Filgotinib Demonstrates Efficacy in Rheumatoid Arthritis Independent of Smoking Status: Post Hoc Analysis of Phase 3 Trials and Claims-Based Analysis

Objectives: To assess cigarette smoking’s effects on efficacy of the preferential Janus kinase (JAK) 1 inhibitor filgotinib and drug persistence in patients with rheumatoid arthritis (RA). Methods: Efficacy in non-smokers, former smokers, and current smokers from phase 3 filgotinib trials was analyzed, including patients with inadequate response (IR) to methotrexate (MTX) or biologic disease-modifying antirheumatic drugs (bDMARDs) or who were MTX-naïve. Proportions achieving Disease Activity Score in 28 joints with C-reactive protein (DAS28[CRP]) ≤ 3.2 were compared using logistic regression. Retrospective claims-based switching data were reviewed. Results: Week 12 (W12) DAS28(CRP) ≤ 3.2 was achieved by 50, 61, and 62% of MTX-IR non-smokers, former smokers, and current smokers taking filgotinib 200 mg (FIL200) + MTX vs. 23, 16, and 32% taking placebo + MTX (p < 0.001, < 0.001, and 0.001) and 50, 34, and 33% taking adalimumab + MTX (p = 0.97, 0.013, and 0.006 vs. FIL200 + MTX). W12 DAS28(CRP) ≤ 3.2 was achieved by 46, 48, and 32% of bDMARD-IR non-smokers, former smokers, and current smokers taking FIL200 + conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) vs. 16, 23, and 5% taking placebo + csDMARD (p < 0.001, 0.077, and 0.051); 57, 58, and 59% of respective MTX-naïve smoking groups achieved W12 DAS28(CRP) ≤ 3.2 with FIL200 + MTX vs. 28, 37, and 18% with MTX (p < 0.001, 0.026, and < 0.001). Claims data showed former/current smokers were likelier than non-smokers to switch from adalimumab to other biologics or JAK inhibitors. Conclusions: Greater proportions of MTX-IR current/former smokers responded to FIL200 + MTX vs. adalimumab + MTX. In non-smoking MTX-IR, bDMARD-IR, and MTX-naïve patients with RA, FIL200 + MTX demonstrated increased response vs. controls. Current/former smokers were likelier to discontinue adalimumab vs. non-smokers in real-world clinical settings. Trial Registration: NCT02889796, NCT02873936, NCT02886728

Association between acute respiratory disease events and the MUC5B promoter polymorphism in smokers

A single-nucleotide polymorphism (rs35705950) in the mucin 5B (MUC5B) gene promoter is associated with pulmonary fibrosis and interstitial features on chest CT but may also have beneficial effects. In non-Hispanic whites in the COPDGene cohort with interstitial features (n=454), the MUC5B promoter polymorphism was associated with a 61% lower odds of a prospectively reported acute respiratory disease event (P=0.001), a longer time-to-first event (HR=0.57; P=0.006) and 40% fewer events (P=0.016). The MUC5B promoter polymorphism may have a beneficial effect on the risk of acute respiratory disease events in smokers with interstitial CT features

Designing protected area networks that translate international conservation commitments into national action

Most countries have committed to protect 17% of their terrestrial area by 2020 through Aichi Target 11 of the Convention on Biological Diversity, with a focus on protecting areas of particular importance for biodiversity. This means national-scale spatial conservation prioritisations are needed to help meet this target and guide broader conservation and land-use policy development. However, to ensure these assessments are adopted by policy makers, they must also consider national priorities. This situation is exemplified by Guyana, a corner of Amazonia that couples high biodiversity with low economic development. In recent years activities that threaten biodiversity conservation have increased, and consequently, protected areas are evermore critical to achieving the Aichi targets. Here we undertake a cost-effective approach to protected area planning in Guyana that accounts for in-country conditions. To do this we conducted a stakeholder-led spatial conservation prioritisation based on meeting targets for 17 vegetation types and 329 vertebrate species, while minimising opportunity costs for forestry, mining, agriculture and urbanisation. Our analysis identifies 3 millio

TESS hunt for young and maturing exoplanets (THYME). IV. Three small planets orbiting a 120 Myr old star in the pisces-eridanus stream

Young exoplanets can offer insight into the evolution of planetary atmospheres, compositions, and architectures. We present the discovery of the young planetary system TOI 451 (TIC 257605131, Gaia DR2 4844691297067063424). TOI 451 is a member of the 120 Myr old Pisces-Eridanus stream (Psc-Eri). We confirm membership in the stream with its kinematics, its lithium abundance, and the rotation and UV excesses of both TOI 451 and its wide-binary companion, TOI 451 B (itself likely anM-dwarf binary).We identified three candidate planets transiting in the Transiting Exoplanet Survey Satellite data and followed up the signals with photometry from Spitzer and ground-based telescopes. The system comprises three validated planets at periods of 1.9, 9.2, and 16 days, with radii of 1.9, 3.1, and 4.1 R⊗, respectively. The host star is near-solar mass with V=11.0 and H = 9.3 and displays an infrared excess indicative of a debris disk. The planets offer excellent prospects for transmission spectroscopy with the Hubble Space Telescope and the James Webb Space Telescope, providing the opportunity to study planetary atmospheres that may still be in the process of evolving

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research