Towards the Lowest Efficacious Dose: Results From a Multicenter Noninferiority Randomized Open-Label Controlled Trial Assessing Tocilizumab or Abatacept Injection Spacing in Rheumatoid Arthritis in Remission.

OBJECTIVE: We assess the clinical and structural impact at two years of progressively spacing tocilizumab (TCZ) or abatacept (ABA) injections versus maintenance at full dose in patients with rheumatoid arthritis in sustained remission. METHODS: This multicenter open-label noninferiority (NI) randomized clinical trial included patients with established rheumatoid arthritis in sustained remission receiving ABA or TCZ at a stable dose. Patients were randomized to treatment maintenance (M) at full dose (M-arm) or progressive injection spacing (S) driven by the Disease Activity Score in 28 joints every 3 months up to biologics discontinuation (S-arm). The primary end point was the evolution of disease activity according to the Disease Activity Score in 44 joints during the 2-year follow-up analyzed per protocol with a linear mixed-effects model, evaluated by an NI test based on the one-sided 95% confidence interval (95% CI) of the slope difference (NI margin 0.25). Other end points were flare incidence and structural damage progression. RESULTS: Overall, 202 of the 233 patients included were considered for per protocol analysis (90 in S-arm and 112 in M-arm). At the end of follow-up, 16.2% of the patients in the S-arm could discontinue their biologic disease-modifying antirheumatic drug, 46.9% tapered the dose and 36.9% returned to a full dose. NI was not demonstrated for the primary outcome, with a slope difference of 0.10 (95% CI 0.10-0.31) between the two arms. NI was not demonstrated for flare incidence (difference 42.6%, 95% CI 30.0-55.1) or rate of structural damage progression at two years (difference 13.9%, 95% CI -6.7 to 34.4). CONCLUSION: The Towards the Lowest Efficacious Dose trial failed to demonstrate NI for the proposed ABA or TCZ tapering strategy.

Microbiological diagnosis of suspected vertebral osteomyelitis with a focus on the yield of percutaneous needle biopsy: a 10-year cohort study.

This study aims to evaluate in patients hospitalized for vertebral osteomyelitis (VO) the effectiveness of bacteriological diagnosis and the yield of percutaneous needle biopsy (PNB) and to identify factors associated with the result of PNB. This retrospective, two-centre study was conducted between 2000 and 2009. Data on patients with VO were retrieved from the diagnosis database and confirmed by checking medical records. A total of 300 patients with VO were identified; 31 received antibiotics without bacteriological diagnosis, and 269 patients with spondylodiscitis imaging were included. Eighty-three (30.9%) and 18 (6.7%) infections were documented by blood cultures and by bacteriological samples other than PNB, respectively; 168 patients with no bacteriological diagnosis had PNB. Of these, 92 (54.8%) were positive and identified the pathogen and 76 (45.2%) were negative. The most common bacteria were Staphylococcus aureus (34.3%), Streptococcus spp. (20.6%) and coagulase-negative staphylococcus (14.8%). After multivariate analysis, the only factor associated with negative PNB was previous antibiotic intake (OR: 2.31 [1.07-5.00]). When VO was suspected on imaging, bacteriological investigation identified the microorganism in 209/300 (70%) of the cases. The yield of PNB was 54.8%. The only predictor of PNB negativity was previous antibiotic intake. Therefore, we believe that a second PNB should be done after a sufficient delay withdrawal of antibiotics if the first sample was negative. The study was retrospectively registered by the local ethics committee (N°E2019-61).

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.

Analgesic effect of sacroplasty in osteoporotic sacral fractures: a study of six cases.

OBJECTIVES: To evaluate the short-term analgesic effect of sacroplasty in patients with osteoporotic sacral fractures. METHODS: Single-center retrospective observational study of all patients managed with sacroplasty for osteoporotic sacral fractures between October 2008 and November 2009. For each patient, symptom duration, pain intensity, and analgesic consumption were recorded. Sacroplasty was performed under local analgesia, in the prone position, with computed tomography guidance. The long-axis approach was sued to introduce the needles and polymethylmethacrylate cement along the fracture line(s). Pain was evaluated on a 10-point visual analog scale (VAS) 24 hours before sacroplasty then at the time of weight-bearing resumption 24 hours after the procedure. Hospital stay length before and after the procedures were recorded. RESULTS: We identified six patients (five women and one man) with a mean age of 83.2 years. All six patients presented with low back pain and four also had buttock pain. The interval from pain onset to diagnosis ranged from 1 month to 1 year. All patients reported that pain onset followed a fall. The mean VAS pain score was 8.2 before sacroplasty and decreased by 7.6 points 24 hours after the procedure (with four patients having a score of 0). Mean hospital stay length were 12 days before and 4 days after sacroplasty. All patients required opioid analgesics before sacroplasty. At discharge, analgesic requirements were a step II analgesic in one patient, acetaminophen in one patient, and no analgesics in four patients. No adverse events were recorded. DISCUSSION: The findings from our small population are consistent with a recent literature review of 15 case-series studies showing a significant analgesic effect of sacroplasty. The rapid effect of sacroplasty allows prompt ambulation, thus avoiding complications related to immobility. CONCLUSION: Sacroplasty is effective in relieving pain due to sacral insufficiency fractures.