Adalimumab or Etanercept as first line biologic therapy in Enthesitis related arthritis (ERA) - a drug-survival single centre study spanning 10 years

Objectives: To analyse and compare drug-survival of adalimumab and etanercept (and their biosimilars) in biologic-naïve patients with ERA (Enthesitis-Related Arthritis). // Methods: In this retrospective observational study, conventional statistics and machine-learning were applied to compare drug-survival (adalimumab, etanercept and their biosimilars initiated: 2009–2019) in ERA and identify determinants. The primary outcome was discontinuation of treatment due to primary- or secondary-failure and adverse drug-reactions. // Results: During the observation period, 99 of 188 patients with ERA on first-line TNF inhibitors (etanercept-n=108, adalimumab-n=80) discontinued their treatment (median survival-time 3.9years, 95%CI 2.6-4.9years). Adalimumab was associated with longer drug-survival compared to etanercept especially after an initial positive response, with the median time to treatment discontinuation 4.9years (95% CI 3.9–5.7) for adalimumab, compared to 2years (95%CI 1.4–4.0) for etanercept (HR of treatment-discontinuation-0.49, 95%CI 0.32–-0.75, p=0.001). Adjusted by propensity-score, adalimumab-methotrexate combination was associated with longer drug survival, compared to adalimumab-monotherapy (HR-0.41, 95%CI 0.20–0.85), etanercept-monotherapy (HR-0.28, 95%CI 0.15–0.53), and etanercept-methotrexate combination (HR-0.39, 95%CI 0.21–0.73). The presence of HLA-B27 was associated with longer drug-survival (HR-0.50, 95%CI 0.29–0.87) following an initial positive response. Higher-CRP at baseline was associated with higher rate of primary-failure (HR-1.68, 95%CI 1.08–2.62). Axial-ERA (sacroiliitis±spinal-involvement) was associated with poorer drug-survival for both primary- and secondary-failure (overall HR-2.03, 95%CI 1.22–3.40). Adjusted by propensity-score, shorter drug-survival was observed in patients with baseline-CRP≥12.15 mg/L, but only in the context of axial-ERA, not in peripheral-ERA (no sacroiliitis/spinal-involvement) (HR-2.28, 95%CI 1.13–-3.64). // Conclusion: Following an initial positive primary response, continuing methotrexate with adalimumab was associated with the longest drug-survival compared to adalimumab-monotherapy or etanercept-based regimens. Axial-ERA was associated with a poorer drug-survival. A CRP >12.15 in patients with axial-ERA was associated with a higher rate of primary-failure. Further prospective studies are required to confirm these findings

Débat sur les perspectives économiques

Xavier Timbeau : Le débat est divisé en trois parties : monde, Union européenne et France. Commençons par la situation mondiale. (Premier paragraphe

The structure and characteristic scales of molecular clouds

The structure of molecular clouds holds important clues regarding the physical processes that lead to their formation and subsequent dynamical evolution. While it is well established that turbulence imprints a self-similar structure onto the clouds, other processes, such as gravity and stellar feedback, can break their scale-free nature. The break of self-similarity can manifest itself in the existence of characteristic scales that stand out from the underlying structure generated by turbulent motions. In this work, we investigate the structure of the Cygnus-X North and Polaris Flare molecular clouds, which represent two extremes in terms of their star formation activity. We characterize the structure of the clouds using the delta-variance (Δ-variance) spectrum. In the Polaris Flare, the structure of the cloud is self-similar over more than one order of magnitude in spatial scales. In contrast, the Δ-variance spectrum of Cygnus-X North exhibits an excess and a plateau on physical scales of ≈0.5−1.2 pc. In order to explain the observations for Cygnus-X North, we use synthetic maps where we overlay populations of discrete structures on top of a fractal Brownian motion (fBm) image. The properties of these structures, such as their major axis sizes, aspect ratios, and column density contrasts with the fBm image, are randomly drawn from parameterized distribution functions. We are able to show that, under plausible assumptions, it is possible to reproduce a Δ-variance spectrum that resembles that of the Cygnus-X North region. We also use a “reverse engineering” approach in which we extract the compact structures in the Cygnus-X North cloud and reinject them onto an fBm map. Using this approach, the calculated Δ-variance spectrum deviates from the observations and is an indication that the range of characteristic scales (≈0.5−1.2 pc) observed in Cygnus-X North is not only due to the existence of compact sources, but is a signature of the whole population of structures that exist in the cloud, including more extended and elongated structures