Potential efficacy of T and B lymphocyte-targeted therapies on articular involvement of patients with rheumatoid arthritis and systemic sclerosis overlap syndrome. Results from a 2-centre series of 22 cases.

OBJECTIVES: To analyse in routine practice the efficacy of targeted therapies on joint involvement of patients with rheumatoid arthritis/systemic sclerosis (RA/SSc) overlap syndrome. METHODS: This was a retrospective analysis of medical records of two academic centres over a 10-year period. Joint response to targeted therapies was measured according to EULAR criteria based on Disease Activity Score (DAS)-28. In addition, changes in CRP level and glucocorticoid consumption were recorded. RESULTS: Nineteen patients were included. Methotrexate (n=11) and hydroxychloroquine (n=4) were the most used first-line treatments. Targeted therapies were frequently used (n=14). Tocilizumab was the most selected therapy (n=8), then rituximab (n=5), abatacept and anti-tumour necrosis factor (n=4). Twenty-one treatment sequences were assessed, including 18 with EULAR response criteria. Responses were "good" or "moderate" in 100% (4/4) of patients treated with abatacept, 80% (4/5) with rituximab, 40% (2/5) with tocilizumab, and 25% (1/4) with anti-TNF. T and B lymphocyte-targeted therapies (abatacept, rituximab) resulted more frequently in a "good" or "moderate" response compared to cytokine inhibitors (tocilizumab, etanercept, infliximab) with a significant decrease in DAS-28 at 6 months (-1.75; p=0.016) and a trend to a lower consumption of glucocorticoids. CCONCLUSIONS: In patients with RA/SSc overlap syndrome refractory to conventional synthetic-DMARDs, T and B lymphocyte-targeted therapies seem to be a promising therapeutic option to control joint activity.

Can efficacy and safety data from clinical trials of rituximab in RA be extrapolated? Insights from 1984 patients from the AIR-PR Registry.

OBJECTIVES: To investigate whether the efficacy and safety data from drug-registration trials can be extrapolated to real-life RA patients receiving RTX. METHODS: The AIR-PR registry is a French multicentre, prospective cohort of RA patients treated with RTX in a real-life setting. We compared treatment responses at 12 months and serious AEs between eligible and non-eligible patients, by retrieving the eligibility criteria of the three rituximab-registration trials. We determined critical eligibility criteria and modelled the benefit-risk ratio according to the number of fulfilled critical eligibility criteria. RESULTS: Among 1984 RA patients, only 9-12% fulfilled all eligibility criteria. Non-eligible patients had less EULAR response at 12 months (40.3% vs 46.9%, p= 0.044). Critical inclusion criteria included SJC ≥ 4, TJC ≥ 4, CRP ≥ 15 mg/l, and RF positivity. Critical exclusion criteria were age >80 years, RA-associated systemic diseases, ACR functional class IV, other DMARD than methotrexate, and prednisone > 10 mg/day. Only 20.8% fulfilled those critical eligibility criteria. During the first year, serious AEs occurred for 182 (9.2%) patients, (70.3% serious infections) and patients with ≥1 critical exclusion criterion were at higher risk (HR 3.03; 95%CI 2.25-4.06; for ≥ 3 criteria vs 0). The incremental risk-benefit ratio decreased with the number of unmet critical inclusion criteria and of fulfilled exclusion criteria. CONCLUSION: Few real-life RA patients were eligible for the drug-registration trials. Non-eligible patients had lower chance of response, and higher risk of serious AEs. Efficacy and safety data obtained from those trials may not be generalizable to RA patients receiving RTX in real-world clinical practice.

Bone, cognitive, and anthropometric profiles and their relation to fracture sites in fallers: a cross-sectional study.

Risk factors involved in the different osteoporotic fracture locations are not well-known. The results of this study suggest that there is not one typical profile characterising a particular fracture site but that the occurrence of a fracture may result from the combination of different bone, cognitive, and anthropometrics characteristics. PURPOSE: Risk factors involved in the different osteoporotic fracture locations are not well-known. The aim of this study was to identify the differences in bone, cognitive, and anthropometric characteristics between different fracture sites, and to determine whether the site of a fall-related fracture is related to a specific profile. METHODS: One hundred six women aged 55 years and older with a recent fall-related fracture of the hip (n = 30), humerus (n = 28), wrist (n = 32), or ankle (n = 16) were included. Bone, cognitive, and anthropometric characteristics were first compared among the four fracture site groups. Then, a principal component analysis (PCA) was performed and a comparison was made between the four profiles identified by the first two PCA components. RESULTS: The four fracture site groups differed significantly in their education level, bone mineral density (BMD), body mass index (BMI), fear of falling, and number of errors in the Trail Making Test B, an executive function test. Each of the four fracture sites was found in each four PCA profiles, albeit with a different distribution. The profiles differed mainly by bone, cognitive, and anthropometric characteristics, but also by fear of falling. CONCLUSIONS: The fall-related fracture sites differ significantly in anthropometric and bone parameters, in fear of falling and in cognitive abilities. There is not one typical bone, cognitive, and anthropometric profile characterising a particular fall-related site, but rather several possible profiles for a given site. This suggests that the fracture site depends on a combination of several characteristics of the patient.

Clinical and ultrasonographic evaluation of the window of opportunity for retreatment with rituximab in rheumatoid arthritis patients from a multicentre real-life study.

OBJECTIVES: To determine a potential window of opportunity for retreatment with rituximab in patients with rheumatoid arthritis (RA) from a multicentre longitudinal real-life study based on tight monitoring with ultrasonography (US). METHODS: Thirty RA patients treated with rituximab were included. US parameters were collected at each time (8 visits) of the 18-month follow-up, notably the global score of power Doppler (PD) activity. Clinical relapse was defined as a DAS28 ESR of >3.2 after 6 months in responders while US relapse was defined as an increase of ≥20% of the global score of PD activity. The decision of retreatment was based exclusively on clinical findings. RESULTS: A total of 29 patients were analysed (mean (SD) age: 57.2 (12.2) years; female gender: 66%). The mean (SD) PD score decreased from 8.8 (5.2) at baseline to 4.9 (4.3) at 6 months (p <0.0001). A clinical response was observed at Month 4 or Month 6 for 93% of patients. A total of 19 patients had a first clinical relapse (with or without US relapse) after Month 6 (18 of them were retreated with rituximab). Among 10 patients without clinical relapse, 3 had US relapse (only one was retreated) and 7 had no US relapse (but 4 were retreated). CONCLUSIONS: This study highlights a great heterogeneity in terms of sequence of clinical relapse, US relapse and retreatment in RA patients receiving rituximab. Therefore, US monitoring does not seem to be relevant to determine the best time for retreatment with rituximab.

Clinical significance of a self-reported familial occurrence of rheumatoid arthritis among patients with recent-onset arthritis: data from the ESPOIR cohort.

OBJECTIVES: To assess, in patients with recent-onset arthritis, whether a self-reported familial occurrence of rheumatoid arthritis (RA) is associated with a clinical presentation of the disease, final diagnosis, long-term outcome and treatment decisions. METHODS: The study was conducted from data of patients included between 2002 and 2005 in the early arthritis ESPOIR cohort. Patients were recruited on the basis of having at least two swollen joints for >6 weeks and <6 months, no other diagnosis than RA and no previous exposure to glucocorticoids or disease-modifying antirheumatic drugs (DMARDs). Patients were stratified into two groups according to the presence of a self-reported familial occurrence of RA at baseline. Data concerning final diagnosis (2-year visit), long-term outcome (5-year visit) and therapeutic decisions were compared between the 2 groups of patients, using logistic and Cox regression models. RESULTS: At baseline, 115 patients (14.1%) reported a familial occurrence of RA and showed, as compared with the remaining participants, higher prevalence of extra articular manifestations (EAMs) (51.8% vs. 39.6%, p=0.01) and severe EAMs (7.9% vs. 3.1%, p 0.01). Both unadjusted (hazard ratio, 1.57; 95% CI, 1.1-2.21; p = 0.01) and adjusted analysis (hazard ratio, 1.51; 95% CI, 1.06-2.15; p=0.02) identified a higher probability for the initiation of a targeted DMARD over time among patients with a self-reported familial occurrence of RA. CONCLUSIONS: In the specific context of early arthritis, a self-reported familial occurrence of RA is associated with the future decision to initiate a targeted DMARD.

Potential Benefit of Rituximab in Rhupus Patients From a Single-Center: A Series of 16 Cases.

BACKGROUND: Rhupus syndrome is better characterized, but uncertainties remain, and therapeutic management must be defined. The objective was to analyze therapeutic procedures with a focus on biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: This 10-year medical records review was based on diagnosis codes (rheumatoid arthritis [RA] and systemic lupus erythematosus [SLE]) and biological data (anti-CCP testing, anti-dsDNA, and anti-RNP antibodies). Patients fulfilling 2010 ACR/EULAR and 2012 SLICC and/or 2019 ACR/EULAR classification criteria for RA and SLE, respectively, were included. RESULTS: Sixteen patients were identified. Rheumatoid arthritis most often preceded rhupus, with predominant articular pattern; 11 of them had erosive arthropathy. Skin involvement was the most frequent associated manifestation (n = 12). Serious events were reported, including active glomerulonephritis (n = 3), ischemic stroke (n = 1), and myocardial infarction (n = 1). Immunological profiles showed positivity for antinuclear (n = 16), anti-dsDNA (n = 9), and anti-CCP (n = 9). Ten patients required bDMARDs. All types of RA-approved bDMARDs were used. Abatacept was considered effective in 3 of the 4 patients, with 1 primary failure, 1 secondary escape, and 2 therapeutic maintenances, whereas primary or secondary failure was observed under tocilizimub and TNF-blocking agents. Rituximab was the most prescribed (n = 9) and the most effective with a sustained response in 6 patients. CONCLUSIONS: In rhupus refractory to conventional treatment, T or B lymphocytes targeted therapies, and particularly rituximab, seem to be a relevant therapeutic option unlike anticytokine biologics.

Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial.

OBJECTIVES: No immunomodulatory drug has been approved for primary Sjögren's syndrome, a systemic autoimmune disease affecting 0.1% of the population. To demonstrate the efficacy of targeting interleukin 6 receptor in patients with Sjögren's syndrome-related systemic complications. METHODS: Multicentre double-blind randomised placebo-controlled trial between 24 July 2013 and 16 July 2018, with a follow-up of 44 weeks, involving 17 referral centres. Inclusion criteria were primary Sjögren's syndrome according to American European Consensus Group criteria and score ≥5 for the EULAR Sjögren's Syndrome Disease activity Index (ESSDAI, score of systemic complications). Patients were randomised to receive either 6 monthly infusions of tocilizumab or placebo. The primary endpoint was response to treatment at week 24. Response to treatment was defined by the combination of (1) a decrease of at least 3 points in the ESSDAI, (2) no occurrence of moderate or severe activity in any new domain of the ESSDAI and (3) lack of worsening in physician's global assessment on a Visual Numeric Scale ≥1/10, all as compared with enrolment. RESULTS: 110 patients were randomised, 55 patients to tocilizumab (mean (SD) age: 50.9 (12.4) years; women: 98.2%) and 55 patients to placebo (54.8 (10.7) years; 90.9%). At 24 weeks, the proportion of patients meeting the primary endpoint was 52.7% (29/55) in the tocilizumab group and 63.6% (35/55) in the placebo group, for a difference of -11.4% (95% credible interval -30.6 to 9.0) (Pr[Toc >Pla]=0.14). CONCLUSION: Among patients with primary Sjögren's syndrome, the use of tocilizumab did not improve systemic involvement and symptoms over 24 weeks of treatment compared with placebo. TRIAL REGISTRATION NUMBER: NCT01782235.

Cardiac involvement in adult-onset Still's disease: Manifestations, treatments and outcomes in a retrospective study of 28 patients.

OBJECTIVE: Adult-onset Still's disease (AOSD) is a rare inflammatory disease that may be life-threatening if complicated by cardiac problems. We performed a retrospective multicenter study to describe the manifestations, treatments and outcomes of cardiac involvement in AOSD. METHODS: We reviewed the medical databases of eight centers. All AOSD patients identified as fulfilling Yamagushi's or Fautrel's criteria were included in the study. Cardiac involvement, clinical manifestations, laboratory features, the course of the disease and treatments were evaluated. RESULTS: We included 96 AOSD patients in this study: 28 (29%) had documented cardiac involvement (AOSD + C group) and 68 (71%) had no cardiac involvement (control group). Cardiac complications were observed at diagnosis in 89% of cases. It were pericarditis (n = 17), tamponade (n = 5), myocarditis (n = 5) and non-infectious endocarditis (n = 1). Levels of leukocytes, neutrophils and C-reactive protein were significantly higher (p = 0.02, p = 0.02 and p = 0.002, respectively in the AOSD + C group than in the control group. Admission to intensive care, and the use of biotherapy were more frequent during follow-up in the AOSD + C group than the control group (p = 0.0001 and p = 0.03 respectively). Cardiac involvement was associated with refractory form in multivariate analyzed (p = 0.01). Corticosteroids were effective with or without methotrexate in 71% of patients but not in severe involvement as myocarditis or tamponade. CONCLUSION: Cardiac complications are frequent, inaugural, can be life-threatening and predictive of a refractory course in patients with AOSD. Systematic cardiac screening should be proposed at diagnosis and biotherapy early use should be considered especially in myocarditis.

Cut-off value to identify a flare using the Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire: analysis of the TOSCA study.

OBJECTIVE: The Flare Assessment in RA (FLARE-RA) self-administered questionnaire aims to identify patients who had flare in the interval between two consultations. This study aimed to establish a threshold for FLARE-RA score to identify RA flare. METHODS: The Tocilizumab SubCutAneous study evaluated the efficacy and safety of s.c. tocilizumab (TCZ) to patients with active RA. Disease activity was assessed with the DAS28ESR at baseline and at week 2 (W2), W4, W12 and W24. The FLARE-RA questionnaire was administered at W12 and W24. Patient satisfaction, assessed at baseline and W24 with the Patient Acceptable Symptom State (PASS), was used as a surrogate marker of no flare. A correlation was sought between the FLARE-RA score at W12 and W24 and the area under the receiver operating characteristic (ROC) curve (AUC) for monthly DAS28ESR. The optimal FLARE-RA cut-off below which patient satisfaction reached the PASS was explored with an ROC curve. RESULTS: A total of 139 patients were included (mean age 57.3 ± 13.8 years, 74.1% women, mean RA duration 10.8 ± 9.2 years, mean DAS28ESR 5.8 ± 1.1). The correlation between the FLARE-RA score and DAS28ESR AUC was moderate at all times: ρ = 0.41 at W12 (P < 0.0001) and 0.51 at W24 (P < 0.0001). The optimal cut-off for the FLARE-RA score to identify absence of flare (i.e. an acceptable situation based on the PASS) was 2.3 with an AUC of 0.81. CONCLUSION: FLARE-RA and DAS28ESR assessment differ; we propose a FLARE-RA cut-off of 2.3, below which the situation (i.e. without flare) is acceptable for patients.

Refining myositis associated with primary Sjögren's syndrome: data from the prospective cohort ASSESS.

OBJECTIVES: To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). METHODS: The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months' follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. RESULTS: Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested 'pure' pSS myositis. Steroids plus MTX was then efficient in achieving remission. CONCLUSIONS: Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.

Current favourable 10-year outcome of patients with early rheumatoid arthritis: data from the ESPOIR cohort.

OBJECTIVE: To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. METHODS: From 2003 to 2005, 813 patients were included if they had early arthritis (<6 months) with a high probability of RA and had never been prescribed DMARDs. Multivariate analysis was used to evaluate predictors of outcome. RESULTS: In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. CONCLUSIONS: We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.

Microbiological diagnosis of suspected vertebral osteomyelitis with a focus on the yield of percutaneous needle biopsy: a 10-year cohort study.

This study aims to evaluate in patients hospitalized for vertebral osteomyelitis (VO) the effectiveness of bacteriological diagnosis and the yield of percutaneous needle biopsy (PNB) and to identify factors associated with the result of PNB. This retrospective, two-centre study was conducted between 2000 and 2009. Data on patients with VO were retrieved from the diagnosis database and confirmed by checking medical records. A total of 300 patients with VO were identified; 31 received antibiotics without bacteriological diagnosis, and 269 patients with spondylodiscitis imaging were included. Eighty-three (30.9%) and 18 (6.7%) infections were documented by blood cultures and by bacteriological samples other than PNB, respectively; 168 patients with no bacteriological diagnosis had PNB. Of these, 92 (54.8%) were positive and identified the pathogen and 76 (45.2%) were negative. The most common bacteria were Staphylococcus aureus (34.3%), Streptococcus spp. (20.6%) and coagulase-negative staphylococcus (14.8%). After multivariate analysis, the only factor associated with negative PNB was previous antibiotic intake (OR: 2.31 [1.07-5.00]). When VO was suspected on imaging, bacteriological investigation identified the microorganism in 209/300 (70%) of the cases. The yield of PNB was 54.8%. The only predictor of PNB negativity was previous antibiotic intake. Therefore, we believe that a second PNB should be done after a sufficient delay withdrawal of antibiotics if the first sample was negative. The study was retrospectively registered by the local ethics committee (N°E2019-61).

Is early-onset primary Sjögren's syndrome a worse prognosis form of the disease?

OBJECTIVES: Onset of primary SS is usually between 40 and 60 years of age, with severe systemic complications in 15% of cases. We sought to determine whether early-onset disease is related to a specific phenotype and if it is predictive of a poor outcome. METHODS: Biological and clinical data from 393 patients recruited in the ASSESS cohort, a French multicentre prospective cohort, were compared according to age at diagnosis. RESULTS: Fifty-five patients had early-onset disease, defined as age ⩽35 years at diagnosis, and presented a significantly higher frequency of salivary gland enlargement (47.2% vs 33.3%, P = 0.045), adenopathy (25.5% vs 11.8%, P = 0.006), purpura (23.6% vs 9.2%, P = 0.002) and renal involvement (16.4% vs 4.4%, P = 0.003). They had a higher frequency of hypergammaglobulinaemia (60.8% vs 26.6%, P < 0.001), RF positivity (41.5% vs 20.2%, P < 0.001), low C3 level (18.9% vs 9.1%, P = 0.032), low C4 level (54.7% vs 40.2%, P = 0.048) and autoantibodies [84.6% with anti-SSA vs 54.4% (P < 0.001) and 57.7% with anti-SSB vs 29.7% (P < 0.001)]. The change in ESSDAI scores between baseline and the 5-year follow-up was significantly different (P = 0.005) with a trend for worsening in the early-onset group (0.72, P = 0.27) and a significant improvement in the later onset group (-1.27, P < 0.0001). CONCLUSION: Early-onset primary SS is associated with a specific phenotype defined by clinical and biological features known to be predictive factors of severe systemic disease. Interestingly, we showed a different evolution of the ESSDAI score depending on the age at disease onset, patients with early-onset disease tending to worsen over time.

Risk factors of serious infections in patients with rheumatoid arthritis treated with tocilizumab in the French Registry REGATE.

Objectives: Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA. Methods: A total of 1491 RA patients included in the French REGistry-RoAcTEmra were analysed to calculate the incidence rate of first serious infections rate after initiation of tocilizumab. To identify independent factors associated with serious infections, a Cox model was performed. Results: Among the 1491 patients, average age 56.6 (13.6) years, 125 serious infections occurred in 122 patients (incidence rate of serious infection: 4.7/100 patient-years). Univariate analysis identified initial ACPA positivity as the only factor associated with a lower risk of serious infection [hazard ratio (HR) = 0.56, 95% CI: 0.36, 0.88]. Other factors significantly associated with a higher risk of serious infections were DAS28, concomitant Leflunomide (LEF) treatment, and absolute neutrophil count (ANC) at baseline. Initial ANC above 5.0 × 109/l (HR = 1.94, 95% CI: 1.32, 2.85; P < 0.001), negative ACPA (HR = 1.79, 95% CI: 1.15, 2.78; P = 0.012) at baseline and concomitant LEF treatment (LEF alone vs no treatment, HR = 2.18, 95% CI: 1.22, 3.88; P = 0.009) remained significantly associated with first serious infections in multivariate analysis after imputation for missing data. Conclusion: The rate of first serious infections in current practice is similar to that reported in clinical trials. High ANC (above 5.0 × 109 at baseline), negative ACPA and concomitant therapy with LEF are predictive factors of serious infection, requiring in this case a tighter surveillance.

Safety of surgery in patients with rheumatoid arthritis treated by abatacept: data from the French Orencia in Rheumatoid Arthritis Registry.

Objective: To investigate the frequency and risk factors of postoperative complications in RA patients treated with abatacept (ABA). Methods: The Orencia RA registry recruited 1012 patients receiving ABA for RA in routine care. Data from patients treated with ABA who underwent surgery were reviewed to describe the frequency of postoperative complications. Characteristics of patients and surgeries with and without complications were compared to identify factors associated with complications. Results: We identified 205 (20.3%) patients who underwent 263 surgeries, including 176 (66.9%) orthopaedic surgeries. Nineteen (7.2%) surgeries, in 19 patients (9.3%), entailed complications, including 7 delayed wound healing (2.7% of surgeries) and 6 surgical site infections (2.3% of surgeries). The median time between the last infusion of ABA and surgery was 5.9 weeks (range: 0.3-12.0 weeks), with no significant difference between patients with and without complications. The median corticosteroids daily dosage was higher in the group with complications [10.0 (6.25-15.0) vs 6.0 (5.0-10.0) mg/day, P = 0.042]. In multivariate analysis, only the duration of ABA treatment was significantly associated with postoperative complications [adjusted odds ratio (aOR) = 0.94 (95% CI: 0.89, 0.99) for each month of treatment], as were orthopaedic surgeries compared with other kinds of surgery [aOR = 4.45 (95% CI: 1.01, 20.2)]. Conclusion: In RA patients treated with ABA, the rate of surgical complications was low: 7.2% and higher in case of orthopaedic procedure and a more recent initiation of ABA. The median time between surgery and the last infusion of ABA was short and did not influence the rate of postoperative complications.

Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study.

OBJECTIVES: To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). METHODS: In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology-European League Against Rheumatism (OMERACT-EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT-EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2-5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. RESULTS: Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2-5): -0.7 (95% CIs -1.2 to -0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. CONCLUSIONS: In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. TRIAL REGISTRATION NUMBER: NCT00767325.

Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjögren's syndrome.

OBJECTIVES: To determine whether B-cell markers (blood and minor salivary gland [SG] B-cell depletion [BCD], autoantibodies, B-cell-activating factor [BAFF]) are associated with clinical response to rituximab in patients with primary Sjögren's syndrome (pSS). METHODS: 45 patients with pSS were included: in group I, 14 received low-dose rituximab (two 375-mg/m(2) infusions) in an open-labelled study; in group II, 17 received full-dose rituximab (two 1000-mg infusions) and 14 received a placebo in a randomized, controlled study. The proportion of SG B cells was assessed using pixel-based software analyses of digitized double-immunostained (CD3/CD20) whole SGs. Response was defined at week-24 according to the Sjögren's Syndrome Responder Index (SSRI)-30. RESULTS: Response rate was 50% in both groups of rituximab-treated patients. Duration of blood BCD was similar in both groups despite the difference in rituximab dosage, and was highly correlated with residual serum-rituximab levels at week-16. SG B-cell dynamics mirrored blood B-cell levels, with a drastic decrease in SG B-cells at week-12 (group I), but an increase in ∼ 50% of patients in group II by week-24, in whom blood B cells had already returned. Duration of BCD was not associated with the clinical response, but responders had lower baseline proportions of SG B cells. Baseline serum BAFF level was correlated with the proportion of SG B-cells and other B-cell-activation markers, and was associated with the clinical response with higher levels in non-responders. CONCLUSIONS: In pSS, half of the patients display an intense BAFF-driven B-cell activation and do not respond to a single course of rituximab.