The effect of tofacitinib on residual pain in patients with rheumatoid arthritis and psoriatic arthritis

Objective: Post hoc analysis of pooled data from 9 randomised controlled trials to assess the effect of tofacitinib (oral Janus kinase inhibitor for treatment of rheumatoid arthritis [RA] and psoriatic arthritis [PsA]) on residual pain in patients with RA or PsA with abrogated inflammation. Methods: Patients who received ≥1 dose of tofacitinib 5 mg twice daily (BID), adalimumab or placebo with/without background conventional synthetic disease-modifying antirheumatic drugs and had abrogated inflammation (swollen joint count [SJC]=0 and C reactive protein [CRP] Results: From the total RA/PsA population, 14.9% (382/2568), 17.1% (118/691) and 5.5% (50/909) of patients receiving tofacitinib, adalimumab and placebo, respectively, had abrogated inflammation after 3 months’ therapy. RA/PsA patients with abrogated inflammation receiving tofacitinib/adalimumab had higher baseline CRP versus placebo; RA patients receiving tofacitinib/adalimumab had lower SJC and longer disease duration versus placebo. Median residual pain (VAS) at Month 3 was 17.0, 19.0 and 33.5 in RA patients treated with tofacitinib, adalimumab or placebo, and 24.0, 21.0 and 27.0 in PsA patients, respectively. Residual pain reductions with tofacitinib/adalimumab versus placebo were less prominent in PsA versus RA patients, with no significant differences between tofacitinib/adalimumab, per BNMA. Conclusion: Patients with RA/PsA with abrogated inflammation receiving tofacitinib/adalimumab had greater residual pain reduction versus placebo at Month 3. Results were similar between tofacitinib/adalimumab.</p

Patient perception of medical care for psoriatic arthritis in North America and Europe: results from a global patient survey

Objective: To compare perceptions of disease control and treatment satisfaction between patients with psoriatic arthritis (PsA) in North America and Europe, and between participating countries within each region. Methods: Data were collected from patients with self-reported PsA diagnoses using an online survey. Results from questions on perceptions of overall health, disease severity, PsA symptoms, PsA impacts, and treatment satisfaction/preferences were reported using descriptive statistics and chi-square tests. Results: 456 patients from North America (Canada, n=155; US, n=301) and 417 patients from Europe (France, n=123; Spain, n=135; UK, n=159) were included in this analysis. Patients in North America were more likely to rate their overall health as excellent/good compared with those in Europe (49% vs. 14%), but also rate their disease as severe (27% vs. 15%). Despite treatment, patients in North America and Europe still experienced musculoskeletal (92% vs. 91%) and skin/nail (62% vs. 58%) symptoms. Similar proportions of patients in North America vs. Europe experienced a social impact (81% vs. 85%); more patients in Europe vs. North America experienced PsA-related work impacts (83% vs. 74%). Satisfaction with PsA medication was more common in North America (89%) vs. Europe (79%), and more common in Spain (91%) vs. the UK (82%) or France (66%). Across all regions and countries, ≥75% of patients agreed symptoms were controlled. However, ≥66% wished they had more medication choices, and ≥84% wanted to change something about their medication. Conclusion: Although perception of overall health and disease severity varied, many patients from both regions still experienced symptoms despite receiving medications for PsA, wished they had greater choice of medications and/or would like to change an aspect of their medications. While these survey findings are subject to selection bias, they do indicate there is scope to improve the treatment of PsA.</p

French real life effectiveness data for Tofacitinib at 1 year in patients with rheumatoid arthritis: interim results of the observational study, DeFacTo

International audienceBackground. Tofacitinib, an oral Janus Kinase inhibitor, is indicated in the treatment of adult patients (pts) with active, moderate to severe rheumatoid arthritis (RA). At the present time we have no data concerning its efficacy in a French RA population in a real-life setting. Objectives. DeFacTo, is an on-going observational study the principal goal of which is to identify factors predictive of Tofacitinib drug survival in RA patients in real life. Methods. These are the results of interim descriptive analyses of effectiveness data after 1 year of follow up. Results Of the 313 pts enrolled in the study, 276 pts were included in the effectiveness analysis (POP1), 219 of whom were patients with a ≥1-year follow-up (POP2) including 122 patients who, as of 15 March 2021, were continuing to take Tofacitinib therapy. At inclusion, POP1 (n=276) was composed of 77.9% females of mean (± SD) age 59.7 ± 11.7 years, having a median disease duration of 9.1 years [Q1;Q3: 4.1; 19.2], TJC 7.5 ± 5.9 and SJC 5.3 ± 5.1; 115 patients presented with erosions, 206 had RF+ and 202 had ACPA+. The median CRP value was 7.4 [: 3.0; 20.0] mg/l, DAS28-4-CRP was 4.6 ±1.1, and the FACIT-Fatigue score was 28.3 ± 11.3. In all, 96.7% of the pts had received prior treatment with ≥1 csDMARDs, 65.2% with b/tsDMARDs (median = 2 [1; 4]). Tofacitinib was prescribed in combination with a csDMARD in 58.3% of cases. The baseline characteristics of the 122 patients still taking tofacitinib at 12 months were comparable to those of POP1. Results showed continued treatment with tofacitinib in 85.3% of pts with mean duration of treatment of 368 ± 197.1 days and reductions from baseline in the parameters of inflammatory markers, pain and the DAS28 activity scores; 20% of 122 pts were in DAS28-CRP remission (Table 1). Safety findings were similar to those reported previously in clinical studies 1 2

Synthesis of Thresholds of Ocean Acidification Impacts on Echinoderms

Assessing the vulnerability of marine invertebrates to ocean acidification (OA) requires an understanding of critical thresholds at which developmental, physiological, and behavioral traits are affected. To identify relevant thresholds for echinoderms, we undertook a three-step data synthesis, focused on California Current Ecosystem (CCE) species. First, literature characterizing echinoderm responses to OA was compiled, creating a dataset comprised of &amp;gt;12,000 datapoints from 41 studies. Analysis of this data set demonstrated responses related to physiology, behavior, growth and development, and increased mortality in the larval and adult stages to low pH exposure. Second, statistical analyses were conducted on selected pathways to identify OA thresholds specific to duration, taxa, and depth-related life stage. Exposure to reduced pH led to impaired responses across a range of physiology, behavior, growth and development, and mortality endpoints for both larval and adult stages. Third, through discussions and synthesis, the expert panel identified a set of eight duration-dependent, life stage, and habitat-dependent pH thresholds and assigned each a confidence score based on quantity and agreement of evidence. The thresholds for these effects ranged within pH from 7.20 to 7.74 and duration from 7 to 30 days, all of which were characterized with either medium or low confidence. These thresholds yielded a risk range from early warning to lethal impacts, providing the foundation for consistent interpretation of OA monitoring data or numerical ocean model simulations to support climate change marine vulnerability assessments and evaluation of ocean management strategies. As a demonstration, two echinoderm thresholds were applied to simulations of a CCE numerical model to visualize the effects of current state of pH conditions on potential habitat.</jats:p

Climate-driven Aerobic Habitat Loss in the California Current System

Climate warming is expected to intensify hypoxia in the California Current System (CCS), threatening its diverse and productive marine ecosystem. We analyzed past regional variability and future changes in the Metabolic Index (Φ), a species-specific measure of the environment’s capacity to meet temperature-dependent organismal oxygen demand. Across the traits of diverse animals, Φ exhibits strong seasonal to interdecadal variations throughout the CCS, implying that resident species already experience large fluctuations in available aerobic habitat. For a key CCS species, northern anchovy, the long-term biogeographic distribution and decadal fluctuations in abundance are both highly coherent with aerobic habitat volume. Ocean warming and oxygen loss by 2100 are projected to decrease Φ below critical levels in 30 to 50% of anchovies’ present range, including complete loss of aerobic habitat—and thus likely extirpation—from the southern CCS. Aerobic habitat loss will vary widely across the traits of CCS taxa, disrupting ecological interactions throughout the region

Climate-driven Aerobic Habitat Loss in the California Current System

Climate warming is expected to intensify hypoxia in the California Current System (CCS), threatening its diverse and productive marine ecosystem. We analyzed past regional variability and future changes in the Metabolic Index (Φ), a species-specific measure of the environment’s capacity to meet temperature-dependent organismal oxygen demand. Across the traits of diverse animals, Φ exhibits strong seasonal to interdecadal variations throughout the CCS, implying that resident species already experience large fluctuations in available aerobic habitat. For a key CCS species, northern anchovy, the long-term biogeographic distribution and decadal fluctuations in abundance are both highly coherent with aerobic habitat volume. Ocean warming and oxygen loss by 2100 are projected to decrease Φ below critical levels in 30 to 50% of anchovies’ present range, including complete loss of aerobic habitat—and thus likely extirpation—from the southern CCS. Aerobic habitat loss will vary widely across the traits of CCS taxa, disrupting ecological interactions throughout the region

Coastal eutrophication drives acidification, oxygen loss, and ecosystem change in a major oceanic upwelling system.

Global change is leading to warming, acidification, and oxygen loss in the ocean. In the Southern California Bight, an eastern boundary upwelling system, these stressors are exacerbated by the localized discharge of anthropogenically enhanced nutrients from a coastal population of 23 million people. Here, we use simulations with a high-resolution, physical-biogeochemical model to quantify the link between terrestrial and atmospheric nutrients, organic matter, and carbon inputs and biogeochemical change in the coastal waters of the Southern California Bight. The model is forced by large-scale climatic drivers and a reconstruction of local inputs via rivers, wastewater outfalls, and atmospheric deposition; it captures the fine scales of ocean circulation along the shelf; and it is validated against a large collection of physical and biogeochemical observations. Local land-based and atmospheric inputs, enhanced by anthropogenic sources, drive a 79% increase in phytoplankton biomass, a 23% increase in primary production, and a nearly 44% increase in subsurface respiration rates along the coast in summer, reshaping the biogeochemistry of the Southern California Bight. Seasonal reductions in subsurface oxygen, pH, and aragonite saturation state, by up to 50 mmol m-3, 0.09, and 0.47, respectively, rival or exceed the global open-ocean oxygen loss and acidification since the preindustrial period. The biological effects of these changes on local fisheries, proliferation of harmful algal blooms, water clarity, and submerged aquatic vegetation have yet to be fully explored

Induced polarization applied to biogeophysics: recent advances and future prospects

This paper provides an update on the fast‐evolving field of the induced polarization method applied to biogeophysics. It emphasizes recent advances in the understanding of the induced polarization signals stemming from biological materials and their activity, points out new developments and applications, and identifies existing knowledge gaps. The focus of this review is on the application of induced polarization to study living organisms: soil microorganisms and plants (both roots and stems). We first discuss observed links between the induced polarization signal and microbial cell structure, activity and biofilm formation. We provide an up‐to‐date conceptual model of the electrical behaviour of the microbial cells and biofilms under the influence of an external electrical field. We also review the latest biogeophysical studies, including work on hydrocarbon biodegradation, contaminant sequestration, soil strengthening and peatland characterization. We then elaborate on the induced polarization signature of the plant‐root zone, relying on a conceptual model for the generation of biogeophysical signals from a plant‐root cell. First laboratory experiments show that single roots and root system are highly polarizable. They also present encouraging results for imaging root systems embedded in a medium, and gaining information on the mass density distribution, the structure or the physiological characteristics of root systems. In addition, we highlight the application of induced polarization to characterize wood and tree structures through tomography of the stem. Finally, we discuss up‐ and down‐scaling between laboratory and field studies, as well as joint interpretation of induced polarization and other environmental data. We emphasize the need for intermediate‐scale studies and the benefits of using induced polarization as a time‐lapse monitoring method. We conclude with the promising integration of induced polarization in interdisciplinary mechanistic models to better understand and quantify subsurface biogeochemical processes