderate to fair and considering the quantitative results the Pearsons r was low for IFX levels and high for IFX-ADA, the ICC was questionable for both versions and both determinations. We also determined the CCC and the results showed a poor agreement. Bland-Altman plots showed the difference between both versions for IFX levels (Fig. 1). Conclusions A low reliability for IFX levels and IFX-ADA was obtained for both versions. There is a need to standardize laboratory techniques (variability inter/intra-assay and inter/intra-laboratory) in order to validate this information and its possible clinical application. Disclosure of Interest D. Hernández Flόrez: None declared, L. Valor: None declared, J. C. Nieto: None declared, L. Martinez: None declared, I. de la Torre: None declared, T. del Río: None declared, C. Gonzalez: None declared, J. Lopez-Longo: None declared, I. Monteagudo Consultant for: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, and Esaote, E. Naredo Grant/research support: UCB and MSD, Consultant for: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, and Esaote, M. Montoro: None declared, L. Carreño Perez: None declared DOI 10.1136/annrheumdis-2014-eular.3274

THU0474 A cross-sectional study into the effectiveness of the fibromyalgia rapid screening tool for detecting fm in patients with chronic arthritis undergoing full and tapered biological disease-modifying antirheumatic drug therapy

Background The determination of fibromylagia (FM) in patients presenting diffuse, chronic arthritis is fraught. The Fibromyalgia Rapid Screening Tool (FiRST) is a validated questionnaire with high sensitivity and moderate specificity shown to be able to identify up to 89% of FM cases, even when accompanied by anxiety, depression or functional disability. Decisions to embark upon a course of full or tapered biological disease-modifying antirheumatic drugs (bDMARD) are influenced in part by patient self-assessment scores as well as concomitant pathologies. Objectives To evaluate the prevalence of FM using the FiRST questionnaire in bDMARD-treated chronic arthritis patients. Methods This cross-sectional study included 325 patients [178 (54,8%) females and 147 (45,2%) males] diagnosed with chronic arthritis and treated with bDMARD. Patients were consecutively recruited from the Biological Therapy Unit from January to March 2015 all having undergone full or tapered bDMARD for at least 1 year. Dosage tapering had been applied to patients considered to be in remission. All patients self-completed the FiRST questionnaire with a score>5/6 considered positive. Clinical assessment was carried out by one specialist only. Demographic, clinical and laboratory variables were recorded with pathology-specific indices used to assess disease status, i.e.DAS28-ESR, DAS28-CRP, SDAI, CDAI, BASDAI, BASFI, ASDAS-CRP. Patient pathologies were classified as peripheral arthritis (PerAR: RA, PsA, PerSpA) or axial spondyloarthropathy type (AxSpA). Results A total of 68/325 (21%) patients scored >5/6 in the FiRST. Disease duration and previous bDMARD usage were not significant regarding scores <5/6. In the PerAR vs. AxSpA group, we observed that 19% (n=43) and 35% (n=25) scored FiRST>5/6, respectively (p=NS). Fifteen per cent of patients with tapered bDMARD registered scores >5/6 against 85% of patients in full bDMARD dosage (p=0.001). There were a higher number of remission patients in the PerAR group as defined under DAS28-ESR, SDAI and CDAI [(96%, 94% and 94%) (p=0.01, p=0.04, p=0.032), respectively]. Association was found in the PerAR subgroups between tapered bDMARD and remission in RA patients only, as defined under DAS28-VSG, SDAI and CDAI (p=0.026, p=0.04, p=0.043, respectively). In the AxSpA tapered bDMARD subset, 86% of patients were considered to be in clinical remission as set out under BASDAI (p=0.019). Conclusions No difference was observed between the PerAR and AxSpA groups for FiRST>5/6. Fewer patients undergoing tapered bDMARD dosage recorded FiRST scores >5/6. Therefore, early identification of chronic arthritic patients presenting FiRST>5/6 may prove to be an important step in furthering understanding of clinical activity in diffuse arthritis as well as offering improved diagnostic and therapeutic outcomes to bDMARD-treated patients with possible concomitant FM. Disclosure of Interest None declared