Long-Term Retention Rate of Golimumab in Patients With Rheumatoid Arthritis, Psoriatic Arthritis, and Spondyloarthritis in a Real-Life Setting.

METHODS: We conducted a single-center, medical records review study of all patients with RA, PsA, and SpA on GLM treatment attending a large rheumatology department from 2010 to 2017. Times from start to end of GLM treatment were collected, as well as sociodemographic, clinical, and safety variables. Golimumab retention rate was estimated by the Kaplan-Meier method, and comparison across diseases was analyzed with the Mantel-Haenszel statistic (log-rank test). Cox proportional hazards regression models were used to identify factors associated with GLM discontinuation. RESULTS: In the study period, a total of 212 patients (61 RA, 48 PsA, 103 SpA) were prescribed GLM. Retention rates were 72% in the first year, 61% in the second, 56% in the third, and 38% at 5 years. Differences were statistically significant across diseases (median times to GLM discontinuation were 50.2, 46.0, and 38.7 months for RA, SpA, and PsA, respectively) and according to the number of previous biologic therapies (55.2 months in biologic-naive patients vs 14.0 months in patients with ≥2 previous biologics; p < 0.001). The use of concomitant conventional synthetic disease-modifying antirheumatic drugs was associated with a lower probability of discontinuation (hazards ratio [HR], 0.57; 95% confidence interval [CI], 0.33-0.97). Female sex (HR, 1.84; 95% CI, 1.07-3.17) and having used 2 biologics before GLM (HR, 2.99; 95% CI, 1.76-5.06) were associated with increased discontinuation rates. Twenty-three patients (10.9%) had at least 1 serious adverse event. CONCLUSIONS: In a real-life setting, GLM shows appropriate long-term safety-effectiveness ratio.

Clinical Characteristics of Juvenile Idiopathic Inflammatory Myopathy and Comparison With Adult Patients: Analysis From a Multicentric Cohort in Spain.

METHODS: This study reviewed the medical records of patients from the REMICAM cohort, a multicentric longitudinal study carried out in patients with IIM, followed up between 1980 and 2014 in 12 hospitals in Madrid, Spain. Patients with definite or probable JPM, JDM, adult DM, and adult PM according to the modified Bohan and Peter criteria were selected. We compared the characteristics between JDM and JPM, and between JIIM and adult IIM. RESULTS: Eighty-six juvenile patients (75 JDMs and 11 JPMs) and 283 adult patients (133 DMs and 150 PMs) were included. Compared with patients with JDM, patients with JPM were older at diagnosis, had more fever and arthritis, and were less frequently treated with disease-modifying antirheumatic drugs (these differences were not statistically significant). Compared with patients with adult DM, those with JDM presented more frequently with calcinosis (33.8% vs 6.9%, p < 0.0001) and had less severe infections (4.3% vs 23.4%, p < 0.0001), malignancies (1.3% vs 25.6%, p < 0.0001), and mortality (3.5% vs 33%, p < 0.0001). Patients with JDM were treated less frequently with azathioprine (10.8% vs 44.7%, p < 0.0001). CONCLUSIONS: Our findings confirm that JIIMs are a heterogeneous group of diseases with relevant differences compared with adult IIMs.

Performance of ultra-high-frequency ultrasound in the evaluation of skin involvement in systemic sclerosis: a preliminary report.

OBJECTIVE: High frequency ultrasound allows visualization of epidermis, dermis and hypodermis, precise measurement of skin thickness, as well as assessment of skin oedema, fibrosis and atrophy. The aim of this pilot cross-sectional observational study was to assess the performance and multiobserver variability of ultra-high-frequency (UHF) (50 MHz) ultrasound (US) in measuring skin thickness as well as the capacity of UHF-derived skin features to differentiate SSc patients from healthy controls. METHODS: Twenty-one SSc patients (16 limited and five diffuse SSc) and six healthy controls were enrolled. All subjects underwent US evaluation by three experts at three anatomical sites (forearm, hand and finger). Dermal thickness was measured and two rectangular regions of interest, one in dermis and one in hypodermis, were established for texture feature analysis. RESULTS: UHF-US allowed a precise identification and measurement of the thickness of the dermis. The dermal thickness in the finger was significantly higher in patients than in controls (P < 0.05), while in the forearm it was significantly lower in patients than in controls (P < 0.001). Interobserver variability for dermal thickness was good to excellent [forearm intraclass correlation coefficient (ICC) = 0.754; finger ICC = 0.699; hand ICC = 0.602]. Texture computed analysis of dermis and hypodermis was able to discriminate between SSc and healthy subjects (area under the curve >0.7). CONCLUSION: These preliminary data show that skin UHF-US allows a very detailed imaging of skin layers, a reliable measurement of dermal thickness, and a discriminative capacity between dermis and hypodermis texture features in SSc and healthy subjects.

Digestive involvement in primary Sjögren's syndrome: analysis from the Sjögrenser registry.

OBJECTIVES: Digestive involvement (DI) has been reported in 10-30% of primary Sjögren's syndrome (pSS) patients, and few studies have systematically analysed the prevalence of DI in pSS patients. The aim of this study was to describe DI prevalence in pSS patients from the Sjögrenser Study, and to analyse its clinical associations. METHODS: All patients included in the Sjögrenser study, a Spanish multicentre randomised cohort, containing demographic, clinical and histologic data, have been analysed retrospectively. Patients were classified according to the presence of DI (oesophageal, gastric, intestinal, hepatic and pancreatic), and we have performed DI clinical associations, descriptive statistics, Student t or χ2 test, and uni and multivariate logistic regression. RESULTS: From 437 included patients, 95% were women, with a median age of 58 years, 71 (16.2%) presented DI: 21 (29.5%) chronic atrophic gastritis, 12 (16.9%) oesophageal motility dysfunction, 3 (4.2%) lymphocytic colitis, 18 (25.3%) primary biliary cholangitis, 15 (21.1%) autoimmune hepatitis, 7 (9.8%) pancreatic involvement and 5 (7%) coeliac disease. Half of them developed DI at the same time or after pSS diagnosis. Patients with DI were significantly older at pSS diagnosis (p=0.032), more frequently women (p=0.009), presented more autoimmune hypothyroidism and C3 hypocomplementaemia (p=0.040), and were treated more frequently with glucocorticoids, immunosuppressant and biologic therapies. Patients with pancreatic involvement presented more central nervous system and renal involvement, Raynaud's phenomenon, lymphoma and C3/C4 hypocomplementaemia. CONCLUSIONS: DI is frequent in Sjögrenser patients, mainly in the form of autoimmune disorders, and seem to be associated with a more severe phenotype. Our results suggest that DI should be evaluated in pSS patients, especially those with more severe disease.

Prevalence and factors associated with osteoporosis and fragility fractures in patients with primary Sjögren syndrome.

This study aimed at determining socio-demographic and clinical factors of primary Sjögren syndrome (pSS) associated with osteoporosis (OP) and fragility fracture. SJOGRENSER is a cross-sectional study of patients with pSS, classified according to American European consensus criteria developed in 33 Spanish rheumatology departments. Epidemiological, clinical, serological and treatment data were collected and a descriptive analysis was conducted. Bivariate and multivariate analyses were performed using a binomial logistic regression to study the factors associated with OP and fragility fracture in pSS. 437 patients were included (95% women, with a median age of 58.6 years). 300 women were menopausal (76.4%). Prevalence of OP was 18.5% [in men (N = 21) this measured 19%]. A total of 37 fragility fractures were recorded. In the multivariate analysis, there was an association between OP and age: in the 51-64 age range (menopausal women), the OR measured 9.993 (95% CI 2301-43,399, p = 0.002); In the age > 64 years group, OR was 20.610 (4.679-90.774, p < 0.001); between OP and disease duration, OR was 1.046 (1.008-1085, p = 0.017); past treatment with corticosteroids, OR 2.548 (1.271-5.105, p = 0.008). Similarly, an association was found between fragility fractures and age: in the 51-64 age group, OR measured 5.068 (1.117-22,995, p = 0.035), age > 64 years, OR was 7.674 (1.675-35,151, p < 0.009); disease duration, OR 1.049 (CI 1.003-1097, p < 0.036) and the ESSDAI index, OR 1.080 (1.029-1134, p = 0.002). Patients with pSS can develop osteoporosis and fragility fractures over the course of the disease. Age, corticosteroids treatment and disease duration were associated with the development of OP. Disease duration and ESSDAI were associated with the development of fractures in patients with pSS.

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease.

PURPOSE: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.

An exploratory study to determine whether infliximab modifies levels of rheumatoid factor and antibodies to cyclic citrullinated peptides in rheumatoid arthritis patients.

OBJECTIVES: The aim of this study was to investigate the relationship between serum infliximab (IFX) levels and changes of RF and ACPA levels in patients with rheumatoid arthritis (RA). METHODS: Enzyme-linked immunosorbent assays (ELISA) [Promonitor® IFX R1 (version 2) (Progenika Biopharma, Spain)] were used to measure drug levels and antidrug-antibodies (ADAb) in IFX RA-treated patients (n=19). Disease activity was assessed using DAS28. IgM rheumatoid factor (RF) and IgM, IgA and IgG anti-cyclic citrullinated peptide (ACPA) were determined through ELISA. RESULTS: A significant decrease in RF (p=0.01), ACPA IgG (p=0.007), IgM (p=0.01) and IgA (p=0.03) was observed in patients presenting adequate levels of serum IFX. No significant changes to RF or ACPA were observed in patients with undetectable IFX. CONCLUSIONS: Data from this study support the hypothesis that the anti-TNF antagonist IFX downregulates autoantibody levels in RA patients when IFX levels are detectable. Larger-scale studies need to be performed to establish RF and ACPA presence as therapeutic response predictive factors.

Timing of onset affects arthritis presentation pattern in antisyntethase syndrome.

OBJECTIVES: To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). METHODS: The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). RESULTS: 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). CONCLUSIONS: In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.

Variability in the prescription of biological drugs in rheumatoid arthritis in Spain: a multilevel analysis.

To describe variability in the prescription of biologics (B-DMARDs) for patients with rheumatoid arthritis (RA) in hospitals in Spain, and to explore which characteristics of the patient, the doctor and the hospital are associated with this variability. Cross-sectional multicentric study in 46 rheumatology services of the National Health System. Medical records of 1188 randomly selected patients were reviewed. The association of each variable with B-DMARD prescription was analyzed using simple logistic regressions. Multilevel logistic regression models were created to analyze variability among centers. 36.8% of patients had received B-DMARD. The proportion of patients being treated with B-DMARDs varied between 3.6 and 71.4% depending on the center. Association of prescription of B-DMARD with patient age (OR = 0.958, 95% CI = 0.947-0.968, p < 0.001), longer disease duration (OR = 1.05, 95% CI = 1.032-1.069, p < 0.001), higher CRP levels (OR = 1.022, 95% CI = 1.003-1.042, p = 0.023), and higher number of hospitalizations (OR = 1.286, 95% CI = 1.145-1.446, p < 0.001) was observed. With regard to the center characteristics, the existence of telephone consultations (OR = 1.438, 95% CI = 1.037-1.994, p = 0.03) and the number of beds (OR = 1.045, 95% CI = 1.001-1.091, p = 0.044) were positively associated with prescription of B-DMARDs. Patient variables explained 34.04% of the variability among centers. By adjusting for patient and hospital characteristics, it went up to 83.71%. There is variability in the prescription of B-DMARDs for patients with RA among hospitals which is associated, to a greater extent, with the center characteristics. B-DMARDs prescription could be partly explained by other factors not covered by the current study including the provider's attitudes towards biologics and other hospital characteristics.

Identifying markers of sustained remission in rheumatoid arthritis patients on long-term tapered biological disease-modifying antirheumatic drugs.

To identify features associated with long-term persistent remission in rheumatoid arthritis (RA) patients on tapered biological disease-modifying antirheumatic drugs (bDMARD) (tap-bDMARD) therapy. We carried out a 40-month (m) extension follow-up study of 77 RA patients from a previous 12 m tap-bDMARD study. Disease activity was assessed at baseline and every 3 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy (SH) and synovial power Doppler signal (i.e., Doppler synovitis) was performed before starting the tap-bDMARD strategy by a rheumatologist blinded to clinical and laboratory data. At the 40 m mark, 44 (57.1%) patients failed the tap-bDMARD strategy, while 33 (42.9%) succeeded. Patients who presented a failed tap-bDMARD had significantly longer disease duration, a longer time from symptom onset to synthetic (s) DMARD start, longer duration of sDMARD treatment, a greater number of sDMARDs, and a higher baseline DAS28 and SDAI than patients with successful tap-bDMARD at 40 months. In logistic regression analysis, the presence of baseline Doppler synovitis, a DAS28 ≥ 2.2, and the presence of rheumatoid factor were identified as predictors of tap-bDMARD failure at 40 m. In those patients who succeed tap-bDMARD at 12 m, a smoking habit was significantly more frequently found in tap-bDMARD failures at 40 m. Our results showed that DAS28 and the presence of Doppler synovitis, RF and a smoking habit predicted long-term tap-bDMARD failure.

Juvenile- and adult-onset systemic lupus erythematosus: a comparative study in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

OBJECTIVES: We aimed to describe juvenile-onset systemic lupus erythematosus (jSLE) features and to establish its differences compared to adult-onset SLE (aSLE) from a large national database. METHODS: Data from patients (≥4 ACR criteria) included in Spanish Society of Rheumatology Lupus Registry (RELESSER) were analysed. Sociodemographic, clinical, serological, activity, treatment, cumulative damage, comorbidities and severity data were collected. Patients with disease onset <18 years were described and compared to those with disease onset ≥18 years. RESULTS: We reviewed 3,428 aSLE patients (89.6% women) and 484 jSLE patients (89.8% girls), 93% Caucasian (both groups). Mean age at diagnosis was 38.1±14 and 16.6±6.3 years (p<0.001) and mean age at the end of follow-up was 48.8±14.3 and 31.5±30 years (p<0.001), respectively. jSLE showed significantly more clinical (including lymphadenopathy, fever, malar rash, mucosal ulcers, pericarditis, pleuritis, Raynaud's phenomenon, lupus nephritis, recurrent nephritis, histologic nephritis changes, thrombocytopenia, haemolytic anaemia, thrombotic thrombocytopenic purpura, seizures, lupus headache and organic brain syndrome) and immunological (a-dsDNA and a-Sm antibodies, hypocomplementaemia) involvement than did aSLE, except for secondary Sjögren's syndrome, a-Ro antibodies, fibromyalgia and osteoporosis. jSLE also showed more SLE family history, longer diagnosis delay, higher SLEDAI and Katz scores, but lower Charlson scores than aSLE. Several specific domains were more frequently involved in SLICC/ACR DI in jSLE. jSLE patients more frequently underwent all SLE-related treatment and procedures, as well as dialysis and kidney transplantations. CONCLUSIONS: jSLE shares many clinical and serological features with aSLE. However, jSLE patients typically manifested more activity, severity, cumulative damage in certain areas, than their aSLE counterparts.

Mortality and prognostic factors in idiopathic inflammatory myositis: a retrospective analysis of a large multicenter cohort of Spain.

The present study was undertaken to assess mortality, causes of death, and associated prognostic factors in a large cohort of patients diagnosed with idiopathic inflammatory myositis (IIM) from Spain. A retrospective longitudinal study was carried out in 467 consecutive patients with IIM, identified from 12 medical centers. Patients were classified as primary polymyositis, primary dermatomyositis (DM), overlap myositis, cancer-associated myositis (CAM), and juvenile idiopathic inflammatory myopathies. A total of 113 deaths occurred (24%) after a median follow-up time of 9.7 years. In the overall cohort, the 2-, 5-, and 10-year survival probabilities were 91.9, 86.7, and 77%, respectively. Main causes of death were infections and cancer (24% each). Multivariate model revealed that CAM (HR = 24.06), OM (HR = 12.00), DM (HR = 7.26), higher age at diagnosis (HR = 1.02), severe infections (HR = 3.66), interstitial lung disease (HR = 1.61), and baseline elevation of acute phase reactants (HR = 3.03) were associated with a worse prognosis, while edema of the hands (HR = 0.39), female gender (HR = 0.39), and longer disease duration (HR = 0.73) were associated with a better prognosis. The standardized mortality ratio was 1.56 (95% CI 1.28-1.87) compared to the Spanish general population. Our findings indicate that IIM has a high long-term mortality, with an excess of mortality compared to the Spanish population. A more aggressive therapy may be required in IIM patients presenting with poor predictive factors.

Structural damage in rheumatoid arthritis: comparison between tendon damage evaluated by ultrasound and radiographic damage.

OBJECTIVE: To compare structural damage assessed by conventional radiography and tendon damage assessed by musculoskeletal US (MSUS) at wrist and ankle in RA patients. METHODS: We evaluated 72 consecutive patients [56 (77.8%) females] with RA. The MSUS evaluation consisted in a B-mode examination of bilateral extensor carpi ulnaris and tibialis posterior tendons. Tendon damage was defined and scored according to OMERACT. A total score for the tendon damage score (TDS) was calculated by summing the grades for each tendon. For the radiographic evaluations we used the van der Heijde score; a total radiographic score (RTS) was calculated by summing a bone erosion score (ERS) and a joint space narrowing score (JSNS). RESULTS: We evaluated 288 tendons. The mean (s.d.) of TDS was 2.3 (1.8). Fifty-four (75%) patients presented tendon damage of at least one tendon. From all evaluated tendons, 134 (46.5%) had no tendon damage, 146 (50.7%) had grade 1 and 8 (2.8%) had grade 2 tendon damage. The mean (s.d.) for RTS was 91.4 (97), for ERS was 47.3 (61.9) and for JSNS was 44.1 (37.2). We found a significant correlation between disease duration and both TDS and RTS (r = 0.413 and r = 0.560, respectively; P < 0.0001). We found a good significant correlation between TDS and all variables of radiographic structural damage (RTS, r = 0.65; ERS, r = 0.637; JSNS, r = 0.618; P < 0.001). CONCLUSION: The MSUS assessment of only four tendons can be an additional feasible method to assess structural damage in RA patients.

Relationship between damage clustering and mortality in systemic lupus erythematosus in early and late stages of the disease: cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry.

OBJECTIVES: To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. RESULTS: Three damage clusters were identified. Cluster 1 (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 100% in clusters 2 and 3, P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 (8.0% of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. CONCLUSION: In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.

To what extent is foot pain related to biomechanical changes and ultrasound-detected abnormalities in rheumatoid arthritis?

OBJECTIVES: To investigate the presence of biomechanical abnormalities and ultrasound (US)-detected inflammation and damage in low disease or remission status rheumatoid arthritis (RA) patients with foot complaints. METHODS: We recruited 136 subjects with foot complaints. Sixty-two were biologic disease-modifying antirheumatic drug-treated RA patients presenting Disease Activity Score-determined remission or low disease activity while the remaining 74 were gender matched controls without rheumatic or musculoskeletal disorders. Both groups underwent a comprehensive podiatric, biomechanical and B-mode and Doppler US assessment of the feet. RESULTS: Most RA patients and controls were female (77.4% and 83.8%, respectively). There was no statistical difference in the proportion of obese subjects in either group (p=0.792). Inappropriate shoes were used by 50.0% of RA patients and 33.8% of controls (p=0.080). Talalgia, particularly heel pain, was more frequent in the control group, with associated talalgia and metatarsalgia being more prevalent in the RA group (p<0.05). The RA patient group was also more likely to present greater foot deformity, more limited joint movement and biomechanical abnormalities than the controls (p<0.05). US inflammatory and structural changes were significantly more frequent in RA patients than in controls (p<0.05). US structural involvement was significantly associated with limited joint mobility and pathologic biomechanical tests only in RA patients (p<0.05). CONCLUSIONS: RA foot complaints seemed to be linked to US-detected RA involvement and biomechanical abnormalities. Podiatric and US assessments can be useful to help the clinician to optimise the management of RA patients in remission/low disease activity with foot complaints.

The feet in systemic lupus erythematosus; are we underestimating their involvement and functional impact?

OBJECTIVES: To evaluate biomechanical and ultrasound (US) abnormalities in SLE patients as compared with controls and to assess the relationship between these abnormalities and SLE activity. METHODS: Fifty-four consecutive female patients with SLE with and without foot pain and 60 female controls (30 with foot pain and 30 without foot pain) were recruited. SLE activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). SLE patients and controls blindly underwent a comprehensive podiatric, biomechanical and US evaluation of the feet. US assessment included detection of B-mode synovitis, tenosynovitis, enthesopathy, bone changes and synovial, tenosynovial and entheseal power Doppler (PD) signal. RESULTS: Thirty-one (57.4%) SLE patients had bilateral foot pain and 5 (9.3%) had unilateral foot pain. Metatarsalgia was the most common location for pain but without significant difference between groups (p=0.284). Toe joint deformities were significantly more common in SLE feet as compared with control feet (p<0.0005). SLE feet showed significantly more biomechanical abnormalities than control feet (p<0.05). B-mode synovitis in the tibiotalar joint was strongly associated with having SLE (p<0.0005) and the presence of synovial PD signal in the MTP joints was found only in painful feet of SLE patients. SLEDAI was significantly higher in patients with foot pain than in those with painless feet (p=0.008). However, SLEDAI did not discriminate between patients with and without biomechanical or US abnormalities. CONCLUSIONS: SLE patients showed more biomechanical and US abnormalities in the feet than controls, which were not captured by standardised assessment of the disease activity.

Ultrasound-detected joint inflammation and B cell count: related variables for rituximab-treated RA patients?

This cross-sectional observational study aimed to explore the relationship between B cell count and ultrasound (US)-detected synovitis, in patients with rheumatoid arthritis treated with rituximab. Thirty-seven consecutive RA patients treated with RTX were recruited for the study. The patients underwent clinical [i.e., Disease Activity Score 28 joints (DAS28)], laboratory, and US assessment of 12 joints. Each joint was semiquantitatively (0-3) scored on B-mode and power Doppler mode. The scores were summed, and a global index was created for BM (BMS) and PD scores (PDI) synovitis. BM subclinical synovitis was evident in all patients, with PD synovial signal detected in 16 patients (43.2 %). No correlation was found between DAS28 and US scores. B cells were detected in 27 (72.9 %) patients, but there was no association in the mean B cell count and disease activity as measured by DAS28 (DAS28 < 2.6 = 34.53, DAS28 > 2.6 = 49.45, p = 0.52) and PDI score (PDI < 1 = 49.48, PDI > 1 = 35.44, p = 0.54). There was no correlation between the B cell count and DAS28, BMS, and PDI (r = 0.020, p = 0.907; r = -0.151, p = 0.371; r = -0.099, p = 0.558, respectively). In RTX-treated RA patients, no relationship could be established between US-detected synovitis and peripheral blood B cell count.

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.

Comparison of two ELISA versions for infliximab serum levels in patients diagnosed with ankylosing spondylitis.

There are various immunosorbent assays which can be used to determine infliximab (IFX) levels. Results vary between assays complicating reliability in everyday clinical practice. The aim of this study was to determine whether quantitative or qualitative assay data prove more accurate in the assessment of infliximab levels in AS patients. We analyzed 40 serum samples, taken prior to infusion, from AS patients who had been undergoing IFX therapy as a first-line of biological treatment for more than a year. IFX levels and IFX-anti-drug antibodies (ADA) were measured using two different ELISA assays [Promonitor IFX R1 and R2 (version 1), Promonitor IFX and anti-IFX (version 2) (Progenika Biopharma, Spain)] strictly following the manufacturer's guidelines. Cohen's unweighted kappa and the intraclass correlation coefficient determined qualitative and quantitative agreement for serum levels in version 1 and version 2. Bland-Altman plots were drawn to compare both assays. The comparison of data measuring IFX levels for version 1 and version 2 resulted in questionable quantitative agreement (ICC 0.659; 95% CI 0.317-0.830) and moderate qualitative agreement (κ 0.607; 95% CI 0.387-0.879) owing to systematically higher values in version 2 than version 1. Version 2 consistently detected higher levels of infliximab, particularly when analyzed in a quantitative context. Further research is needed to synchronize cutoff levels between essays and diseases so therapeutic drug ranges can be established.

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.