Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes

The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 ± 3.0% for global cartilage and -5.5 ± 4.3% for the medial compartment at 12 months, and -5.7 ± 4.4% and -8.3 ± 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression

The challenge of indication extrapolation for infliximab biosimilars

AbstractA biosimilar is intended to be highly similar to a reference biologic such that any differences in quality attributes (i.e., molecular characteristics) do not affect safety or efficacy. Achieving this benchmark for biologics, especially large glycoproteins such as monoclonal antibodies, is challenging given their complex structure and manufacturing. Regulatory guidance on biosimilars issued by the U.S. Food and Drug Administration, Health Canada and European Medicines Agency indicates that, in addition to a demonstration of a high degree of similarity in quality attributes, a reduced number of nonclinical and clinical comparative studies can be sufficient for approval. Following a tiered approach, clinical studies are required to address concerns about possible clinically significant differences that remain after laboratory and nonclinical evaluations. Consequently, a critical question arises: can clinical studies that satisfy concerns regarding safety and efficacy in one condition support “indication extrapolation” to other conditions? This question will be addressed by reviewing the case of a biosimilar to infliximab that was approved recently in South Korea, Europe, and Canada for multiple indications through extrapolation. The principles discussed should also apply to biosimilars of other monoclonal antibodies that are approved to treat multiple distinct conditions

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration

Background JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. Methods In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. Results We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. Conclusion The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.Peer reviewe

Évaluation quantitative de la composition minéralogique de l'amiante chrysotile par thermogravimétrie

L'investigation de l'utilisation de l'analyse thermogravimétrique (ATG-DTG) comme méthode routinière de la détermination de la composition minéralogique de l'amiante chrysotile a été effectuée sur 9 grades d'origines diverses. À partir des résultats de l'analyse chimique et de l'utilisation adéquate des paramètres expérimentaux (masse, taux de chauffe, type de creuset et atmosphère de balayage}, il a été possible d'identifier et de quantifier la brucite Mg(OH)2, la calcite Caco3 et le chrysotile Mg3Si2O5(0H)4. Cependant, les recherches les plus approfondies n'ont pu permettre une caractérisation valable de la magnésite MgC03. Les raisons de ces difficultés ont été mises en évidence par l'analyse des gaz d'évolution (EGA) qui a confirmé la décomposition simultanée de ce carbonate et du chrysotile. Enfin, une banque de données et un logiciel d'analyse thermique (acquisition, traitement graphique et mise en mémoire des courbes expérimentales)ont été créés dans le but d'améliorer la reproductibilité des analyses et de faciliter l’interprétation des observations

Évaluation quantitative de la composition minéralogique de l'amiante chrysotile par thermogravimétrie

L'investigation de l'utilisation de l'analyse thermogravimétrique (ATG-DTG) comme méthode routinière de la détermination de la composition minéralogique de l'amiante chrysotile a été effectuée sur 9 grades d'origines diverses. À partir des résultats de l'analyse chimique et de l'utilisation adéquate des paramètres expérimentaux (masse, taux de chauffe, type de creuset et atmosphère de balayage}, il a été possible d'identifier et de quantifier la brucite Mg(OH)2, la calcite Caco3 et le chrysotile Mg3Si2O5(0H)4. Cependant, les recherches les plus approfondies n'ont pu permettre une caractérisation valable de la magnésite MgC03. Les raisons de ces difficultés ont été mises en évidence par l'analyse des gaz d'évolution (EGA) qui a confirmé la décomposition simultanée de ce carbonate et du chrysotile. Enfin, une banque de données et un logiciel d'analyse thermique (acquisition, traitement graphique et mise en mémoire des courbes expérimentales)ont été créés dans le but d'améliorer la reproductibilité des analyses et de faciliter l’interprétation des observations

Personal non-commercial use only

ABSTRACT. Objective. Infliximab (IFX) is a therapeutic monoclonal antibody targeting tumor necrosis factor-a indicated in the treatment of chronic inflammatory diseases. IFX is administered by intravenous infusion and may be associated with different types of infusion reactions. Methods. RemiTRAC Infusion (NCT00723905) is a Canadian observational registry in which patients receiving IFX are followed prospectively to document premedication use, adverse events, infusion reactions, and the management of infusion reactions. The primary endpoint was to assess factors associated with infusion reactions. Results. There were 1632 patients enrolled and 24,852 infusions recorded. Most patients (63.1%) were treated for rheumatologic conditions such as rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. Of the 1632 patients, 201 (12.3%) reported at least 1 infusion reaction. Three hundred twenty-two infusions were associated with an infusion reaction (1.3%), and most were mild to moderate in severity (95%). The most common infusion reactions were pruritus (19.9%), flushing (9.9%), or dyspnea (6.2%). Multivariate analysis showed that antihistamines premedication, number of previous infusion reactions, and female sex were significantly associated with an increased incidence of infusion reactions (p &lt; 0.0011). The use of any concomitant immunosuppressant or corticosteroids did not influence the incidence of infusion reactions. Antihistamine premedication was associated with an increased incidence of infusion reactions (OR 1.58, p = 0.0007). Conclusion. This registry shows that in community-based infusion clinics, infusion reactions to IFX are uncommon and mild to moderate in nature. Antihistamines, intravenous steroids, and acetaminophen are widely used as preventative premedication, although this study showed an absence of benefit with thei