Grégoire Cormier

Non–TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial

Importance One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α (TNF-α) inhibitors; little guidance on choosing the next treatment exists. Objective To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor. Design, Setting, and Participants A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR]  ≥ 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013. Interventions Patients were randomly assigned (1:1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician. Main Outcomes and Measures The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 ≤3.2), remission (DAS28 ≤2.6); serious adverse events; and serious infections. Results Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003). Conclusions and Relevance Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication. Trial Registration clinicaltrials.gov Identifier: NCT01000441.

Septic arthritis of the facet joint

OBJECTIVE Septic arthritis of the facet joint is a rare clinical entity. We report 11 cases of facet joint infections diagnosed in our institution. PATIENTS AND METHOD Patients were identified via the computerized patients record (PMSI). Their features were collected and compared with published data. RESULTS The clinical symptoms are similar to those of infectious spondylodiscitis: back pain with stiffness (11/11), fever (9/11), radicular pain (5/11), and asthenia. Ten patients presented with lumbar infection and 1 with dorsal infection. An inflammatory syndrome was observed in every case. A rapid access to spine MRI allowed making the diagnosis in every case, and assessing a potential extension of infection (epidural extension 5/11, paraspinal extension 5/11). Blood culture (8/11) or culture of spinal samples allowed identifying the causative bacterium in every case and adapting the antibiotic treatment. The bacteria identified in our series were different from previously reported ones, with less staphylococci. The origin of the infection was found in 4 cases. Another localization of infection was observed in 4 cases. The outcome was favorable with medical treatment in 10 cases. An abscess was surgically drained in 1 case. None of our patients presented with neurological complications, probably because of the rapid diagnosis. CONCLUSION Assessing the facet joint is essential in case of inflammatory back pain, and the radiologist must be asked to perform this examination.

Chronic, eventually fatal, Kawasaki-like disease in an adult with spondylarthropathy responding to IVIG therapy.

Abstract We report on an unusual case of a 40-year-old Caucasian male displaying severe Kawasaki-like symptoms. The disease lasted for seven years before diffuse coronary aneurysms occurred, leading to the patients death, despite ongoing treatment by intravenous immunoglobulins (IVIGs). The patient had also been suffering from a disabling inflammation of the spine, which was reported to have started at the onset of the disorder. Whereas neither NSAIDS, nor high doses corticosteroids, or anti-TNF drugs had a clear effect, the clinical features of spinal inflammation were highly sensitive to IVIGs, and were attributed definitively to HLA-B27-negative axial spondylarthropathy after bone scan and magnetic resonance imaging disclosed typical enthesitis of both heels and bilateral sacroiliitis.

Does immunodepression induced by TNF antagonists promote atypical scabies

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 14 aout 2013

Vitamin D insufficiency: evaluation of an oral standardized supplementation using 100,000 IU vials of cholecalciferol, depending on initial serum level of 25OH vitamin D.

OBJECTIVES There is no protocol of vitamin D supplementation used worldwide due to a great disparity of vitamin D supplements available in different countries. The aim of this study was to evaluate the efficiency of the protocol most often used in France to correct vitamin D deficiency defined by a serum 25-hydroxy vitamin D (25OHD) level of less than 30 ng/mL. METHODS This was a pragmatic multicentric study of vitamin D supplementation in 257 osteopenic/osteoporotic, vitamin D deficient patients who received 100,000 UI vitamin D3 vials every two weeks according to their initial serum 25OHD level (four vials when 25OHD less than 10 ng/mL, three when 25OHD was 10-19 ng/mL, two when 25OHD was 20-29 ng/mL). Blood samples were obtained at baseline, one (M1), two (M2), and three months (M3), after the end of the supplementation protocol. RESULTS At M1, 198/257 (77%) patients had a serum 25OHD level more than 30 ng/mL. Eighty-five percent of those with a BMI less than 25 kg/m2 had a 25OHD concentration more than 30 ng/mL, whereas only 66% of those with a BMI more than 25 had a level more than 30 ng/mL. At M2 and M3, 25OHD levels decreased significantly with 55% and 46% having still a level more than 30 ng/mL respectively, without any significant difference according to the initial 25OHD level. CONCLUSION This protocol was effective in rising serum 25OHD of most vitamin D insufficient patients with a BMI less than 25 kg/m2, but not in overweight patients. As almost one half of our patients had a serum 25OHD level less than 30 ng/mL at M2, we suggest that regular doses should be started quite soon after this initial supplementation.

Sciatica with motor loss and hemi-cauda equina syndrome due to varicella-zoster virus meningoradiculitis.

Joint Bone Spine - In Press.Proof corrected by the author Available online since vendredi 1 mars 2013

Hairy-cell leukemia with inaugural joint manifestations

Hairy-cell leukemia is a chronic B-cell malignancy seen in adults. The presenting manifestations consist of splenomegaly, pancytopenia, and characteristic monocyte depletion. The presence in peripheral blood or bone marrow of hairy cells exhibiting the CD19(+) CD20(+) CD25(+) CD11c(+) phenotype establishes the diagnosis. Rarely, patients present with inaugural joint manifestations related either to the hematological malignancy or to immune dysfunction. The resulting polymorphic polyarticular symptoms may cause diagnostic wanderings. Monocytopenia is a valuable diagnostic clue. The identification of hairy cells in the joint fluid establishes the diagnosis of leukemia-related arthritis. The treatment rests on purine analogs. One of the main differential diagnoses is Feltys syndrome, which combines rheumatoid arthritis, splenomegaly, and neutropenia. Feltys syndrome is usually caused by T-cell lymphoproliferative disorders. Among 27 patients with hairy-cell leukemia managed at our institution, 1 presented with joint manifestations. We describe this case.

Ultrasound abnormalities in septic arthritis are associated with functional outcomes

OBJECTIVES To describe the ultrasound abnormalities seen in septic arthritis and to assess their associations with clinical, biological, and radiological outcomes. METHODS We prospectively included 34 patients with septic arthritis of a native joint (knee, n=19; shoulder, n=6; hip, n=4; ankle, n=3; or wrist, n=2). Ultrasonography was performed to record synovial-membrane thickness and vascularity, joint effusion, and abnormalities of adjacent soft tissues, at baseline then 4days, 2weeks, and 3months later. Motion-range limitation of the affected joint was evaluated after 3months. Radiography was performed at inclusion and after 3months. RESULTS Mean age was 63.7±17.6years. After 3months, 20 (58.8%) patients had motion-range limitation with worsening of the total radiological score (P<0.001). The proportion of patients with synovitis was very high initially (96.4% at baseline, 96.3% after 4days, and 100% after 2weeks) then diminished to 77.8% after 3months (P=0.051). Synovial-membrane thickness was significantly higher after 4days and 2weeks compared to baseline (median, +17.3% and +20%, respectively; P=0.015) and was significantly lower after 3months compared to the earlier time points (median, -31.5%, P=0.015). A positive Doppler signal was common at baseline (n=18, 64.3%) then significantly less so after 3months (n=7, 25.9%; P=0.04). An unchanged or higher Doppler grade after 2weeks compared to baseline was associated with motion-range limitation at last follow-up (P=0.033). CONCLUSION We report the first study on ultrasound evidence of synovitis, joint effusion, and soft tissue alterations at baseline and over time in patients with septic arthritis. Persistent synovitis and joint effusion 3months after starting antibiotic therapy was not associated with treatment failure. However, Doppler signal changes over the first 2weeks were associated with the 3-month functional outcome.

Arthrites septiques à Staphylococcus caprae

Staphylococcus caprae est un staphylocoque coagulase négaive mis en évidence pour la première fois chez l’homme en 1991 1]. Il est associé à des infections ostéoarticulaires [2,3], des bacériémies [4,5], des infections urinaires [4], une endocardite [4] t une méningite [6]. Nous rapportons deux cas d’infection articulaire à S. caprae : ne sacro-iliite et une arthrite de genou sur prothèse totale.

Ultrasound characterization of ankle involvement in Löfgren syndrome

BACKGROUND Bilateral ankle arthritis is a classic diagnostic criterion for Löfgren syndrome. The objective of this study was to use ultrasonography to characterize the articular and periarticular involvement of the ankles in patients with Löfgren syndrome. METHODS Multicenter descriptive cohort study of patients with Löfgren syndrome who underwent ultrasonography of the ankles. We collected clinical data, imaging study findings, blood test results, and joint fluid properties in patients who underwent joint aspiration. RESULTS Findings from ultrasonography of the ankles in 40 patients were analyzed. The most common B-mode abnormality was subcutaneous edema (26/40), followed by tenosynovitis (22/40), with no differences in frequency across compartments. Joint involvement manifested as synovitis in 7 patients and effusion in 10 patients. Synovitis with increased vascularity by power Doppler was found in 3 patients. No statistically significant associations were found linking synovitis or tenosynovitis to clinical features (age and gender), laboratory tests, or imaging study findings. CONCLUSION Contrary to the classical view, our results indicate that ankle involvement in Löfgren syndrome is more often abarticular than articular. The inclusion of bilateral ankle arthritis among the diagnostic criteria for Löfgren syndrome deserves reappraisal.