Impact of assessment of bone status before corrective surgery of lumbar spine in patients over 50 years old.

Background and objective: There is absence of data on the prevalence of osteoporosis before corrective surgery of the lumbar spine. We do not know the impact of bone assessment before corrective spine surgery, regarding the prevalence of osteoporosis, risk factors for osteoporosis, and prescription of osteoporotic treatment. Our objective was to evaluate the impact of assessment of bone status before corrective surgery of the lumbar spine. Methods: This retrospective study was conducted over a period of 30 months. Patients included were over 50 years old and had been referred to rheumatology consultation prior to corrective surgery of the lumbar spine with osteosynthesis, for scoliosis or spondylolisthesis. Assessment of bone status consisted in looking for risk factors for osteoporotic fracture, performing bone densitometry with the calculation of TBS (trabecular bone score) and the possible introduction of treatment for osteoporosis. Data were collected on complications related to bone fragility during follow-up. Results: Twenty-eight patients with a median age of 71.2 years (55.5-84.8) were included; 89% were women. T score was <-2.5 in 14.3% (4/28) and -1 to -2.5 in 42.9% (12/28) on at least one of the three sites analyzed. Fifty percent of patients had a TBS <1.2, a history of more than four falls per year, a duration of more than 20 s in the Timed Up and Go Test, and/or sedation treatment. Vitamin-calcium supplementation and treatment for osteoporosis were prescribed in 71.4% and 17.8% of cases, respectively. During follow-up, 3 patients had one or more osteoporotic vertebral fractures and 4 patients had loosening of implanted devices. Conclusion: Despite a low prevalence of densitometric osteoporosis and therapeutic management, one in four patients had a bone complication, suggesting the superiority of TBS as an indicator of bone status.

Switching from an anti-TNF monoclonal antibody to soluble TNF-receptor yields better results than vice versa: An observational retrospective study of 72 rheumatoid arthritis switchers.

OBJECTIVES: To evaluate the benefits for rheumatoid arthritis (RA) patients of switching from one tumor necrosis factor inhibitor (TNFi) to another based on reason for change (primary failure, escape or intolerance) and molecule-switching order. METHODS: Between 2000 and 2008, 356 RA patients prescribed a TNFi (infliximab [IFX], etanercept [ETA] or adalimumab [ADA]) and undergoing standardized evaluation were included in this retrospective study. Detailed demographic, clinical and biological data were collected before first biologic use and ≤6 months later to evaluate response based on EULAR-criteria. Primary failure, escape or intolerance of first TNFi triggered switch to another TNFi, the response of which was evaluated 6 months later. Propensity score then measured any interaction with baseline variables. RESULTS: Of the 356 RA patients, 38 switched from IFX/ADA to ETA, 26 from ETA to IFX/ADA, and eight from one monoclonal antibody (mAb; IFX/ADA) to another. Clinical parameters for switchers and non-switchers were comparable. Switchers changed therapies because of primary failure (36.1%), escape (33.3%), or intolerance (30.6%), with no difference found in these subgroups. More switchers responded to the second TNFi than the first (P<0.01), respectively, regardless of switch (ETA to IFX/ADA: 50 vs. 23.1% [P<0.05]; IFX/ADA to ETA: 57.9 vs. 15.8% [P<0.001]) or reason for changing. In addition, DAS28 decreased more with the second antagonist (P<0.001) and regardless of molecules switched (P<0.01). Survival of the second TNFi was significantly longer with switch from mAb to the soluble receptor than vice versa (P<0.05). DISCUSSION: Overall, any switching from one TNFi to another, especially mAb to soluble receptor, was often beneficial for RA patients.

Validation of the 2010-ACR/EULAR -classification criteria using newly EULAR-defined erosion for rheumatoid arthritis on the very early arthritis community-based (VErA) cohort.

OBJECTIVE: To validate the 2010-ACR/EULAR criteria for rheumatoid arthritis (RA), taking into account the recent EULAR definition of "erosive disease", on the 310 patients comprising the very early arthritis cohort (VErA). METHODS: 2010-criteria performances were tested by first strictly applying its three items successively: ≥ 1 clinical synovitis/another disease(s)/score ≥ 6/10), then the typical erosion grid without obtaining a score of ≥ 6 to diagnose RA. We tested successively: no erosion (S1), ≥ 1 erosion(s) (S2), EULAR-defined erosive disease (S3). Two gold standards were used: expert diagnosis at six years and EULAR erosive disease at two years. RESULTS: At inclusion, median age was 52 years; median RA duration 4.2 months. 2010-ACR/EULAR criteria, including EULAR-defined erosive disease applied at baseline, classified comparable numbers of patients as the 1987 criteria (P=0.27). Using expert diagnosis at six years, more patients were classified as RA with S2 than 1987-ACR criteria (P<0.04). In contrast, sensitivity and specificity indicated that 2010-ACR/EULAR-S3 criteria performed slightly but not significantly better than 1987-ACR criteria. On ROC curves, a score ≥ 6 correctly classified RA. When EULAR-defined erosion at two years was the gold standard, the 1987-ACR, the 2010-S1, -S2 and -S3 criteria performed comparably. CONCLUSIONS: Using the very early community-based, conservatively treated VErA cohort, the strict application of 2010-ACR/EULAR criteria using the new EULAR definition of erosive disease or not performed slightly but not significantly better than the 1987-ACR criteria.

Efficacy of anti-TNF in patients with spondyloarthritis in absence of any imaging sign.

OBJECTIVE: Some clinical pictures satisfy spondyloarthritis criteria without any detected imaging signs and the question sometimes arises in clinical daily practice if biologics should be started. Our aim was to evaluate anti-TNF efficacy in patients with clinical but not imaging (radiographic, CT-scan, MRI) signs of spondyloarthritis. METHODS: This retrospective study concerned patients with axial spondyloarthritis fulfilling European Spondyloarthritis Study Group (ESSG) criteria, treated with anti-TNF after failure of conventional therapies. Therapeutic responses, rated according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)-50% or 20 mm and ASAS-20 or -40 definitions, were evaluated after 12 months. Factors associated with those responses were also sought. Propensity score was used to check thereafter whether there were interactions with some baseline variables. RESULTS: Among 385 patients included, 257 with imaging signs had significantly more frequent therapeutic responses (P=0.0005). About 40% of the spondyloarthritis patients without imaging signs responded to anti-TNF. The response rate was significantly higher in HLA-B27 carriers with initial imaging signs (P=0.028). Furthermore, responders were younger at biotherapy onset, with lower Bath Ankylosing Spondylitis Functional Index (BASFI) and pain visual analog scale score, and higher C-reactive protein (CRP), compared to non-responders. After weighted calculation, the prediction of response to TNF-blockers was quite similar in both groups. CONCLUSION: The percentage of patients with exclusively clinical signs who responded to anti-TNF was far from negligible. Regardless the HLA-B27 status, having imaging signs of spondyloarthritis does not provide a superiority of response to anti-TNF compared to the absence of imaging sign. The absence of any imaging sign in patients with spondyloarthritis should therefore not lead to the exclusion of anti-TNF therapy.

Synovium CD20 expression is a potential new predictor of bone erosion progression in very-early arthritis treated by sequential DMARDs monotherapy -- a pilot study from the VErA cohort.

OBJECTIVE: Because available biomarkers (rheumatoid factors [RF], anti-cyclic citrullinated autoantibodies [anti-CCP2], erythrocyte sedimentation rate at 1st hour [ESR]/C-reactive peptide [CRP] and bone erosions) are insufficient to predict rheumatoid arthritis (RA) structural damage, to determine whether synovium expression of greater or equal to 1 markers could constitute new prognostic factor(s). METHOD: The study was conducted on 18 prospectively enrolled disease-modifying anti-rheumatic drug (DMARD)- and glucocorticoid-naïve, VErA cohort patients with very-early arthritis (median duration: 4months). Recorded at baseline were: clinical and biological (serum ESR, CRP, RF-isotypes, anti-CCP2, osteoprotegerin, receptor activator of nuclear κB-ligand [RANK-L] and cartilage oligomeric matrix protein [COMP] levels) data; synovium expression (HLA-DR, CD163, CD3, CD20, VEGF, osteoprotegerin, RANK-L, Bcl2 and global inflammation index) for a metacarpophalangeal joint-synovium biopsy. Baseline and 3-year hand-and-foot X-rays were graded with the van der Heijde-modified-Sharp score; the judgment criterion was its progression during follow-up. Pearson's product moment correlation statistics were used to test for association between paired samples. RESULTS: A baseline, a significant relationship was found between erosive damage and markers of B-cell activation, notably the synovium CD20 expression (r=0.68; P=0.0001). Quantified by the modified-Sharp erosion score variation, the 3-year structural damage progression was significantly correlated with: serum levels of RF-IgG (r=0.75; P=0.0003), -IgM (r=0.69; P=0.001), anti-CCP2 (r=0.53; P=0.02) and RANK-L (r=0.61; P=0.007); synovium CD20 expression (r=0.70; P=0.001). CONCLUSION: This analysis of the prognostic value of a large panel of synovium markers in a limited sample of prospectively followed, well-documented patients suggested that both synovial CD20 and serum RANK-L levels might be new predictors of structural damage progression in very-early RA.

Combining anti-cyclic citrullinated peptide with the American College of Rheumatology 1987 criteria failed to improve early rheumatoid arthritis diagnosis in the community-based very early arthritis cohort.

OBJECTIVES: To test the performances of combining anti-CCP second generation (CCP2) with ACR 1987 classification criteria and to diagnose early RA in a community-based very early arthritis (VErA) patient cohort. METHODS: The VErA cohort comprised 310 patients (median age 52 years; 68.1% women; median symptom duration 4.2 months; glucocorticoid- and DMARD naïve) conservatively treated during the first 2 years. At 6 years of follow-up, a three-expert committee classified the patients into three groups: RA, other classified arthritis (OCA) or unclassified arthritis (UA). We calculated the performances of the different sets, including anti-CCP2 positivity, while retaining or deleting RF and rheumatoid nodule components with ACR 1987 criteria for early RA diagnosis. Models were subjected to receiver operating characteristics curve and logistic regression analyses to try to identify relevant sets able to classify very early RA. RESULTS: At 6 years, 149 patients were diagnosed as RA and 119 as non-RA (95 OCA and 24 UA). The original ACR 1987 criteria had 77.9% sensitivity and 64.7% specificity for the RA diagnosis at 6 years. The modified set excluding rheumatoid nodules, including anti-CCP2 positivity and retaining RF performed significantly better than ACR 1987 criteria, with 79.9% sensitivity and 64.7% specificity and with a larger area under the curve. However, in the zone of interest, i.e., ≥4/7 criteria, the curves for these sets were superimposed. CONCLUSIONS: Adding anti-CCP2 positivity and deleting rheumatoid nodules failed to improve the performances of ACR 1987 classification criteria for the diagnosis of early RA.

Gene profiling predicts rheumatoid arthritis responsiveness to IL-1Ra (anakinra).

OBJECTIVES: The overall non-response rate to biologics remains 30-40% for patients with RA resistant to MTX. The objective of this study was to predict responsiveness to the anakinra-MTX combination by peripheral blood mononuclear cell gene profiling in order to optimize treatment choice. METHODS: Thirty-two patients treated with anakinra (100 mg/day s.c.) and MTX were categorized as responders when their 28-joint DAS (DAS-28) had decreased by ≥1.2 at 3 months. Pre-treatment blood samples had been drawn. RESULTS: For seven responders and seven non-responders, 52 microarray-identified mRNAs were expressed as a function of the response to treatment, and unsupervised hierarchical clustering correctly separated responders from non-responders. The levels of seven of these 52 transcripts, as assessed by real-time, quantitative RT-PCR, were able to accurately classify 15 of 18 other patients (8 responders and 10 non-responders), with 87.5% specificity and 77.8% negative-predictive value for responders. Among the 52 genes, 56% were associated with IL-1ß. CONCLUSION: This predictive gene expression profile was obtained with a non-invasive procedure. After further validation in other cohorts of patients, it could be proposed and used on a large scale to select likely RA responders to combined anakinra-MTX. Trial registration. Clinical Trials; NCT00213538 (http://www.clinicaltrials.gov).

A 3 mg/kg starting dose of infliximab in active spondyloarthritis resistant to conventional treatments is efficient, safe and lowers costs.

OBJECTIVE: We assessed the efficacy, tolerance and cost of a 3 mg/kg starting dose of infliximab for ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: We retrospectively followed-up 45 biologic-naive consecutive patients (11 with axial AS, 24 with axial and peripheral [mixed] AS and 10 with PsA) who were treated between 2002 and 2005 with a 3 mg/kg dose of infliximab after failure of conventional therapies. The following variables were recorded: visual analog scale (VAS) scores of patient's global (G) and pain (P) assessment, duration of early morning stiffness (EMS), disease activity (BASDAI) and functional disability (BASFI). Treatment responses were assessed at 6 and 12 months using the AS assessment score (ASAS)-20% and -40% criteria and BASDAI-50. RESULTS: Baseline characteristics of the 29 men and 16 women were (median [range]): G-VAS, 70 [13-100]; P-VAS, 70 [13-100]; EMS, 60 [0-180] minutes; BASDAI, 64.4 [23.9-100]; BASFI, 57.2 [3.5-98.5]. All manifestations regressed significantly (p<0.0001) for 39 (86.7%) and 24 (53.5%) patients at 6 and 12 months, respectively; 26 (57.8%) had achieved ASAS-20 responses at 6 months that persisted at 1 year for 20 (44.4%); 19 (42.2%) and 12 (26.7%) satisfied BASDAI 50 criteria at 6 and 12 months, respectively. Interestingly, almost 30% still received low-dose infliximab after 4 years of follow-up. CONCLUSION: An initial dose of 3 mg/kg of infliximab significantly attenuated AS and PsA manifestations in>40% of the patients, making use of this dose highly advantageous in terms of safety and 33% lower cost.

Serum IgA rheumatoid factor and pyridinoline in very early arthritis as predictors of erosion(s) at two years: a simple model of prediction from a conservatively treated community-based inception cohort.

OBJECTIVE: To identify, in conservatively treated, very early arthritis patients, predictors of ≥1 erosion(s) at 2 years, and to construct a prediction model. METHODS: Community-based adults (n=310) who had never taken disease-modifying antirheumatic drugs (DMARDs) or steroids with swelling of ≥2 joints persisting for >4 weeks and lasting <6 months were recruited. Erosion status was assessed at 0, 6, 12, and 24 months; evaluations were comprised of clinical criteria (Disease Activity Score, Health Assessment Questionnaire), C-reactive protein level, erythrocyte sedimentation rate, autoantibodies, bone and cartilage markers, hand densitometry, and HLA class II shared epitopes. Patients meeting American College of Rheumatology rheumatoid arthritis (RA) criteria or with undifferentiated arthritis (UA) were followed and treated conservatively: one-third of RA patients and three-fourths of UA patients received no DMARDs during 2 years; a biologic agent was given to 1.8% of the patients during the first year. The main judgment criterion was ≥1 erosion(s) at 2 years. RESULTS: At 2 years, 219 patients were assessed; 31.3% with RA and 10.6% with UA had ≥1 erosion(s). Logistic regression analysis at that time showed erosion(s) strongly associated with serum IgA rheumatoid factor (IgA-RF) and pyridinoline levels for the 190 patients with no baseline erosions, with the corresponding receiver operating characteristic curve having an area under the curve of 0.77 (95% confidence interval 0.64-0.86). A prediction model was constructed with IgA-RF thresholds of 5 and 25 IU/ml and a pyridinoline threshold of 10 nM/liter; odds ratios ranged from 1 for IgA-RF<5 IU/ml and pyridinoline <10 nM/liter to 50.75 for the association of IgA-RF≥5 IU/ml and pyridinoline≥10 nM/liter. CONCLUSION: This model, using serum IgA-RF and pyridinoline concentrations, was able to predict≥1 erosion(s) at 2 years in very early arthritis patients.

Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis.

As indicators of responsiveness to a tumour necrosis factor (TNF)alpha blocking agent (infliximab) are lacking in rheumatoid arthritis, we have used gene profiling in peripheral blood mononuclear cells to predict a good versus poor response to infliximab. Thirty three patients with very active disease (Disease Activity Score 28 >5.1) that resisted weekly methotrexate therapy were given infliximab at baseline, weeks 2 and 6, and every 8th week thereafter. The patients were categorized as responders if a change of Disease Activity Score 28 = 1.2 was obtained at 3 months. Mononuclear cell RNAs were collected at baseline and at three months from responders and non-responders. The baseline RNAs were hybridised to a microarray of 10,000 non-redundant human cDNAs. In 6 responders and 7 non-responders, 41 mRNAs identified by microarray analysis were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated these responders from non-responders. The informativeness of 20 of these 41 transcripts, as measured by qRT-PCR, was re-assessed in 20 other patients. The combined levels of these 20 transcripts properly classified 16 out of 20 patients in a leave-one-out procedure, with a sensitivity of 90% and a specificity of 70%, whereas a set of only 8 transcripts properly classified 18/20 patients. Trends for changes in various transcript levels at three months tightly correlated with treatment responsiveness and a down-regulation of specific transcript levels was observed in non-responders only. Our gene profiling obtained by a non-invasive procedure should now be used to predict the likely responders to an infliximab/methotrexate combination.

Management of infusion reactions to infliximab in patients with rheumatoid arthritis or spondyloarthritis: experience from an immunotherapy unit of rheumatology.

OBJECTIVE: To suggest recommendations for management of acute infusion reactions induced by infliximab in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: In total, 203 patients were treated with infliximab (120 ml/h). Prevalence of acute infusion reaction was evaluated. To manage these conditions, recommendations were devised according to the type and the severity of clinical manifestations, which were classified beforehand in 2 groups: A (hypertension, pruritus, sudden flush, vomiting, tachycardia or bradycardia, shivers, fever) and B (urticaria, tickling throat, Quincke's edema, dyspnea, and hypotension). Recommendations were based mainly on adjustment of the infusion rate. RESULTS: It was observed that 23/203 patients (11.3%) had acute infusion reactions. Among them and prior to our recommendations, infliximab was completely discontinued in 8/23 patients. After our recommendations were implemented, 15/23 patients presented an acute infusion reaction: 8 and 7 patients with symptoms of Group A and B, respectively. In Group A (8 patients), reducing the infusion rate to 60-80 ml/h led to disappearance of symptoms; the modified treatment was then maintained. In Group B (7 patients), the infusion was immediately stopped and appropriate drugs were administered. Once clinical manifestations were alleviated, the infusion was resumed (60 ml/h). Prior to subsequent infusions (60 ml/h), a premedication was administered. CONCLUSION: Based on these recommendations, infliximab could be maintained with great efficacy on disease activity in every patient with an acute infusion reaction. Our recommendations permit sustained administration of infliximab and allow every patient to benefit from this therapy.

Association between the TNFRII 196R allele and diagnosis of rheumatoid arthritis.

Tumour necrosis factor (TNF)-alpha plays a key role in the pathogenesis of rheumatoid arthritis (RA). It binds to two receptors, namely TNF receptor (TNFR)I and TNFRII. Several studies have suggested an association between TNFRII 196R/R genotype and RA. The objective of the present study was to evaluate the predictive value of the TNFRII 196R allele for RA diagnosis and prognosis in a cohort of patients with very early arthritis. We followed up a total of 278 patients recruited from the community, who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for less than 6 months, and who had not received disease-modifying antirheumatic drugs or steroid therapy. At 2 years, patients were classified according to the American College of Rheumatology criteria. All patients were genotyped with respect to TNFRII 196M/R polymorphism. Radiographs of hands and feet (read according to the modified Sharp method) and the Health Assessment Questionnaire were used to quantify structural and functional severity. The cohort of 278 patients was found to include 156 and 122 RA and non-RA patients, respectively. The TNFRII 196R allele was found to be associated with RA (P = 0.002). However, progression of radiographic severity and Health Assessment Questionnaire scores over 1 year did not differ between carriers of the 196R allele and noncarriers. Our findings suggest that the TNFRII 196R allele may be associated with RA diagnosis but that it does not predict early radiographic progression or functional severity in patients with very early, unclassified arthritis.

Septic arthritis due to Actinomyces naeslundii: report of a case.

In a man with osteoarthritis of the knee, Actinomyces naeslundii septic arthritis developed after intra-articular injection of hyaluronate. Actinomyces is an anaerobic Gram-positive rod. The outcome was favorable after treatment with two antibiotics and arthroscopy. The nature of the organism and its location to a joint are unusual features of this case, which illustrates the need to search for a septic complication before accepting a diagnosis of inflammation related to hyaluronate injection.

Septic arthritis of the hip caused by Yersinia enterocolitica: a case report.

We report a case of bacteriologically documented hip infection caused by Yersinia enterocolitica. A 67-year-old male with a history of valvular disease was admitted for pain and motion range limitation in the left hip with a fever. No organisms were recovered by needle aspiration, but Yersinia enterocolitica grew in joint fluid obtained by surgical arthrotomy. Investigations of the gastrointestinal tract were normal, and there was no evidence of endocarditis. After 6 weeks of appropriate antibiotic therapy and immobilization with transtibial traction, the clinical and laboratory test abnormalities improved. However, the patient died from an intercurrent condition. Y. enterocolitica, a well-known cause of reactive arthritis, can cause septic arthritis.