Predictive factors of effective tibial nerve release in tarsal tunnel syndrome.

BACKGROUND: Factors that may affect surgical decompression results in tarsal tunnel syndrome are not known. METHODS: A retrospective single-center study included patients who had undergone surgical tibial nerve release. The effectiveness of decompression was evaluated according to whether the patient would or would not be willing to undergo another surgical procedure in similar preoperative circumstances. RESULTS: The patients stated for 43 feet (51%) that they would agree to a further procedure in similar circumstances. Six feet with space-occupying lesions on imaging had improved results, but neurolysis failed in 9 feet with bone-nerve contact. Neurolysis was significantly less effective when marked hindfoot valgus (p = 0.034), varus (p = 0.014), or fasciitis (p = 0.019) were present. CONCLUSIONS: If imaging reveals a compressive space-occupying lesion, surgery has a good prognosis. In feet with static hindfoot disorders or plantar fasciitis, conservative treatment must be optimized. Bone-nerve contact should systematically be sought.

Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus.

Studies have suggested involvement of interleukin 17 (IL-17) in autoimmune diseases, although its effect on B cell biology has not been clearly established. Here we demonstrate that IL-17 alone or in combination with B cell-activating factor controlled the survival and proliferation of human B cells and their differentiation into immunoglobulin-secreting cells. This effect was mediated mainly through the nuclear factor-kappaB-regulated transcription factor Twist-1. In support of the relevance of our observations and the potential involvement of IL-17 in B cell biology, we found that the serum of patients with systemic lupus erythematosus had higher concentrations of IL-17 than did the serum of healthy people and that IL-17 abundance correlated with the disease severity of systemic lupus erythematosus.

Variations in the metabolome in response to disease activity of rheumatoid arthritis.

BACKGROUND: Anti-Tumor Necrosis Factor (TNF) therapies are able to control rheumatoid arthritis (RA) disease activity and limit structural damage. Yet no predictive factor of response to anti-TNF has been identified. Metabolomic profile is known to vary in response to different inflammatory rheumatisms so determining it could substantially improve diagnosis and, consequently, prognosis. The aim of this study was to use mass spectrometry to determine whether there is variation in the metabolome in patients treated with anti-TNF and whether any particular metabolomic profile can serve as a predictor of therapeutic response. METHODS: Blood samples were analyzed in 140 patients with active RA before initiation of anti-TNF treatment and after 6 months of Anti-TNF treatment (100 good responders and 40 non-responders). Plasma was deproteinized, extracted and analyzed by reverse-phase chromatography-QToF mass spectrometry. Extracted and normalized ions were tested by univariate and ANOVA analysis followed by partial least-squares regression-discriminant analysis (PLS-DA). Orthogonal Signal Correction (OSC) was also used to filter data from unwanted non-related effects. Disease activity scores (DAS 28) obtained at 6 months were correlated with metabolome variation findings to identify a metabolite that is predictive of therapeutic response to anti-TNF. RESULTS: After 6 months of anti-TNF therapy, 100 patients rated as good responders and 40 patients as non-responders according to EULAR criteria. Metabolomic investigations suggested two different metabolic fingerprints splitting the good-responders group and the non-responders group, without differences in anti-TNF therapies. Univariate analysis revealed 24 significant ions in positive mode (p < 0.05) and 31 significant ions in negative mode (p < 0.05). Once intersected with PLS results, only 35 ions remained. Carbohydrate derivates emerged as strong candidate determinants of therapeutic response. CONCLUSIONS: This is the first study describing metabolic profiling in response to anti-TNF treatments using plasma samples. The study highlighted two different metabolic profiles splitting good responders from non-responders.

Evaluation of low-dose rituximab for the retreatment of patients with active rheumatoid arthritis: a non-inferiority randomised controlled trial.

BACKGROUND: The licensed dose of rituximab in rheumatoid arthritis (RA) is two doses of 1000 mg given 2 weeks apart. A lower dose has never been specifically studied in patients with an inadequate response to anti-tumour necrosis factor (TNF) agents. OBJECTIVE: To compare the efficacy and safety of rituximab repeat treatment with two doses (1000 mg×1 and 1000 mg×2) following initial treatment with 1000 mg×2. METHODS: We set up an open-label, prospective, multicentre, non-inferiority study comprising a non-controlled period (24 weeks) followed by a randomised controlled period (weeks 24-104) in patients with RA and an inadequate response to anti-TNF agents. All patients received one course of rituximab (1000 mg×2) with methotrexate. At week 24, patients achieving a EULAR response (moderate or good) were randomised to rituximab retreatment at 1000 mg×1 (Arm A) or 1000 mg×2 (Arm B). The primary objective measure was disease activity in 28 joints C-reactive protein (DAS28-CRP) area under the curve (AUC) over 104 weeks with a non-inferiority margin defined by 20% (444) of the mean DAS28-CRP AUC (mean±SD 2218±967) of the reference data. RESULTS: The intent-to-treat and per-protocol (PP) populations comprised 143 (A/B: 70/73) and 100 (A/B: 51/49) patients, respectively. The adjusted mean difference in DAS28-CRP AUC (PP) was 51.4 (95% CI -131.2 to 234), demonstrating non-inferiority between arms A and B. The overall rituximab safety profile was similar with both retreatment regimens. CONCLUSIONS: Following a clinical response to a first course of rituximab in RA at the licensed dose of 1000 mg×2, retreatment with rituximab at 1000 mg×1 results in efficacy outcomes that are non-inferior to those achieved with retreatment at 1000 mg×2. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT01126541.

CCL19, a B cell chemokine, is related to the decrease of blood memory B cells and predicts the clinical response to rituximab in patients with rheumatoid arthritis.

OBJECTIVE: Migration of B cells from peripheral blood to the synovium in patients with rheumatoid arthritis (RA) may predict clinical response to rituximab (RTX). We undertook this study to investigate whether serum levels of chemokines involved in B cell trafficking are correlated with blood levels of memory B cells or serum levels of B cell activation biomarkers before B cell depletion and whether chemokine levels predict RTX responsiveness. METHODS: Blood B cell subsets were analyzed by flow cytometry (CD27, IgD), and serum B cell activation biomarkers (rheumatoid factor, anti-cyclic citrullinated peptide, free light chains, IgG, IgA, IgM, and BAFF) were measured in 208 RA patients and 70 control subjects. Serum CCL19, CXCL12, and CXCL13 chemokine levels in patients and controls were determined by enzyme-linked immunosorbent assay. The first course of RTX was administered to RA patients, and the response was evaluated at week 24 according to European League Against Rheumatism (EULAR) criteria. Results were expressed as the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Levels of all chemokines were increased in RA patients compared with controls, and levels were inversely correlated with CD27+ memory B cell frequency. CCL19 and CXCL13 levels correlated with levels of 6 serum B cell biomarkers and 4 serum B cell biomarkers, respectively. By univariate analysis, the CCL19 level was positively associated with EULAR response (OR 1.43 [95% CI 1.08-1.90], P = 0.01). By multivariate analysis, the CCL19 level was predictive of a response to RTX (OR 1.48 [95% CI 1.06-2.06], P = 0.02), but this did not persist after adjustment for autoantibody status. CONCLUSION: CXCL13 and CCL19 reflect blood B cell disturbances and their levels correlate with those of other serum B cell biomarkers. CXCL13 and CCL19 are, therefore, surrogate measures for serum B cell biomarkers in RA. Serum CCL19 measurement is a new hallmark of the B cell-mediated RA subtype and may predict clinical response to RTX.

Association between -871C>T promoter polymorphism in the B-cell activating factor gene and the response to rituximab in rheumatoid arthritis patients.

OBJECTIVE: To determine whether a functional single-nucleotide polymorphism in the B-cell activating factor (BAFF) gene correlates with the response to treatment with rituximab (RTX) in RA. METHODS: SMART is a randomized open trial (NCT01126541) assessing two strategies of re-treatment in patients responding to 1-g infusion of RTX with MTX on days 1 and 15 after failure, intolerance or contraindication to TNF blockers. Among the 224 patients included, 115 provided informed consent, could be genotyped and were included in an ancillary study of SMART assessing European League Against Rheumatism (EULAR) response rate after the first course of RTX according to BAFF-871C>T polymorphism. Baseline clinical factors (patients and disease characteristics) and biologic factors (ESR, CRP, RF, anti-citrullinated peptide antibodies, serum immunoglobulins) were collected. Univariate analyses were performed to assess whether BAFF-871C>T polymorphism was associated with EULAR response at week 24. Results with P < 0.15 obtained in univariate analyses were then included in multivariate analysis adjusted on DAS28 level. RESULTS: Ninety-three patients (81%) were responders, of whom 31 (27%) were good responders. CC genotype was significantly associated with a higher response rate [92% of responders vs 64% for TT genotype, odds ratio (OR) = 6.9; 95% CI 1.6, 29.6; P = 0.03]. These results were also confirmed in RF-positive patients (96% vs 58%, P = 0.006). In multivariate analysis, C allele carriage was independently associated with response to RTX (OR = 4.1; 95% CI 1.3, 12.7; P = 0.017). CONCLUSION: The BAFF-871C>T polymorphism seems to influence the response to RTX in RA patients after failure or intolerance to TNF blockers.

B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study.

OBJECTIVE: To examine whether serum B cell markers can predict response to rituximab, a B cell-depleting monoclonal antibody, in patients with refractory rheumatoid arthritis (RA). METHODS: This rituximab re-treatment dose study (SMART [eSsai MAbthera sur la dose de Re-Traitement]) involved 208 patients with refractory RA. Serum markers of B cell activation (anti-cyclic citrullinated peptide [anti-CCP] antibodies, rheumatoid factor [RF], serum IgG, IgA, and IgM levels, serum κ and λ free light chains, and serum BAFF) were assessed before the first rituximab cycle (1,000 mg on days 1 and 15). Univariate and multivariate analyses were performed to identify factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks. RESULTS: There were 149 responders (72%). Two baseline factors were associated with a EULAR response at 24 weeks in multivariate analysis: the presence of anti-CCP antibodies or RF (odds ratio 3.5 [95% confidence interval 1.6-7.6]) and a serum IgG concentration above normal (odds ratio 2.11 [95% confidence interval 1.02-4.33]), with synergy between them (odds ratio 6.0 [95% confidence interval 2.2-16.2]). CONCLUSION: The presence of RF or anti-CCP antibodies and elevated IgG are 2 simple biomarkers that can be used routinely before therapy to predict response to rituximab in patients with refractory RA.

Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis.

OBJECTIVE: To examine blood B cell subsets in patients with rheumatoid arthritis (RA) prior to B cell depletion therapy and to assess their potential as predictors of clinical response to rituximab (RTX). METHODS: Blood B cell subsets were assessed by flow cytometry in 208 RA patients included in an RTX retreatment study (assessed prior to RTX treatment) and in 47 age-matched controls. Expression of BAFF receptor (BAFF-R) on B cells and serum B cell biomarkers was also measured. B cell subsets and BAFF-R expression were compared between RA patient and control populations. Univariate and multivariate analyses were performed to identify baseline factors associated with a European League Against Rheumatism response 24 weeks after 1 cycle of RTX. RESULTS: Mean ± SD counts of both CD27- naive and CD27+ memory B cells were decreased in RA patients (188.6 ± 121.4/mm(3)) compared with controls (257.3 ± 154.1/mm(3)) (P = 0.001) and were partially restored in patients treated with methotrexate (MTX) plus anti-tumor necrosis factor compared with patients treated with MTX alone. Within the CD27+ memory B cells, the CD27+IgD- switched memory subtype was selectively decreased, irrespective of treatment. The frequency of CD27+ memory B cells correlated inversely with levels of several B cell activation biomarkers in RA. Serum BAFF level and BAFF-R expression was comparable in RA patients and controls. A low baseline CD27+ memory B cell frequency was associated with a greater clinical response to RTX (odds ratio 0.97 [95% confidence interval 0.95-0.99], P = 0.0015). CONCLUSION: In B cell depletion therapy-naive RA patients, a low frequency of CD27+ memory B cells correlated with levels of serum B cell activation biomarkers and may predict response to RTX. These results suggest that low memory B cell frequency may be indicative of a B cell-driven RA subtype that is more sensitive to B cell depletion therapy.

Comparison of the efficacy of sonography, magnetic resonance imaging and conventional radiography for the detection of bone erosions in rheumatoid arthritis patients: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the reproducibility of US and to compare its efficacy with that of MRI and conventional radiography (CR) for the detection of bone erosion in RA patients. METHODS: A systematic literature search was performed in the Medline, Embase and Cochrane databases up to August 2009. Trials evaluating the reproducibility of US for bone erosion detection or comparing the number of erosions detected by the three imaging methods at patient and/or joint level were included. This last parameter was assessed using the odds ratio (OR) and 95% CI with the Mantel-Haenszel method (OR < 1 favours US). We explored the heterogeneity between the studies by subgroup analysis. RESULTS: Twenty-one studies including 913 patients were included in this meta-analysis. Intraobserver and interobserver reproducibility of US for erosion detection was good. US and MRI efficacies were comparable at both joint (OR = 1.19, P = 0.45; seven studies, 869 joints) and patient (OR = 1.76, P = 0.22; nine studies, 338 patients) levels. US detected significantly more erosion than CR at both joint (OR = 0.30, P < 0.00001; 4047 joints studied) and patient (OR = 0.31, P < 0.00001; 592 studied patients) levels. The number of patients to screen in order to detect an additional patient with an erosion in comparison with CR was 4, 95% CI (2.4, 5.9). CONCLUSION: US is more effective for erosion detection than CR and has a comparable efficacy to MRI with good reproducibility.

Serious infections in patients with ankylosing spondylitis with and without TNF blockers: a systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND: Tumour necrosis factor (TNF) blockers are known to increase the risk of serious infections in rheumatoid arthritis. Despite wide use of TNF blockers in ankylosing spondylitis (AS), the infection risk has never been evaluated in this disease. OBJECTIVES: To assess serious infections in patients with AS not exposed and exposed to TNF blockers. METHODS: A systematic literature review up to May 2008 using PubMed, EMBASE and Cochrane Library was performed. All randomised controlled trials (RCTs) published between 1995 and 2008 monitoring serious infections, treated with non-steroidal anti-inflammatory drugs (NSAIDs) or TNF blockers, were included. Infection risks were calculated by naive pooling and for 100 patient-years (pyrs) of exposure. To assess the serious infection risk with TNF blockers, a meta-analysis of RCTs was performed using Mantel-Haenszel's method with several sensitivity analyses. RESULTS: Fourteen RCTs were included (3345 patients). With placebo or NSAIDs (N=2202), two serious infections were observed (0.09%, range 0.01% to 0.3%)-that is, 0.4/100 pyrs. In TNF blocker trials, two serious infections were observed with placebo (2/500, 0.4% (0.0% to 1.4%), ie, 1.0/100 pyrs) versus 14 serious infections with TNF blockers (14/996, 0.7% (0.3% to 1.4%), ie, 1.9/100 pyrs). Meta-analysis of the RCTs showed that the increase in serious infections with TNF blockers compared with placebo was not significant: risk difference=0.4% (-0.8% [corrected] to 1.6%). CONCLUSIONS: The absolute risk of serious infections in patients with AS not exposed to TNF blockers is low. The absolute risk of serious infections in patients receiving TNF blockers is higher, but the difference was found to be not significant, possibly through lack of power. Continued monitoring is necessary.

Safety, efficacy and predictive factors of efficacy of a single intra-articular injection of non-animal-stabilized-hyaluronic-acid in the hip joint: results of a standardized follow-up of patients treated for hip osteoarthritis in daily practice.

AIM: To evaluate, in daily clinical practice, the efficacy and tolerability of a single intra-articular injection of non-animal-stabilized hyaluronic acid (NASHA) in patients treated for symptomatic hip OA (HOA). METHODS: Standardized follow-up (FU). PATIENTS: forty patients suffering from HOA treated by a single intra-articular injection of NASHA in the painful hip under fluoroscopy. EVALUATION: patient global assessment (PGA) and walking pain (WP) on a 100 mm visual analogue scale, WOMAC index, Lequesne index at each visit. STATISTICS: last observation carried forward. Treatment efficacy was assessed using OMERACT-OARSI response criteria, minimal clinically important improvement (MCII), patient acceptable symptom state (PASS) obtained from PGA, WOMAC and WP. Predictive factors of efficacy were also studied. RESULTS: Efficacy evaluation: 34 patients were assessable (mean FU 159 days). All clinical variables (WP, PGA, WOMAC, Lequesne index) decreased significantly between baseline and last evaluation. Twenty-two patients (71%) were classified OMERACT-OARSI responders, 25 subjects (75.8%) were classified PASS+, and 19 (61.3%) fulfilled criteria for MCII. Out of clinical and radiological variables only Lequesne index (p = 0.04) and WOMAC (p = 0.04) at baseline were found to be predictive of treatment efficacy. Safety evaluation: the treatment was well tolerated. There were no severe adverse events related to the treatment or to the procedure. However 15 of the 28 assessable patients experienced transient increase of pain in the target hip during the first week after injection. CONCLUSION: Viscosupplementation of the hip with NASHA is easily feasible in daily clinical practice, safe and well tolerated despite a frequent increase of pain the days following injection. Prospective controlled trials are needed to confirm these data and to evaluate both safety and efficacy of a second course of treatment.

Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis.

OBJECTIVES: Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients. METHODS: Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi. RESULTS: A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, positive predictive values (PPV) of 72%, negative predictive values (NPV) of 82%, positive likelihood ratio (LR+) of 3.35 and negative likelihood ratio (LR-) of 0.28. Lower levels of prealbumin and S100A12 and higher level of platelet factor 4 than the determined cutoff at baseline in RA patients are good predictors for response to TNFi treatment globally as well as to Infliximab, Etanercept and Adalimumab individually. CONCLUSION: A multivariate model combining 3 biomarkers (prealbumin, platelet factor 4 and S100A12) accurately predicted response of RA patients to TNFi and has potential in a daily practice personalized treatment.

A bicentre retrospective study of features and outcomes of patients with reactive arthritis.

OBJECTIVE: Reactive arthritis (ReA) is a sterile arthritis following an extra-articular infection, usually of the gastrointestinal or genitourinary tract. The aim of this study was to assess the incidence and the clinical and therapeutic characteristics of ReA and to compare them with those of a historical cohort. We hypothesised that improved hygiene together with prevention and treatment of sexually transmitted infections may have decreased the incidence of ReA. METHODS: All patients with ReA diagnosed in the University Hospital Centres of Lyon Sud and Besançon from January 2002 to December 2012 were included in the study retrospectively and were compared with ReA patients diagnosed from January 1986 to December 1996 in the same two hospitals. Medical records were reviewed, clinical features, treatments and outcomes were analysed and diagnoses were compared with international diagnostic criteria. RESULTS: Twenty-seven patients were included between 2002 and 2012 compared with 31 between 1986 and 1996. The overall incidence of ReA in patients hospitalised in the rheumatology department did not change, although the current evolution is more severe with development of chronic disease in the form of more frequent spondyloarthritis. While the incidence of Chlamydiae trachomatis has decreased, new microbes are now found to be involved. CONCLUSIONS: ReA still exists and its incidence has been stable over the last 30 years. However, ReA currently more often progress to spondyloarthritis. Our study also highlights the need for diagnostic criteria that accurately detect ReA.

Carbonic anhydrase III: a new target for autoantibodies in autoimmune diseases.

The objective of this study was to identify new autoantibodies that could be useful for the diagnosis of rheumatoid arthritis (RA) using immunoblotting on synovial membrane proteins which represent the best source of candidate RA autoantigens. A new target protein with a molecular weight of 26 kDa was found to be recognized by autoantibodies in RA sera and was identified using MALDI-TOF mass spectrometry and second-dimension electrophoresis as carbonic anhydrase III (CAIII). Three similar protein spots at 26 kDa were recognized by both human sera and monoclonal antibody (mAb) directed against CAIII on immunoblotting using the human recombinant CAIII. Interestingly, CAIII expression within the synovial membrane was not observed in non-RA patients and was differentially expressed among RA patients. The sensitivity of these new autoantibodies for RA, using an immunoenzymatic technique, was 17%. Specificity was high when comparing non-autoimmune diseases (100%), while it was found to be weak (67%) when comparing some other autoimmune diseases, and particularly systemic lupus erythematosus (SLE). In conclusion, this study demonstrates that these new autoantibodies against CAIII are not restricted to RA. However the expression of CAIII in the synovial membrane of RA warrants further investigation of the pathophysiological relevance of this finding.

Clinical significance of anti-histidyl-tRNA synthetase (Jo1) autoantibodies.

The clinical significance of a discovery of anti-histidyl-tRNA synthetase (Jo1) autoantibodies patients was established in the early diagnosis of antisynthetase syndrome (ASS) as the common form of this pathology is characterized by interstitial lung disease (ILD), inflammatory muscle disease, and production of anti-Jo1 autoantibodies. However, the specificity of such autoantibodies has to be evaluated in daily clinical practice. In this study, the clinical and prognostic profiles of 45 patients displaying anti-Jo1 autoantibodies were determined. Among 36 patients with a titer of anti-Jo1 autoantibodies above the cutoff value suggested by the manufacturer (40 AU/mL), three different groups were identified. The first group (n = 26) suffered from a complete or incomplete ASS and showed anti-Jo1 autoantibodies mostly above 60 AU/mL. A second group (n = 7) suffered from another autoimmune disease, that is, a systemic lupus erythematosus, cutaneous lupus and rheumatoid arthritis, and Crohn's disease with anti-Jo1 autoantibodies mostly below 60 AU/mL. The third group (n = 3) did not suffer from any autoimmune disease and presented anti-Jo1 autoantibodies below 60 AU/mL. The nine doubtful cases (titer of anti-Jo1 autoantibodies of 30-39 AU/mL) were from patients with no ASS nor myositis. Only 27 out of 45 patients showed antinuclear antibodies with 15 sera showing a pattern characteristic of anti-Jo1 autoantibodies by indirect immunofluorescence on HEp2 cells. In conclusion, this study underlines the need to search for anti-Jo1 autoantibodies even if antinuclear antibodies are negative by indirect immunofluorescence and underlines the usefulness of anti-Jo1 antibodies of titer above 60 AU/mL in the diagnosis of complete or incomplete ASS.

A new target for autoantibodies in patients with rheumatoid arthritis.

Early treatment of rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs can achieve a better disease outcome and reduce the severity of joint damage. The presence of autoantibodies in patient sera can precede onset of the disease and thus be predictive of the development of RA. To date, known autoantibodies in RA are positive in only 50-60% of RA patients at onset of disease and even less before the onset of any RA symptom. The aim of this study was to identify new antibodies that could be useful for the diagnosis of RA using synovial membrane proteins, which represent the best source of candidate RA autoantigens. The humoral reactivity of sera from RA patients was explored using immunoblotting on extracted proteins obtained from synovial membranes from RA after synovectomy or arthroplasty. A new target protein with a molecular weight of 26 kDa was found to be recognized by autoantibodies in RA sera. This protein was identified using MALDI-TOF mass spectrometry and two-dimensional electrophoresis as carbonic anhydrase III with a high level of confidence. In conclusion, this study demonstrates new autoantibodies in RA patients that are directed against carbonic anhydrase III. The sensitivity and specificity of these new autoantibodies for RA have to be further evaluated.

Factors influencing the use of tocilizumab as monotherapy in patients with rheumatoid arthritis in a real-life setting: results at 1†year of the ACT-SOLO study.

INTRODUCTION: Using a biologic disease-modifying antirheumatic drug (bDMARD) as monotherapy in clinical practice for patients with rheumatoid arthritis (RA) is common and recognised by health authorities although current guidelines recommend to combine them with conventional synthetic (cs)DMARDs. This study mainly aimed to search for real-life factors influencing the use of tocilizumab as MONO or in combination (COMBO). METHODS: In this non-interventional, prospective, national, multicentre study, data were collected every 3 months over a 12-month period in RA patients starting tocilizumab. The proportion of monotherapy patients was described, together with significant explicative factors. RESULTS: Among the 577 analysed patients recruited from January 2012 to August 2013 (228 monotherapy patients; 40%), 79% were women, mean RA duration was 11±9 years, previous RA treatments included bDMARDs and csDMARDs in 75% of cases and mean Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) was 5.2±1.3 at inclusion. Explicative factors for monotherapy were at least 65 years (OR=1.47, p=0.0485), no methotrexate within the two last years (OR=5.96, p<0.0001), past severe infection (OR=1.99, p=0.0272) and higher baseline DAS28-ESR (OR=1.22, p=0.0086). Regarding clinical results (DAS28-ESR, Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) low disease activity and remission; ACR20/50/70 and European League Against Rheumatism (EULAR) response; Health Assessment Questionnaire Disability Index (HAQ-DI) score), no relevant differences between monotherapy and combination patients were observed at 1 year. A total of 23 tocilizumab-treated patients (4%) experienced serious infections; no new safety signals were noted with no differences between groups. CONCLUSIONS: ACT-SOLO confirms the high proportion of RA patients receiving tocilizumab as MONO in clinical practice. The study also showed that clinical results at 1 year were similar between MONO and COMBO patients in a real-life setting. TRIAL REGISTRATION NUMBER: NCT01474291.

Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis.

BACKGROUND: The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 (IRF5 and IRF7), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24). METHODS: Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response. Because the variant TNFSF13B rs9514828 was previously found associated with RTX response in the same population, it was included in the analysis. RESULTS: The combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B rs9514828 was strongly associated with good/moderate EULAR response to RTX at W24: p=9.34×10-6, OR 11.37 (95% CI 4.03 to 35.28), positive predictive value 91% and negative predictive value 54%. CONCLUSION: Our results support the contribution of the IRF5, SPP1 and TNFSF13B genotypic combination in the response to RTX for RA at W24.

Isolated positive anti-SS-B autoantibodies are not related to clinical features of systemic autoimmune diseases: Results from a routine population survey.

OBJECTIVE: To assess in clinical practice the frequency and diagnosis associated with the SS-B-positive/SS-A negative autoantibody profile. METHODS: We analyzed a one-year consecutive population of 624 patients referred by clinicians to the immunology laboratory to investigate anti-SS-A and/or anti-SS-B autoantibodies, who were detected using luminex technology. Data were analyzed for patients with isolated anti-SS-B autoantibodies. The clinical characteristics and diagnosis of connective tissue diseases (CTD) were retrieved according to the international criteria. RESULTS: Among 1173 sera positive for anti-SS-A and/or anti-SS-B autoantibodies from 624 patients, we identified 84 patients (13.5%) that had isolated anti-SS-B. Among the 75 patients positive for anti-SS-B with known clinical data, 15 were diagnosed with a CTD (20%) including 4 systemic lupus erythematosus (5%), 4 rheumatoid arthritis (5%), 2 idiopathic inflammatory myositis (3%), 1 primary Sjögren's syndrome pSS (1%), 1 systemic sclerosis (1%), 2 undefined CTD (3%), and 1 mixed CTD (1%). Among the 60 other patients, 18 had non-CTD autoimmune diseases and 42 had non-autoimmune diseases. Within the CTD population, the presence of isolated anti-SS-B was not significantly associated to characteristic indicating a specific syndrome. There was no association between diagnosis of CTD and level of anti-SS-B autoantibodies (p = 0.70). Arthralgia was the more frequent sign and encountered in 10 patients (67%), of whom 3 had arthritis. CONCLUSION: The presence of anti-SS-B, without anti-SS-A autoantibodies using luminex technology, was not associated with CTD, especially pSS, in daily clinical practice. Our data suggests that the SS-B serological profile is not contributive for the classification criteria of pSS.