Comparison of Biological Agent Monotherapy and Associations Including Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis: Literature Review and Meta-Analysis of Randomized Trials

Objective: Update the available evidence comparing biologic disease-modifying antirheumatic drugs (bDMARDs) in combination with conventional synthetic disease-modifying antirheumatic drugs (CsDMARDs) to bDMARDs in monotherapy in patients with rheumatoid arthritis. Methods: Research was limited to randomized controlled trials. Major outcome: ACR 20 response criteria at 24 weeks. Secondary outcomes: clinical and radiographic criteria at week 24, 52 and 104. Results: 23 trials (6358 patients), including seven bDMARDs and one other molecule: Anbainuo (anti-TNF-R). No study satisfied our search criteria for anakinra, certolizumab and infliximab. Compared to bDMARD monotherapy, combination therapy gives a better ACR 20 at 24 weeks (RR: 0.88 (0.84–0.94)) in fixed and random effect models, and this result is sustained at 52 and 104 weeks. The results were mostly similar for all other outcomes without increasing the risk of adverse effects. Conclusion: This meta-analysis confirms the superiority of combination therapy over monotherapy in rheumatoid arthritis, in accordance to the usual guidelines

Pattern of improvement in upper limb pointing task kinematics after a 3-month training program with robotic assistance in stroke

Abstract Background When exploring changes in upper limb kinematics and motor impairment associated with motor recovery in subacute post stroke during intensive therapies involving robot-assisted training, it is not known whether trained joints improve before non-trained joints and whether target reaching capacity improves before movement accuracy. Methods Twenty-two subacute stroke patients (mean delay post-stroke at program onset 63 ± 29 days, M2) underwent 50 ± 17 (mean ± SD) 45-min sessions of robot-assisted (InMotion™) shoulder/elbow training over 3 months, in addition to conventional occupational therapy. Monthly evaluations (M2 to M5) included Fugl-Meyer Assessment (FM), with subscores per joint, and four robot-based kinematic measures: mean target distance covered, mean velocity, direction accuracy (inverse of root mean square error from straight line) and movement smoothness (inverse of mean number of zero-crossings in the velocity profile). We assessed delays to reach statistically significant improvement for each outcome measure. Results At M5, all clinical and kinematic parameters had markedly improved: Fugl-Meyer, +65% (median); distance covered, +87%; mean velocity, +101%; accuracy, +134%; and smoothness, +96%. Delays to reach statistical significance were M3 for the shoulder/elbow Fugl-Meyer subscore (+43%), M4 for the hand (+80%) and M5 for the wrist (+133%) subscores. For kinematic parameters, delays to significant improvements were M3 for distance (+68%), velocity (+65%) and smoothness (+50%), and M5 for accuracy (+134%). Conclusions An intensive rehabilitation program combining robot-assisted shoulder/elbow training and conventional occupational therapy was associated with improvement in shoulder and elbow movements first, which suggests focal behavior-related brain plasticity. Findings also suggested that recovery of movement quantity related parameters (range of motion, velocity and smoothness) might precede that of movement quality (accuracy). Trial registration EudraCT 2016–005121-36 . Date of Registration: 2016–12-20. Date of enrolment of the first participant to the trial: 2009–11-24 (retrospective data)

Treatment times, functional outcome, and hemorrhage rates after switching to tenecteplase for stroke thrombolysis: Insights from the TETRIS registry

International audienceIntroduction: The encouraging efficacy and safety data on intravenous thrombolysis with tenecteplase in ischemic stroke and its practical advantages motivated our centers to switch from alteplase to tenecteplase. We report its impact on treatment times and clinical outcomes. Methods: We retrospectively analyzed clinical and procedural data of patients treated with alteplase or tenecteplase in a comprehensive (CSC) and a primary stroke center (PSC), which transitioned respectively in 2019 and 2018. Tenecteplase enabled in-imaging thrombolysis in the CSC. The main outcomes were the imaging-to-thrombolysis and thrombolysis-to-puncture times. We assessed the association of tenecteplase with 3-month functional independence and parenchymal hemorrhage (PH) with multivariable logistic models. Results: We included 795 patients, 387 (48.7%) received alteplase and 408 (51.3%) tenecteplase. Both groups (tenecteplase vs alteplase) were similar in terms of age (75 vs 76 years), baseline NIHSS score (7 vs 7.5) and proportion of patients treated with mechanical thrombectomy (24.1% vs 27.5%). Tenecteplase patients had shorter imaging-to-thrombolysis times (27 vs 36 min, p < 0.0001) mainly driven by patients treated in the CSC (22 vs 38 min, p < 0.001). In the PSC, tenecteplase patients had shorter thrombolysis-to-puncture times (84 vs 95 min, p = 0.02), reflecting faster interhospital transfer for MT. 3-month functional independence rate was higher in the tenecteplase group (62.8% vs 53.4%, p < 0.01). In the multivariable analysis, tenecteplase was significantly associated with functional independence (OR a 1.68, 95% CI 1.15–2.48, p < 0.01), but not with PH (OR a 0.68, 95% CI 0.41–1.12, p = 0.13). Conclusion: Switch from alteplase to tenecteplase reduced process times and may improve functional outcome, with similar safety profile

Functional Outcome, Recanalization, and Hemorrhage Rates After Large Vessel Occlusion Stroke Treated With Tenecteplase Before Thrombectomy

International audienceObjective: To investigate in routine care the efficacy and safety of IV thrombolysis (IVT) with tenecteplase prior to mechanical thrombectomy (MT) in patients with large vessel occlusion acute ischemic strokes (LVO-AIS), either secondarily transferred after IVT or directly admitted to a comprehensive stroke center (CSC).Methods: We retrospectively analyzed clinical and procedural data of patients treated with 0.25 mg/kg tenecteplase within 270 minutes of LVO-AIS who underwent a brain angiography. The main outcome was 3-month functional independence (modified Rankin scale score ≤ 2). Recanalization (revised Treatment in Cerebral Ischemia score 2b-3), was evaluated before (pre-MT) and after MT (final).Results: We included 588 patients (median age 75 years [interquartile range (IQR) 61-84]; 315 women [54%]; median NIH Stroke Scale [NIHSS] score 16 [IQR 10-20]), of which 520 (88%) were secondarily transferred after IVT. Functional independence occurred in 47% (n = 269/570; 95%CI 43.0-51.4) of patients. Pre-MT recanalization occurred in 120 patients (20.4%; 95%CI 17.2-23.9), at a similar rate across treatment paradigms (direct admission, n = 14/68 [20.6%]; secondary transfer, n = 106/520 [20.4%]; p > .99) despite a shorter median IVT-to-puncture time in directly admitted patients (38 [IQR 23-55] vs 86 [IQR 70-110] minutes; p < .001). Final recanalization was achieved in 492 patients (83.7%; 95%CI 80.4-86.6). Symptomatic intracerebral hemorrhage occurred in 2.5% of patients (n = 14/567; 95%CI 1.4-4.1).Conclusions: Tenecteplase before MT is safe, effective and achieves a fast recanalization in everyday practice in patients secondarily transferred or directly admitted to a CSC, in line with published results. These findings should encourage its wider use in bridging therapy.Classification of evidence: This study provides class IV evidence that tenecteplase within 270 minutes of LVO-AIS is increases the probability of functional independence