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Background: The lack of validated tools to predict rheumatoid arthritis (RA) disease course warrants the development of new reliable biomarkers. We have previously detected increased semaphorin 4A (SEMA4A) expression in endothelial cells, synovial tissue, and serum of patients with RA. In addition, SEMA4A serum levels correlated with multiple clinical, biological, and power doppler ultrasound markers of disease activity. Our aim was to evaluate circulating SEMA4A for the prediction of outcomes in patients with RA.Methods: A first cohort included between May 2016 and February 2018 101 consecutive RA patients followed up on an annual basis until August 2021. Baseline SEMA4A concentrations were analyzed according to disease progression defined for the purpose of this study by the occurrence of patient-reported flares and initiation or change of targeted therapy. A second cohort included 40 consecutive RA patients who initiated new therapy because of insufficient disease control. The course of SEMA4A levels was studied between baseline and month 3 according to treatment response. Results: During a follow-up period of 41±15 months, disease progression occurred in 26/101 patients in the first cohort. Increased baseline SEMA4A levels were identified as an independent predictor of disease progression (hazard ratio, HR: 2.71, 95%CI 1.14-6.43). The highest predictive value of disease progression was obtained with the combination of increased circulating SEMA4A and/or DAS28-CRP>3.2 and/or synovial hyperemia on doppler ultrasound (HR: 10.42, 95%CI 1.41-76.94). SEMA4A was also predictive of disease progression in patients with a DAS28 Conclusion: circulating SEMA4A appears as an appealing biomarker in RA with ability to predict disease progression, and with association with response to therapy.

BACKGROUND: In people with chronic low back pain (cLBP) and active discopathy, glucocorticoid intradiscal injection (GC IDI) reduces LBP in the short-term. Lumbosacral immobilization may be useful to obtain long-term results. OBJECTIVE: To assess the feasibility of a lumbosacral immobilization using a pantaloon cast following GC IDI in people with cLBP sand active discopathy. METHODS: We conducted a retrospective feasibility study. Participants were allocated to experimental or control groups by preferences. The experimental group received lumbosacral immobilization using a custom-made pantaloon cast worn continuously for one week following a GC IDI of 25 mg of prednisolone acetate. The control group received GC IDI alone. The primary endpoint was the feasibility of lumbosacral immobilization assessed by the rate of refusal and early withdrawal of the cast. RESULTS: Twelve patients were offered lumbosacral immobilization following GC IDI: the rate of refusal was 3/12 (25.0%) and was 3/9 (33.3%) of early withdrawal. Mean (95% CI) acceptability of the procedure was 55.0 (26.9–83.1)/100 in the experimental group (N= 6) and 61.6 (25.1–98.2)/100 in the control group (N= 6). CONCLUSIONS: We found high rates of refusal and early withdrawal of the lumbosacral immobilization using a pantaloon cast following GC IDI in people with nonspecific cLBP and active discopathy.

• Objectives: to estimate the seroprevalence of SARS-CoV-2 infection in patients with rheumatic diseases and to specify the proportion of asymptomatic and symptomatic forms of COVID-19. • Methods: we screened for SARS-CoV-2 infection among spondyloarthritis (SpA, n=143) or rheumatoid arthritis (RA, n=140) patients in our outpatient clinic at Cochin Hospital in Paris between June and August 2020. We performed a qualitative SARS-CoV-2 serological test which detects IgG directed against the N nucleocapsid protein (anti-N) and, for some patients, against the Spike protein (anti-S). Descriptive analyses were managed. • Results: during June–August 2020, the SARS-CoV-2 seroprevalence rate in our population was 2.83% (8/283 patients) without significant difference between RA and SpA patients (2.14% and 3.5% respectively). We report 11 out of 283 patients (3.8%) with a diagnosis of SARS-CoV-2 infection. Among these 11 patients, 1 patient was asymptomatic (9%) with a confirmed diagnosis of COVID-19 by anti-S serology. Of the 283 patients, 85% were under bDMARDs, mainly on rituximab (RTX) (n=44) and infliximab (IFX) (n= 136). • Conclusions: the seroprevalence of SARS-CoV-2 in patients with rheumatic diseases, mainly under bDMARDs treatments, was 2.83%. Among infected patients, 9% were asymptomatic. Detecting SARS-CoV-2 infections could be based on the strategy using patients’ interview and anti-N serology.

Introduction La prévalence des formes asymptomatiques d’infection COVID-19 en population générale est mal connue à ce jour (

We aimed to estimate the amount of scarring in the liver with the fibrosis-4 (FIB-4) index in patients with rheumatoid arthritis (RA) with special interest in methotrexate (MTX) influence.This was a cross-sectional monocentric study including successive RA patients recruited for a 12-month period. Data on liver function, disease activity, hepatotoxic and cardiovascular risk factors were systematically collected. The FIB-4 index was calculated according the following formula: (age(years)× AST(U/L)/platelet (PLT) (109/L)×√ALT(U/L)).We included 170 patients with established RA: 141 (83%) were women with a mean age of 59±12 years and mean disease duration of 15±11 years. The FIB-4 was low and not significantly different between patients receiving MTX (n=102), patients previously treated with MTX (n=39) and patients never treated with MTX (n=29). No correlation was observed between FIB-4 values and cumulative MTX dose (r=0.09, p=0.271). No relationship was observed between FIB-4 and MTX treatment duration. The FIB-4 index was found significantly increased in patients receiving leflunomide (n=24), (median (range) 1.58 (0.46-3.16) vs. 1.18 (0.54-3.40), p=0.019) and tocilizumab (n=14), (median (range) 1.82 (0.75-3.73) vs. 1.18 (0.54-3.40), p=0.005) compared to patients not receiving DMARDs (n=29). Multivariate logistic regression analyses revealed an independent association between increased FIB-4 (1.45) and male gender, low disease activity, and treatment with leflunomide and tocilizumab.RA patients with long-term maintenance MTX therapy have low FIB-4 values suggesting that MTX is not associated with an increased risk of advanced liver fibrosis. Increased FIB-4 values have been detected in leflunomide- and tocilizumab-treated patients, which will deserve dedicated further investigations.

We aimed to compare serum biomarkers of inflammation, redox status and cartilage degradation between chronic low back pain (cLBP) patients with and without Modic 1 changes. We used a convenience sample of patients recruited from a single center, case-control study, conducted in a tertiary care center. From December, 2014 to May, 2016, 2,292 patients were consecutively screened, 34 met inclusion criteria and were prospectively enrolled in the present study. Cases (n = 13) were defined as patients with Modic 1 changes detected on MRI and controls (n = 21) as cLBP patients without (Modic 0). To assess serum biomarkers of inflammation, redox status and cartilage degradation, fasting serum samples were collected in a standardized manner and analyzed by immunoassays and spectrophotometry. Mean (95% CI) age was 44.1 (40.0–48.1) years and mean LBP duration was 72.5 (53.0–91.9) months. Serum biomarkers of inflammation (IL-1β, IL-6, IL-8 and TNF-α), redox status (total thiols, advanced oxidation protein products and carbonyl groups) and cartilage degradation (Coll2-1 and Coll2-1NO2) did not differ between cLBP patients with and without Modic 1 changes. In summary, we did not find any differences in serum biomarkers between cLBP patients with and without Modic 1 changes. Interpretation is limited by convenience sampling and small sample size.

Background Intervertebral disc therapies (IDT) for the management of non-specific chronic low back (NScLBP) pain are raising interest (1). Objectives To review evidence on the benefits and harms of IDT in people with NScLBP. Methods We searched 4 databases and conference abstracts, from inception to July 2018, for randomized trials of IDT versus placebo interventions, active comparators or usual care. Two independent investigators extracted data and assessed the risk of bias. The primary outcome was LBP intensity at short, intermediate and long terms (2). Secondary outcomes were LBP-specific activity limitation and safety (3). Our review was registered with the International Prospective Register of Systematic Reviews (CRD42019106336). Results Of 17 eligible trials, 5 trials (436 patients) assessed glucocorticoid (GC) IDT and were included in a quantitative synthesis. Twelve trials assessed IDT of other products including ozone (n=2, 140 patients), methylene blue (n=1, 72 patients), stems cells (n=1, 24 patients), glycerol (n=1, 11 patients), etanercept (n=2, 96 patients), tocilizumab (n=1, 60 patients), platelet-rich plasma (n=1, 47 patients), chymopapaine (n=1, 39 patients) and rhGDF-5 (n=2, 55 patients) and were included in a narrative synthesis. Standardized mean differences (SMD) of GC IDT for LBP intensity and activity limitations were -1.33 (-2.34;-0.32) and -0.76 (-1.85;0.34) at short-term, -2.22 (-5.34;0.90) and -1.60 (-3.51;0.32) at intermediate-term and -1.11 (-2.91;0.70) and -0.63 (-1.68;0.42) at long-term, respectively. OR of GC IDT for serious and minor adverse events were 1.13 (0.20; 4.59) and 0.97 (0.49;1.91). Conclusion GC IDT are associated with a reduction in LBP intensity at short-term in people with NScLBP. Positive effects are not sustained. There is no effect on activity limitations. References [1] Knezevic NN, Mandalia S, Raasch J, Knezevic I, Candido KD. Treatment of chronic low back pain - new approaches on the horizon. J Pain Res. 2017;10:1111-23. [2] Chiarotto A, Boers M, Deyo RA, Buchbinder R, Corbin TP, Costa LOP, et al. Core outcome measurement instruments for clinical trials in nonspecific low back pain. Pain. 2018;159(3):481-95. [3] Team QAaSM. Safety of medicines : a guide to detecting and reporting adverse drug reactions : why health professionals need to take action. In: Organization WH, ed. Geneva; 2002. Disclosure of Interests None declared

Background:The COVID-19 pandemic requires measures to reduce patient exposure to the risk of contamination, in particular by limiting hospital admissions and promoting lockdown. In order to respond to these healthcare measures, patients were offered to replace intravenous infusions (IV) of abatacept (ABT) and tocilizumab (TCZ) to subcutaneous injections (SC).Objectives:To assess the outcome of patients who switched from IV ABT or TCZ to SC during the COVID-19 pandemic.Methods:A survey was conducted in December 2020 in partnership with the national AFP-RIC patient association to assess the outcome and satisfaction of patients who switched from ABT or TCZ IV to SC during the first wave of COVID-19 pandemic.We also analysed the outcome of patients who switched from IV ABT or TCZ to SC in the rheumatology department of Cochin Hospital during the lockdown in April/may 2020. Articular activity parameters (swollen joint count, pain joint count, visual analogic pain scale, CRP, DAS-28 activity score) were assessed at medical visits before and 6 months after switching from IV to SC.The data collected from the AFP-RIC patient association and the rheumatology department of Cochin Hospital were then aggregated and analyzed by Chi-square and Wilcoxon tests.Results:81 patients responded to the survey carried out by AFP-RIC patient association, including 29 treated with IV ABT (n=15, 52%) or TCZ (n=14, 48%). 17/29 (59%) were offered to switch from IV to SC, 14/17 patients (82%) accepted and 7 patients were still receiving ABT or TCZ SC injections in December 2020. In the rheumatology department of Cochin hospital, 71 patients were scheduled in April/May 2020 to receive IV ABT or TCZ, and 27 (38%) switched to SC. After 6 months, 19 patients (70%) had maintained SC injections, were satisfied with this injection route of administration and their articular activity parameters were unchanged (Table 1).Table 1.Course of Disease parameters evaluated in the 19 patients who maintained abatacept or tocilizumab SC injections in the Rheumatology department of Cochin HospitalParameter, mean(SD)Inclusion visitSwitch to SC(n=19)6 month visit (n=19)P-valueDAS282.3 (1.2)2.3 (0.7)0.62Tender joint count2.5 (3.5)1.3 (1.7)0.49Swollen joint count1.3 (2.5)0.9 (0.6)0.35Patient Global Health (cm)3.2 (1.9)2.6 (1.8)0.60CRP (mg/L)3.2 (4.1)5.2 (4.9)0.56CRP: C-Reactive Protein, SD: Standard DeviationThe combined analysis of these two populations included 41 patients (33 rheumatoid arthritis, RA, 7 juvenile idiopathic arthritis, JIA and 1 polymyalgia rheumatica) who switched to SC ABT or TCZ. 26/41 (63.5%) patients maintained SC injections and IV was re-established in 15/41 (36.5%). Reasons for returning to IV were poor tolerance of SC injections (n=6, 40%), worsening symptoms (n=11, 73%), patient preference to see a rheumatologist in hospital (n=10, 67%) and the high number of SC injections (n=2, 13%). The proportion of patients returning to IV was higher in RA patients compared to patients with JIA (42% vs. 14%, p = 0.08). Age and disease duration were not significantly different between patients who maintained SC injections and those who returned to IV (respectively p=0.97 and p=0.63).Conclusion:Our study suggests that switching from IV ABT or TCZ to SC is an acceptable procedure during the COVID-19 pandemic, especially for patients with JIA.Acknowledgements:Association AFP-RIC (Angélique Hochedé, Cyrielle Beller, Sandrine Rollot) and the members of the association for their help in the conduction of the surveyDisclosure of Interests:None declared.

Importance Osteopathic manipulative treatment (OMT) is frequently offered to people with nonspecific low back pain (LBP) but never compared with sham OMT for reducing LBP-specific activity limitations. Objective To compare the efficacy of standard OMT vs sham OMT for reducing LBP-specific activity limitations at 3 months in persons with nonspecific subacute or chronic LBP. Design, setting, and participants This prospective, parallel-group, single-blind, single-center, sham-controlled randomized clinical trial recruited participants with nonspecific subacute or chronic LBP from a tertiary care center in France starting February 17, 2014, with follow-up completed on October 23, 2017. Participants were randomly allocated to interventions in a 1:1 ratio. Data were analyzed from March 22, 2018, to December 5, 2018. Interventions Six sessions (1 every 2 weeks) of standard OMT or sham OMT delivered by nonphysician, nonphysiotherapist osteopathic practitioners. Main outcomes and measures The primary end point was mean reduction in LBP-specific activity limitations at 3 months as measured by the self-administered Quebec Back Pain Disability Index (score range, 0-100). Secondary outcomes were mean reduction in LBP-specific activity limitations; mean changes in pain and health-related quality of life; number and duration of sick leaves, as well as number of LBP episodes at 12 months; and consumption of analgesics and nonsteroidal anti-inflammatory drugs at 3 and 12 months. Adverse events were self-reported at 3, 6, and 12 months. Results Overall, 200 participants were randomly allocated to standard OMT and 200 to sham OMT, with 197 analyzed in each group; the median (range) age at inclusion was 49.8 (40.7-55.8) years, 235 of 394 (59.6%) participants were women, and 359 of 393 (91.3%) were currently working. The mean (SD) duration of the current LBP episode was 7.5 (14.2) months. Overall, 164 (83.2%) patients in the standard OMT group and 159 (80.7%) patients in the sham OMT group had the primary outcome data available at 3 months. The mean (SD) Quebec Back Pain Disability Index scores for the standard OMT group were 31.5 (14.1) at baseline and 25.3 (15.3) at 3 months, and in the sham OMT group were 27.2 (14.8) at baseline and 26.1 (15.1) at 3 months. The mean reduction in LBP-specific activity limitations at 3 months was -4.7 (95% CI, -6.6 to -2.8) and -1.3 (95% CI, -3.3 to 0.6) for the standard OMT and sham OMT groups, respectively (mean difference, -3.4; 95% CI, -6.0 to -0.7; P = .01). At 12 months, the mean difference in mean reduction in LBP-specific activity limitations was -4.3 (95% CI, -7.6 to -1.0; P = .01), and at 3 and 12 months, the mean difference in mean reduction in pain was -1.0 (95% CI, -5.5 to 3.5; P = .66) and -2.0 (95% CI, -7.2 to 3.3; P = .47), respectively. There were no statistically significant differences in other secondary outcomes. Four and 8 serious adverse events were self-reported in the standard OMT and sham OMT groups, respectively, though none was considered related to OMT. Conclusions and relevance In this randomized clinical trial of patients with nonspecific subacute or chronic LBP, standard OMT had a small effect on LBP-specific activity limitations vs sham OMT. However, the clinical relevance of this effect is questionable. Trial registration ClinicalTrials.gov Identifier: NCT02034864.

Objectives: We aim to evaluate the benefits and harms of intervertebral disc therapies (IDTs) in people with non-specific chronic low back pain (NScLBP). Methods: We conducted a systematic review and meta-analysis of randomized trials of IDTs versus placebo interventions, active comparators or usual care. EMBASE, MEDLINE, CENTRAL and CINHAL databases and conference abstracts were searched from inception to June 2020. Two independent investigators extracted data. The primary outcome was LBP intensity at short term (1 week–3 months), intermediate term (3–6 months) and long term (after 6 months). Results: Of 18 eligible trials (among 1396 citations), five assessed glucocorticoids (GCs) IDTs and were included in a quantitative synthesis; 13 assessed other products including etanercept ( n = 2), tocilizumab ( n = 1), methylene blue ( n = 2), ozone ( n = 2), chymopapaine ( n = 1), glycerol ( n = 1), stem cells ( n = 1), platelet-rich plasma ( n = 1) and recombinant human growth and differentiation factor-5 ( n = 2), and were included in a narrative synthesis. Standardized mean differences (95% CI) for GC IDTs for LBP intensity and activity limitations were −1.33 (−2.34; −0.32) and −0.76 (−1.85; 0.34) at short term, −2.22 (−5.34; 0.90) and −1.60 (−3.51; 0.32) at intermediate term and −1.11 (−2.91; 0.70) and −0.63 (−1.68; 0.42) at long term, respectively. Odds ratios (95% CI) for serious and minor adverse events with GC IDTs were 1.09 (0.25; 4.65) and 0.97 (0.49; 1.91). Conclusion: GC IDTs are associated with a reduction in LBP intensity at short term in people with NScLBP. Positive effects are not sustained. IDTs have no effect on activity limitations. Our conclusions are limited by high heterogeneity and a limited methodological quality across studies. Registration PROSPERO: CRD42019106336.

Introduction/Background Active disc disease is characterized by inflammatory-like low back pain (LBP) and the presence of Modic 1 changes on MRI. Its prevalence ranges from 19% to 50% in patients with nonspecific chronic LBP. Pelvic parameters are important determinants of shear and compressive forces applied to the lumbar intervertebral disc. The association between an active disc disease and abnormal pelvic parameters has not been addressed yet. We aimed to compare pelvic parameters between chronic LBP patients with an active disc disease (Modic 1) and those without (Modic 0). Material and method We used a convenient sample from patients prospectively and consecutively recruited in a previous single center case-control pilot study. Cases were defined as chronic LBP male patients with an active disc disease on MRI and controls as patients without. Pelvic parameters, namely sacral slope, pelvic tilt and pelvic incidence, were assessed in an independent and standardized manner by two trained investigators using EOS system imaging performed at inclusion. Results Overall, 35 cLBP patients (13 cases and 22 controls) fulfilled inclusion criteria and had an EOS imaging available. Median age was 42 (35–51.5) years and median LBP duration 50 (33.5–104) months. Pelvic parameters did not differ between the 2 groups: absolute mean (95% IC) difference between Modic 0 and Modic 1 was −7.2° (−15.5; 1.0) for pelvic incidence, −3.7° (−8.7; 1.3) for pelvic tilt and −3.3 (−8.9; 2.3) for sacral slope. Conclusion Pelvic parameters in patients with chronic LBP and an active disc disease do not differ from those in patients without.

In the late 1980s, the description by Modic and colleagues of elementary discovertebral changes detected on MRI (Modic classification) suggested for the first time a possible correlation between anatomical and clinical features in a subgroup of patients with non-specific chronic low back pain. Degenerative disc disease is frequent and usually asymptomatic, but Modic 1 changes in the vertebral endplates adjacent to a degenerated disc are associated with inflammatory-like chronic low back pain and low-grade local and systemic inflammation, which led to the concept of ‘active discopathy’. Active discopathy shares some similarities with acute flares of peripheral osteoarthritis. Likewise, what triggers disc activation and how it self-limits remain unknown. A better understanding of mechanisms underlying disc activation and its self-limitation is of clinical relevance because it may enable the design of more targeted pharmacological and non-pharmacological interventions for the subgroup of patients with chronic low back pain and active discopathy. Here, we narratively review current disc-centred biomechanical and biochemical hypotheses of disc activation and discuss evidence of interactions with adverse personal and environmental factors.