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Objective: To develop and validate a patient knowledge questionnaire regarding axial spondyloarthritis (axSpA)., Methods: Knowledge considered essential for patients with axSpA was identified through Delphi rounds among rheumatologists, healthcare professionals (HCPs), and patients, then reformulated to develop the knowledge questionnaire. Cross-sectional validation was performed in 14 rheumatology departments to assess internal validity (Kuder-Richardson coefficient), external validity, acceptability, reproducibility (Lin concordance correlation coefficient), and sensitivity to change (knowledge score before vs after patient education sessions and effect size)., Results: The Spondyloarthritis Knowledge Questionnaire (SPAKE) is a self-administered 42-item questionnaire with a 32-item short form, both scored 0 to 100, assessing knowledge of disease, comorbidities, pharmacological treatments, nonpharmacological treatments, self-care, and adaptive skills. In the validation study (130 patients; 67 [51.5%] male, mean age 43.5 [SD 12.9] yrs), the mean (SD) score of the long-form questionnaire was 71.6 (15.4), with higher scores (better knowledge) in nonpharmacological treatments and adaptive skills and lower scores in cardiovascular comorbidity and pharmacological treatments. Acceptability was good, with no missing data; the internal validity coefficient was 0.85. Reproducibility was good (0.81, 95% CI 0.72-0.89). SPAKE showed good sensitivity to change; scores were 69.2 (15.3) then 82.7 (14.0) after patient education sessions (Hedges effect size = 0.92, 95% CI 0.52-1.31)., Conclusion: SPAKE is a knowledge questionnaire for patients with axSpA, developed with the involvement of HCPs and patients and reflecting current recommendations for the management of axSpA. SPAKE will be useful in assessing knowledge acquisition and self-management strategies in routine care and research., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: Inflammatory bowel disease (IBD) is a well-known extraarticular feature of spondyloarthritis (SpA). The aims of this study were to evaluate factors associated with IBD and incidence over 5 years of followup in the DESIR cohort., Methods: DESIR is a prospective observational cohort of patients with recent-onset inflammatory back pain suggestive of axial SpA. All available variables in the database were compared between patients with and without IBD at baseline and 5 years, and occurrence over 5 years of followup, with uni- and then multivariable analysis., Results: At baseline, of 708 patients, 35 had IBD (prevalence 4.94%, CI 95% 3.3-6.5). IBD was associated (multivariable) with history of uveitis, levels of Dickkopf-1, and tumor necrosis factor, but not with phenotypic presentation (peripheral arthritis, enthesitis, dactylitis, uveitis) or baseline serum levels of other cytokines. At 5 years, 480 patients were analyzed, 58 with IBD. IBD was associated (multivariable) with fulfillment of modified New York criteria, sick leave, Bath Ankylosing Spondylitis Disease Activity Index, and smoking. There was no association with magnetic resonance imaging scores, enthesitis, psoriasis, and bone mineral density. Twenty-three incident cases of IBD were recorded: estimated occurrence rate of 0.95/100 (95% CI 0.57-1.35) patient-years (PY). Incidence of IBD is associated (multivariable) with HLA-B27 (OR 0.36, 95% CI 0.22-0.59), fulfillment of modified New York criteria (OR 3.35, 95% CI 1.85-6.08), and familial history of IBD (OR 3.31, 95% CI 1.62-6.77)., Conclusion: In early SpA, IBD occurs with an incidence of 1/100 PY, and is associated with poor outcome, familial history of IBD, absence of HLA-B27, and fulfillment of modified New York criteria.

Objective: To describe deaths for which ankylosing spondylitis (AS) was on death certificates in France., Methods: Death certificates in which AS was indicated were evaluated. Standard mortality ratio (SMR) was assessed., Results: AS appeared in 2940 death certificates. The mortality rate of AS seemed stable. The most frequent initial causes were diseases of the circulatory system [28.3% in the International Classification of Diseases, 10th ed (ICD-10)]. SMR adjusted for age and sex were 2.1 (95% CI 1.45-2.91) for infections and 0.43 (0.36-0.5) for cancers (ICD-10 period)., Conclusion: This study found an increase in mortality from infectious and external causes of death; conversely, patients with AS appear to die less frequently from cancer.

Objective: To assess the relationship between the body mass index (BMI) and the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA)., Methods: We conducted a retrospective study in 222 patients with RA followed by 5 centers. The European League Against Rheumatism response was evaluated at 6 months. Univariate and multivariate logistic regressions were performed., Results: No significant association between the BMI and the response to TCZ at 6 months was found after adjustment for potential confounding factors (adjusted OR 0.45, 95% CI 0.16-1.24, p = 0.13 and OR 1.19, 95% CI 0.31-4.48, p = 0.78 for BMI 25-30 kg/m(2) and BMI > 30 kg/m(2), respectively, compared to BMI < 25 kg/m(2))., Conclusion: Response to TCZ in patients with RA is not influenced by the baseline BMI, in contrast to anti-tumor necrosis factor drugs.

Objective: To determine the prevalence and type of ultrasonographic (US) lesions of the anterior chest wall (ACW) in cases of spondyloarthritis (SpA)., Methods: This monocentric, prospective, and controlled study included patients consulting for SpA (Assessment of Spondyloarthritis International Society criteria) and control subjects. Clinical (pain and swelling) and US assessments (synovitis, joint effusion, erosion, ankylosis, margin narrowing, or Doppler signal) were performed on the sternoclavicular (SCJ) and the manubriosternal (MSJ) joints. The main characteristics of SpA were recorded [disease duration, biologic features, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), radiographic and extraarticular involvement]., Results: The study included 131 patients with SpA and 49 control subjects (same age and sex ratio). Clinical and US involvement of ACW were found in, respectively, 39% and 35.5% of SpA and in 12% and 14.3% of controls (p < 0.01). US highlighted erosions (34 vs 0), margin narrowing (12 vs 0), power Doppler activity (18 vs 2; p < 0.05), and ankylosis of the MSJ (24 vs 3). US involvement was associated with disease duration (14.9 vs 11.1 years; p = 0.04), age (45 vs 41 years; p = 0.004), radiographic change of sacroiliac joint (p = 0.05), and presence of inflammatory bowel disease (IBD; p = 0.03). No associations were found with HLA-B27, psoriasis, enthesitis, uveitis, or clinical involvement of ACW. Clinical involvement is associated with a higher BASDAI (47 vs 32; p = 0.0009) and ASDAS (2.9 vs 2.2; p = 0.006)., Conclusion: US involvement of ACW is frequent in SpA (36.5%), mainly with erosion of SCJ and ankylosis of MSJ. It is associated with disease duration, radiographic sacroiliitis, and IBD.

Objective: To determine the prevalence and characterize the inflammatory musculoskeletal symptoms of hidradenitis suppurativa (HS), a chronic inflammatory disease of skin appendages., Methods: Patients with HS referred to 3 dermatology university hospital centers were systematically screened for peripheral arthritis, dactylitis, inflammatory back pain, or enthesitis. After careful clinical examination, patients were further classified according to clinical and imaging criteria for spondyloarthritis (SpA) using the Amor, European Spondyloarthropathy Study Group (ESSG), and ASsessment in ankylosing spondylitis (ASAS)., Results: We screened 640 patients with HS; 184 had musculoskeletal symptoms. In all, 43 (mean age 39.4 yrs, ± 8.3; 80% women) had arthritis, inflammatory back pain, or enthesitis and were investigated further. Signs of HS preceded the onset of articular symptoms in 39 patients (90%), at a mean interval of 3.6 years. A total of 18 (41%), 24 (55%), and 15 (34%) patients fulfilled the Amor, ESSG, and ASAS criteria, respectively, while synovitis, acne, pustolosis, hyperostosis, and osteitis (SAPHO) syndrome was established in 4 patients. The crude prevalence of SpA in all 640 patients with HS was 3.7% by the ESSG criteria., Conclusion: SpA may occur in patients with HS, with the prevalence in this group exceeding that in the general population. The very short time between skin and joint symptom onset in some cases suggests common pathogenic mechanisms underlying HS and SpA.

Objective: To determine the prevalence of anterior chest wall (ACW) pain in patients with recent inflammatory back pain (IBP) suggestive of spondyloarthritis (SpA), and to investigate the influence of ACW pain on the overall features of these patients., Methods: The DESIR cohort is a prospective, multicenter French cohort of patients with early IBP suggestive of SpA, including 708 patients (mean age 33.8 yrs, 53.8% females, 57.3% HLA-B27-positive). ACW pain was defined by at least 1 episode of chest wall pain attributed to SpA by the rheumatologist, after ruling out other causes of chest pain. Data on the baseline demographic characteristics, functional status and quality of life, imaging features, bone mineral density, and blood tests were compared in patients with and those without ACW pain. Factors associated with ACW pain were identified by univariate and multivariate analysis (logistic regression)., Results: The prevalence of ACW pain in the DESIR cohort (n = 316/708 patients) was 44.6% (95% CI 40.9-48.3). ACW pain occurred after the first symptoms of IBP in 62%. Localization was diffuse in 41% of the positive cases. A stepwise multivariate analysis found an association between ACW pain and the enthesitis score, involvement of thoracic spine, diagnosis of ankylosing spondylitis (AS), and radiographic abnormalities of sacroiliac joints., Conclusion: In recent IBP suggestive of SpA, presence of ACW pain is associated with enthesitis, thoracic spine involvement, radiographic sacroiliitis, diagnosis of AS, and with a more severe disease. ACW pain could be interpreted as a diagnostic feature for AS.

Objective: To evaluate the efficacy and safety of rituximab (RTX) in several subsets of spondyloarthritis (SpA) using the data of the AIR (Autoimmunity and Rituximab) registry., Methods: All patients receiving RTX for SpA, and prospectively included in the AIR registry from September 2005 to September 2010, were retrospectively analyzed. The response to treatment was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index for axial disease, joint count for peripheral disease, and C-reactive protein reduction., Results: Among the 595 patients included in the AIR registry, 26 patients with SpA from 13 centers were reported: ankylosing spondylitis (10), undifferentiated SpA (7), and psoriatic arthritis (9). Mean disease duration was 8.8 years (range 1-40). The extraarticular features found were psoriasis, 12 cases; uveitis, 4 cases; and Crohn's disease, 3 cases. The mean number of disease-modifying antirheumatic drugs before RTX was 2.4; previous anti-tumor necrosis factor (TNF) agents were taken in 23 cases. The mean number of RTX courses was 1.5 (range 1-5), with a total of 35.6 patient-years. Efficacy was noted in 11/23 cases: 3 out of 3 anti-TNF-naive patients and 8 out of 20 anti-TNF nonresponder patients. No predictive factors of response could be identified, particularly in diagnosis subsets or clinical presentation (axial or peripheral)., Conclusion: In this nationwide study of several subsets of SpA, RTX had only a moderate efficacy that was more marked in patients who were anti-TNF-naive.

Objective: To describe 3 cases of scleritis associated with etanercept use for rheumatoid arthritis (RA) and to review the literature related to inflammatory eye diseases associated with the use of etanercept., Methods: Three cases of severe scleritis during etanercept therapy were analyzed. A systematic review of the literature in PubMed, Embase, and the Cochrane Library was performed, from 1962 to July 2010., Results: Three patients with seropositive RA developed scleritis 7-28 months after initiation of etanercept, for the first time during their long-lasting disease. In all patients the underlying disease had responded well to anti-tumor necrosis factor therapy. Ocular inflammation went into remission after discontinuation of etanercept, and no other relapses were observed. One patient experienced a dechallenge-rechallenge phenomenon (improvement in symptoms following discontinuation of the agent, then reappearance or worsening of symptoms on reexposure to the agent). Forty-two cases of inflammatory eye diseases believed to be associated with the use of etanercept have been reported in the literature: 33 uveitis, 8 scleritis, 1 orbital myositis, concerning 16 patients with RA, 10 with juvenile idiopathic arthritis, 14 with ankylosing spondylitis, and 2 with psoriatic spondyloarthropathy. Dechallenge was performed in 28 patients, leading to resolution of symptoms. Rechallenge was done in 6 cases, with clear exacerbation., Conclusion: Ocular inflammation is paradoxically a potential adverse effect of etanercept, even in previously uninvolved eyes.

Objective: To describe cases of development of pulmonary nodulosis or aseptic granulomatous lung disease in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor-alpha (TNF-alpha) therapy., Methods: A call for observation of such cases was sent to members of the French "Club Rhumatismes et Inflammation." The cases had to occur after introduction of TNF-alpha-blocking therapy., Results: Eleven cases were examined: 6 patients were treated with etanercept, 2 with infliximab, and 3 with adalimumab. Pulmonary nodular lesions were observed after a mean treatment period of 23.3 +/- 15.3 months. Clinical symptoms were observed in 5 cases. Radiographs or computed tomography of the chest showed single or multiple nodular lesions in 10 cases and hilar adenopathies in 1 case. Biopsy of the nodular chest lesions or mediastinal lymphadenopathies were performed in 8 patients, and revealed typical rheumatoid nodules in 4 cases and noncaseating granulomatous lesions in 4 cases. Mycobacterial or opportunistic infections were excluded for all cases. Outcome was favorable for all the patients, with either discontinuation or maintenance of anti-TNF-alpha treatment., Conclusion: Aseptic pulmonary nodular inflammation corresponding to rheumatoid nodules or noncaseating granulomatous inflammation can occur during anti-TNF-alpha therapy for RA, mainly etanercept. The mechanism explaining such a reaction is not clear but certainly includes different processes. These cases of pulmonary nodular inflammation generally have a benign course and do not systematically require withdrawal of treatment.

Objective: Rheumatoid arthritis (RA) is a disease characterized by prolonged production of tumor necrosis factor-alpha (TNF-alpha), which is regulated by the Rel/nuclear factor-kappaB (NF-kappaB) transcription factors. We assessed NF-kappaB activation in peripheral blood mononuclear cells (PBMC), peripheral blood lymphocytes (PBL), and monocytes from patients with RA, patients with ankylosing spondylitis (AS), and healthy subjects., Methods: NF-kappaB activation was determined by electrophoretic mobility shift assays and by Western blotting in PBMC, monocytes, and PBL isolated from peripheral blood of patients with RA, patients with AS, and healthy subjects and determined after ex vivo pretreatment of PBMC, PBL, and monocytes of patients with RA and healthy subjects with infliximab and with etanercept., Results: Enhanced NF-kappaB activation was observed in monocytes, PBL, and PBMC isolated from patients with RA, but not in PBMC, PBL, and monocytes of patients with AS and healthy subjects. The NF-kappaB complex was composed of p50 and p65 subunits and its activation required inhibitor of NF-kappaBalpha degradation. We observed a positive correlation between the NF-kappaB activation in monocytes, PBL, and PBMC, and TNF-alpha levels in peripheral blood of patients with RA. Ex vivo treatment with infliximab and etanercept decreased NF-kappaB activation in monocytes of patients with RA, but not in PBL and PBMC, and not in healthy subjects., Conclusion: Our results indicate a role for NF-kappaB activation and TNF-alpha in the activation of monocytes of patients with RA, and suggest an important role of circulating monocytes in RA pathogenesis.

Objective: To determine whether hepatitis C virus (HCV) RNA could be detected in the salivary glands of patients with both a diagnosis of Sjögren's syndrome (SS) and HCV infection., Methods: Five patients with primary SS (European criteria) and chronically infected by HCV and 3 controls (one with primary SS without HCV infection, another with HCV infection without sicca syndrome, and a third without SS and HCV infection) were tested for the presence of HCV-RNA (using reverse transcriptase-polymerase chain reaction) in their saliva, serum, and salivary glands., Results: In the patient group, HCV-RNA was detected in the serum and saliva of all cases and RNA extracted from salivary gland specimens tested positive in 3 cases. In the control group, HCV-RNA was not detected in the serum, saliva, or salivary glands from subjects without HCV infection. Only the control subject with HCV but without sicca syndrome tested positive for the presence of HCV-RNA in the serum, saliva, and salivary gland tissue., Conclusion: Our results showed that HCV may propagate and reside within salivary gland tissue, leading to HCV associated sialadenitis or Sjögren's-like syndrome in some cases, a phenomenon that does not seem specific. However, a direct role for HCV in the physiopathology of certain cases of primary SS is suggested.

Objective: To examine the effects of HLA-DRB1 alleles and amino acid sequences that carry the shared epitope (SE) upon rheumatoid arthritis (RA) susceptibility and disease severity in patients from Eastern France., Methods: HLA-DRB1 alleles were determined in 120 patients and 104 healthy controls by polymerase chain reaction/sequence specific oligonucleotide probes. Subtyping of DRB1*01 and *04 were performed using sequence specific primers. Patients were retrospectively evaluated for disease duration, age at disease onset, presence of rheumatoid factors, subcutaneous nodules, vasculitis and other extraarticular diseases, for the need for arthroplasty and immunosuppressive/immunoregulatory agents, and for radiographic damage., Results: The prevalence of HLA-DRB1*04 was significantly higher in patients (46.6%) than in controls (17.3%) (Pcorr = 0.000003). HLA-DRB1*0101 and *0401 were the most prominently associated subtypes in patients with RA (33.3%, Pcorr = 0.011, and 28.3%, Pcorr = 0.00008, respectively). A significant fraction of patients (72.5%) expressed one or 2 copies of the SE (p < 0.0000001; OR 4.77, CI 2.61-8.78). The presence of double SE was associated with a higher risk of developing RA (OR 4.83, CI 1.91-12.71; p = 0.0001). No significant differences in the clinical records among patients expressing no RA linked alleles, one and 2 copies of the SE, were observed. However, analyzing the specific effect of each amino acid sequence, we observed a significant association of the QKRAA motif with vasculitis (p = 0.03) and history of joint replacement surgery (p = 0.05), suggesting a role for lysine in position 71 of the shared sequence., Conclusion: These findings differ from those of previous HLA-DRB1 allele studies in patients with RA from other regions of France. Thus, the heterogeneity in both the expression of DRB1 alleles and the association of these alleles with disease severity could be relevant within a country such as France.

Objective: To identify risk factors associated with disease activity, in a group of patients with spondyloarthropathy (SpA) living in France., Methods: Patients fulfilling the ESSG or Amor criteria for SpA were enrolled in a cross sectional multicenter study. Disease activity was assessed using a French version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Univariate and multivariate analyses were used to identify a link between BASDAI and disease characteristics, genetic factors, and environmental factors such as infectious events, mental stress, working conditions, and dietary factors., Results: We studied 293 patients. On multivariate analysis, BASDAI appeared to be mainly linked to disease duration (negative correlation), the absence of sacroiliitis, and the "frequency of meals taken out of home" (negative correlation)., Conclusion: Disease activity in a French population of patients with SpA appeared to be linked mainly to a shorter disease duration and a peripheral pattern of arthritis, as well as to dietary habits. The underlying links between this last environmental factor and disease activity remained hypothetical and could only reflect a nontested social factor.

Objective: To assess safety and efficacy of a murine anti-CD4 monoclonal antibody (Mab) in a population of patients with rheumatoid arthritis (RA) compared to treatment with placebo., Methods: Fifty-eight patients with defined RA were included in this placebo controlled, randomized, double blind, multicenter study. Of the 48 women and 10 men (mean age 54.5 years), 25 were functional class II and 31 were class III, with 9 years' disease duration; the mean of previous disease modifying antirheumatic drugs was 4; 49 were taking steroids (mean dosage 11 mg/day of prednisone). Eighty percent were rheumatoid factor positive. All were in an active state of the disease with: pain > 4 (mean at inclusion 6.6), tender joints > 4 (mean 12), swollen joint count > 3 (mean 9), morning stiffness > 45 min (mean 185), erythrocyte sedimentation rate > 30 mm (mean 59) or C-reactive protein (CRP) > 30 mg/l (mean 63). Treatment was randomized between murine anti-CD4 Mab (B-F5, Diaclone, 20 mg/day) or placebo intravenously for 10 consecutive days. Efficacy was assessed with a composite index (Paulus), with evaluation of number of patients with 20 or 50% improvement in each group. Changes in measures of single clinical or biological variables were also evaluated., Results: The 2 groups were comparable at inclusion. Treatment was well tolerated. Mild side effects (chills, fever, rash) were seen in both groups. Percentage of patients with global 20 or 50% response did not differ between placebo and Mab groups at Day 10 or at Day 30. Evaluation of single variables showed reduced CRP, swollen joint count, and Ritchie index in some B-F5 patients at Day 10, although in the B-F5 group as a whole only CRP was significant., Conclusion: No significant improvement in RA after murine anti-CD4 Mab was observed.

Objective: To develop a French version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and to determine its metric properties in patients with all forms of spondyloarthropathies (SpA)., Methods: A French version of BASDAI was obtained after a translation and back-translation process. Patients fulfilling the European Spondylarthropathy Study Group or Amor criteria for SpA were included. BASDAI of Day 0, Day 1, and, when treatment was changed, Day 8, and other clinical and biological disease activity variables were recorded, along with assessment of disease activity by the physician or the patient. Scalability, reproducibility, sensitivity to change, internal consistency and redundancy, and construct validity of the index were assessed., Results: We studied 293 patients. Good scalability, reproducibility, construct, and internal validity were observed for BASDAI. Sensitivity to change could not be assessed., Conclusion: The French version of BASDAI exhibited good metric properties in patients with all forms of SpA, confirming its utility in further clinical research in SpA. However, sensitivity to changes due to drug therapy remains to be assessed.

Objective: To study the association between the B7 cross reactive group (B7, B40) and spondyloarthropathy (SpA), taking into account patients with atypical features., Methods: We studied the main clinical and paraclinical features of 51 patients with rheumatoid arthritis, 55 with SpA, 120 with mechanical diseases, and 160 with inflammatory rheumatism not fulfilling the diagnostic criteria currently used. This descriptive analysis was performed using multiple correspondence factorial analysis to identify subgroups among unclassified patients and select SpA variants. We compared HLA frequencies among these groups versus a control group., Results: We identified a subgroup close to the axial SpA and related to B7 (OR:5.91, p = 0.0008), whereas B40 is related to patients close to the peripheral SpA., Conclusion: B7 is related to axial SpA variants manifested by inflammatory low back pain according to Calin's criteria, with either extraarticular signs or sacroiliitis. Followup of such patients is required to determine whether their disease is a new entity or can be considered SpA.

Interleukin 6 (IL-6) appears to be a potential mediator of inflammation that may contribute to the pathogenesis of joint inflammation in RA. Anti-IL-6 monoclonal antibodies (Mab) may represent a new tool in RA treatment. Five patients with RA, after previous anti-CD4 therapy (B-F5) without antimouse immunization were included in our open pilot study. The anti-IL-6 Mab (B-E8, IgG1) was given intravenously (10 mg/day) for 10 consecutive days in hospital. No side effects were noted. Clinical and biological (C-reactive protein) improvement appeared during the treatment period. However improvement was transitory (mean: 2 months). Unexpectedly serum IL-6 levels increased in 4 patients with this treatment that seemed to have antiinflammatory effects. Further studies are required to evaluate the real benefit and the mode of action of this Mab.

Ten patients with severe rheumatoid arthritis were treated with a murine monoclonal anti-CD4 (B-F5) antibody in an open study (one with 10 mg/day, 2 with 15 mg/day, 7 with 20 mg/day) for 10 consecutive days. Tolerance was excellent. All patients improved during treatment clinically (Ritchie's index, morning stiffness, pain scale) (p = 0.005), as well as biologically C-reactive protein (p = 0.008) with an average 60% reduction of each of these variables at Day 15, and clinical benefit lasted over 6 months in some patients. No significative depletion was noted in total lymphocyte or CD3, CD4, CD8, CD20, positive cells after treatment. Evidence of murine immunization was found in only 2 patients.