Drug effectiveness of 2nd and 3rd TNF inhibitors in psoriatic arthritis - relationship with the reason for withdrawal from the previous treatment.

OBJECTIVE: To investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment. METHODS: Prospectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively). RESULTS: We included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67-70%) and 66% (64-68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi. CONCLUSION: Two-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE.

Impact of multimorbidity on the first ts/bDMARD effectiveness and retention rate after two years of follow-up in patients with rheumatoid arthritis from the BIOBADASER registry.

BACKGROUND: Patients with Rheumatoid Arthritis (RA) have a higher prevalence of comorbidities compared to the general population. However, the implications of multimorbidity on therapeutic response and treatment retention remain unexplored. OBJECTIVES: (a) To evaluate the impact of multimorbidity on the effectiveness of the first targeted synthetic or biologic disease-modifying antirheumatic drug (ts/bDMARD), in patients with RA after 2-year follow-up; (b) to investigate the influence of multimorbidity on treatment retention rate. METHODS: Patients with RA from the BIOBADASER registry exposed to a first ts/bDMARDs were included. Patients were categorized based on multimorbidity status at baseline, defined as a Charlson Comorbidity index (CCI) score ≥ 3. A linear regression model, adjusted for sex and age, was employed to compare the absolute DAS28 score over time after ts/bDMARD initiation between the two groups. The Log-Rank test and Kaplan-Meier curve were used to compare the retention rates of the first ts/bDMARD between the groups. RESULTS: A total of 1128 patients initiating ts/bDMARD were included, with 107 (9.3%) exhibiting multimorbidity. The linear regression model showed significantly higher DAS28 (beta coefficient 0.33, 95%CI:0.07-0.58) over a two-year period in patients with multimorbidity, even after adjusting for age and sex. Finally, no differences in the ts/bDMARD retention rate were found between groups (median 6.94-6.96 years in CCI < 3 vs. 5.68-5.62 in CCI ≥ 3; p = 0.610). CONCLUSIONS: Multimorbidity in patients with RA was associated with greater DAS28 scores within the first two years after ts/bDMARD initiation, in comparison with patients without multimorbidity. A slightly shorter retention rate was found in patients with multimorbidity, although the difference was non-significant.

Patient-Reported Outcomes (PROs) and PRO Remission Rates in 12,262 Biologic-Naïve Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitors in Routine Care.

OBJECTIVE: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset. METHODS: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment. RESULTS: For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years. CONCLUSION: In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs.

Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept: Results from the international TOCERRA and PANABA observational collaborative studies.

OBJECTIVE: To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). METHODS: We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. RESULTS: A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48-0.87] for abatacept, and 1.04 [0.76-1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83-1.47] for abatacept, and 1.30 [0.96-1.78] for tocilizumab. CONCLUSION: After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study).

BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery.

Background: There is growing evidence of the significance of gastrointestinal complaints in the impairment of the intestinal mucosal barrier function and inflammation in fibromyalgia (FM) and in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, data on intestinal permeability and gut barrier dysfunction in FM and ME/CFS are still limited with conflicting results. This study aimed to assess circulating biomarkers potentially related to intestinal barrier dysfunction and bacterial translocation and their association with self-reported symptoms in these conditions. Methods: A pilot multicenter, cross-sectional cohort study with consecutive enrolment of 22 patients with FM, 30 with ME/CFS and 26 matched healthy controls. Plasma levels of anti-beta-lactoglobulin antibodies (IgG anti-ß-LGB), zonulin-1 (ZO-1), lipopolysaccharides (LPS), soluble CD14 (sCD14) and interleukin-1-beta (IL-1ß) were assayed using ELISA. Demographic and clinical characteristics of the participants were recorded using validated self-reported outcome measures. The diagnostic accuracy of each biomarker was assessed using the receiver operating characteristic (ROC) curve analysis. Results: FM patients had significantly higher levels of anti-ß-LGB, ZO-1, LPS, and sCD14 than healthy controls (all P < 0.0001). In ME/CFS patients, levels of anti-ß-LGB, ZO-1, LPS, and sCD14 were significantly higher than controls, but lower than in FM (all P < 0.01), while there was no significant difference in IL-1ß level. In the FM and ME/CFS cohorts, both anti-ß-LGB and ZO-1 correlated significantly with LPS and sCD14 (P < 0.001 for both). In the FM group, both anti-ß-LGB and ZO-1 were correlated significantly with physical and mental health components on the SF-36 scale (P < 0.05); whereas IL-1ß negatively correlated with the COMPASS-31 score (P < 0.05). In the ME/CFS cohort, ZO-1 was positively correlated with the COMPASS-31 score (P < 0.05). The ROC curve analysis indicated a strong ability of anti-ß-LGB, ZO-1, LPS and sCD14 to predictively distinguish between FM and ME/CFS from healthy controls (P < 0.0001). Conclusion: Biomarkers of intestinal barrier function and inflammation were associated with autonomic dysfunction assessed by COMPASS-31 scores in FM and ME/CFS respectively. Anti-ß-LGB antibodies, ZO-1, LPS, and sCD14 may be putative predictors of intestinal barrier dysfunction in these cohorts. Further studies are needed to assess whether these findings are causal and can therefore be applied in clinical practice.

Four-years retention rate of golimumab administered after discontinuation of non-TNF inhibitors in patients with inflammatory rheumatic diseases.

BACKGROUND: In patients with rheumatic diseases, the use of biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) after discontinuation of tumor necrosis factor inhibitors (TNFi) is known to be effective. However, data on the use of TNFi after discontinuation of non-TNFi bDMARDs or tsDMARDs (non-TNFi) are scarce. This study assessed the 4-years golimumab retention in patients with rheumatic diseases when used after discontinuation of non-TNFi. METHODS: Adults with rheumatoid arthritis (RA; n = 72), psoriatic arthritis (PsA; n = 30) or axial spondyloarthritis (axSpA; n = 23) who initiated golimumab after discontinuation of non-TNFi from the Spanish registry of biological drugs (BIOBADASER) were analyzed retrospectively. The retention rate (drug survival or persistence) of golimumab up to 4 years was evaluated. RESULTS: The golimumab retention rate was 60.7% (51.4-68.8) at year 1, 45.9% (36.0-55.2) at year 2, 39.9% (29.8-49.7) at year 3 and 33.4% (23.0-44.2) at year 4. Retention rates did not differ significantly whether golimumab was used as second, third, or fourth/subsequent line of therapy (p log-rank = 0.462). Golimumab retention rates were higher in axSpA or PsA patients than in RA patients (p log-rank = 0.002). When golimumab was administered as third or fourth/subsequent line, the 4-years retention rate after discontinuation of non-TNFi was similar to that after discontinuation of TNFi. CONCLUSION: In patients who discontinued non-TNFi, most of whom received golimumab as third/subsequent line of therapy, one-third of patients remained on golimumab at year 4. Retention rates were higher in patients with axSpA and PsA than in those with RA.

Metabolism disturbance by light/dark cycle switching depends on the rat health status: the role of grape seed flavanols.

Changes in light/dark cycles and obesogenic diets are related to the disruption of circadian rhythms and metabolic disorders. Grape seed flavanols have shown beneficial effects on metabolic diseases and, recently, a circadian system modulation has been suggested to mediate their health-enhancing properties. Therefore, the aim of this study was to evaluate the grape seed (poly)phenol extract (GSPE) effects in healthy and obese rats after a light/dark cycle disruption. Forty-eight rats were fed a standard (STD) or cafeteria (CAF) diet for 6 weeks under STD conditions of a light/dark cycle (12 h light per day, L12). Then, animals were switched to a long (18 h light per day, L18) or short (6 h light per day, L6) photoperiod and administered a vehicle (VH) or GSPE (25 mg kg-1) for 1 week. The results showed changes in serum lipids and insulin and metabolomic profiles dependent on the photoperiod and animal health status. GSPE administration improved serum parameters and increased the Nampt gene expression in CAF rats and modified the metabolomic profile in a photoperiod-dependent manner. Metabolic effects of light/dark disturbance depend on the health status of the rats, with diet-induced CAF-induced obese rats being more affected. Grape seed flavanols improve the metabolic status in a photoperiod-dependent manner and their effects on the circadian system suggest that part of their metabolic effects could be mediated by their action on biological rhythms.

Fucosylated N-glycans as early biomarkers of COVID-19 severity.

Background: The pathological mechanisms of SARS-CoV-2 in humans remain unclear and the unpredictability of COVID-19 progression may be attributed to the absence of biomarkers that contribute to the prognosis of this disease. Therefore, the discovery of biomarkers is needed for reliable risk stratification and to identify patients who are more likely to progress to a critical stage. Methods: Aiming to identify new biomarkers we analysed N-glycan traits in plasma from 196 patients with COVID-19. Samples were classified into three groups according to their severity (mild, severe and critical) and obtained at diagnosis (baseline) and at 4 weeks of follow-up (postdiagnosis), to evaluate their behaviour through disease progression. N-glycans were released with PNGase F and labelled with Rapifluor-MS, followed by their analysis by LC-MS/MS. The Simglycan structural identification tool and Glycostore database were employed to predict the structure of glycans. Results: We determined that plasma from SARS-CoV-2-infected patients display different N-glycosylation profiles depending on the disease severity. Specifically, levels of fucosylation and galactosylation decreased with increasing severity and Fuc1Hex5HexNAc5 was identified as the most suitable biomarker to stratify patients at diagnosis and distinguish mild from critical outcomes. Conclusion: In this study we explored the global plasma glycosignature, reflecting the inflammatory state of the organs during the infectious disease. Our findings show the promising potential of glycans as biomarkers of COVID-19 severity.

Efectividad del mousse de sangrecita y nivel de hemoglobina en los niños de 3 años en las instituciones educativas iniciales, Ica-Perú / Effectiveness of sangrecita mousse little blood and hemoglobin level in children from 3 years of age in the initial educational institutions Ica-Peru

El estudio tuvo como Objetivo: Evaluar la efectividad del mousse de sangrecita en los niveles de hemoglobina en los niños de dos instituciones Educativas iniciales. Materiales y métodos: Estudio Experimental con diseño cuasi experimental de corte longitudinal, la población de estudio estuvo conformada por 80 niños los cuales todos participaron (consentimiento de los padres), 52 niños fueron de la IEI de Ica y 28 de la IEI de Comatrana, para la muestra se realizó un muestreo no probabilístico mediante el descarte de anemia utilizando el analizador de hemoglobina (hemoQ), microcubetas, lancetas y demás implementos, de ellos 9 niños tuvieron una hemoglobina <=11gr/dl quienes ingresaron al programa de mousse de sangrecita. Se elaboró una ficha de control. Resultados: Después de 7 semanas de consumir el mousse de sangrecita los 9 niños que ingresaron al programa de las dos IEI, se evidencio un incremento en sus niveles de hemoglobina superior al primer control. Conclusiones: El consumo de mousse de sangrecita es efectiva en el tratamiento de la anemia en niños de la IEI incrementando el nivel de hemoglobina. (AU)

The Objective of the study was to evaluate the effectiveness of blood mousse on hemoglobin levels in children from two initial educational institutions. Materials and Methods: Study experimental Quasi-experimental desing of longitudinal cut, the study population was made up of 80 children who all participated (parental consent), 52 children were from the IEI of Ica and 28 from the IEI of Comatrana, for the sample a non-probability sampling was carried out by discarding anemia using the hemoglobin analyzer (hemoQ), microcuvettes, lancets andother implements, of them 9 children had a hemoglobin < = 11gr / dl who would enter the blood mousse program. A control sheet was drawn up. Results: After 7 weeks of consuming the blood mousse of the 9 children who entered the program of the two IEI, there was evidence of an increase in their hemoglobin levels higher than the first control. Conclusions: The consumption of blood mousse is effective in the treatment of anemia in children with IEI by increasing the level of hemoglobin. (AU)

Gut Microbiota Influences the Photoperiod Effects on Proanthocyanidins Bioavailability in Diet-Induced Obese Rats.

SCOPE: Polyphenols health effects on obesity are mainly attributed to their metabolites generated after their gastrointestinal digestion, in which gut microbiota plays an important role. Moreover, gut microbiota composition and polyphenols bioavailability are influenced by differences in day light length (photoperiod). Thus, this study evaluates if a grape seed proanthocyanidins (GSPEs) extract bioavailability is influenced by different photoperiod exposure via gut microbiota modulation in an obesogenic context. METHODS AND RESULTS: Cafeteria diet-induced obese Fischer 344 rats are housed under different photoperiod conditions (6, 12, or 18 h of light per day) during 9 weeks and administered with GSPE (25 mg kg-1 ) or GSPE and an antibiotic cocktail (ABX) for the last 4 weeks. Serum GSPE-derived metabolites are quantified by HPLC-MS/MS. CONCLUSION: A higher bioavailability is observed under 6 h light/18 h darkness (L6) compared to 18 h light/6 h darkness (L18). Individual metabolites, especially those from the gut microbiota, are affected by photoperiods. ABX treatment alters these photoperiod-mediated changes. Therefore, these results suggest that gut microbiota plays a key role in the photoperiod effects on GSPE bioavailability in obese rats.

Photoperiod Conditions Modulate Serum Oxylipins Levels in Healthy and Obese Rats: Impact of Proanthocyanidins and Gut Microbiota.

Seasonal rhythms are emerging as a key factor influencing gut microbiota and bioactive compounds functionality as well as several physiological processes such as inflammation. In this regard, their impact on the modulation of oxylipins (OXLs), which are important lipid mediators of inflammatory processes, has not been investigated yet. Hence, we aimed to investigate the effects of photoperiods on OXLs metabolites in healthy and obesogenic conditions. Moreover, we evaluated if the impact of proanthocyanidins and gut microbiota on OXLs metabolism is influenced by photoperiod in obesity. To this purpose, Fischer 344 rats were housed under different photoperiod conditions (L6: 6 h light, L12: 12 h light or L18:18 h light) and fed either a standard chow diet (STD) or a cafeteria diet (CAF) for 9 weeks. During the last 4 weeks, obese rats were daily administered with an antibiotic cocktail (ABX), an oral dose of a grape seed proanthocyanidin extract (GSPE), or with their combination. CAF feeding and ABX treatment affected OXLs in a photoperiod dependent-manner. GSPE significantly altered prostaglandin E2 (PGE2) levels, only under L6 and mitigated ABX-mediated effects only under L18. In conclusion, photoperiods affect OXLs levels influenced by gut microbiota. This is the first time that the effects of photoperiod on OXLs metabolites have been demonstrated.

Brain N-Glycosylation and Lipidomic Profile Changes Induced by a High-Fat Diet in Dyslipidemic Hamsters.

The consumption of diets rich in saturated fats is known to be associated with higher mortality. The adoption of healthy habits, for instance adhering to a Mediterranean diet, has proved to exert a preventive effect towards cardiovascular diseases and dyslipidemia. Little is known about how a suboptimal diet can affect brain function, structure, and the mechanisms involved. The aims of this study were to examine how a high-fat diet can alter the brain N-glycan and lipid profile in male Golden Syrian hamsters and to evaluate the potential of a Mediterranean-like diet to reverse this situation. During twelve weeks, hamsters were fed a normal fat diet (CTRL group), a high-fat diet (HFD group), and a high-fat diet followed by a Mediterranean-like diet (MED group). Out of seventy-two identified N-glycans, fourteen were significant (p < 0.05) between HFD and CTRL groups, nine between MED and CTRL groups, and one between MED and HFD groups. Moreover, forty-nine lipids were altered between HFD and CTRL groups, seven between MED and CTRL groups, and five between MED and HFD groups. Our results suggest that brain N-glycan composition in high-fat diet-fed hamsters can produce events comparable to those found in some neurodegenerative diseases, and may promote brain ageing.

Organic vs. Non-Organic Plant-Based Foods-A Comparative Study on Phenolic Content and Antioxidant Capacity.

A plant's stress response involves the production of phytochemicals, including phenolic compounds. Their synthesis can be modulated by organic (ORG) or non-organic (NORG) farming systems in which they are grown. To examine this issue, thirteen plant-based foods cultivated in ORG and NORG systems were compared in terms of antioxidant capacity, total content of phenolics, anthocyanins, flavan-3-ols and flavonols. The results showed that NORG fruits tended to have higher phenolic compounds content, whereas ORG fruits had more antioxidant capacity. NORG legume stood out for having higher values from all the parameters analyzed in comparison to its ORG equivalent. ORG nuts showed more flavan-3-ols and flavonols than their NORG counterparts, nonetheless, tended to be less antioxidant. ORG vegetables displayed higher phenolics and anthocyanins, which reflected in higher antioxidant capacity than NORG ones. These findings suggest that farming systems differentially modulate phenolic compound composition and antioxidant capacity based on the plant species studied.

After JAK inhibitor failure: to cycle or to switch, that is the question - data from the JAK-pot collaboration of registries.

OBJECTIVES: The expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi. METHODS: This is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders. RESULTS: 365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies. CONCLUSIONS: After failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.

Long-term retention of golimumab treatment in clinical practice in a large cohort of patients with rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis.

AIM: To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors. METHODS: Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) database, assessing all adults who had ever started golimumab >6 months before the analysis for an approved indication (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA]). RESULTS: Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0-73.9) at year 1% and 37.7% (95% CI: 33.3-42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p < 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first-line therapy (hazard ratio [HR] for discontinuation 1.52 for second- and 1.79 for third/later-line vs. first-line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation. CONCLUSION: Based on this retrospective analysis of the BIOBADASER registry, nearly two-fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic.

Fatty acid metabolism in liver and muscle is strongly modulated by photoperiod in Fischer 344 rats.

Circadian and seasonal variations produce variations in physiological processes throughout the day and the year, respectively. In this sense, both the light and the moment of feeding are strong modulators of the central and peripheral clocks. However, little is known about its influence on certain metabolic parameters and on the composition of liver and muscle fatty acids (FA). In the present study, 24 Fischer 344 rats were exposed for 11 weeks to different photoperiods, L6, L12 and L18, with 6, 12 and 18 h of light/day, respectively. They were fed a standard diet. Serum metabolic parameters, gene expression of liver enzymes and gastrocnemius muscle involved in the synthesis, elongation, desaturation and ß-oxidation of FA were analyzed. We have found that exposure to different hours of light has a clear effect on FA composition and gene expression in the liver. Mainly, the biosynthesis of unsaturated FA was altered in the L18 animals with respect to those exposed to L12, while the L6 did not show significant changes. At the muscle level, differences were observed in the concentration of mono and polyunsaturated FA. A multivariate analysis confirmed the differences between L12 and L18 in a significant way. We conclude that exposure to long days produces changes in the composition of liver and muscle FA, as well as changes in the gene expression of oxidative enzymes compared to exposure to L12, which could be a consequence of different seasonal eating patterns.

One-Third of European Patients With Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment.

OBJECTIVE: To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA). METHODS: Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment. RESULTS: Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi. CONCLUSION: Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

Facile and Scalable Synthesis of Metal- and Nitrogen-Doped Carbon Nanotubes for Efficient Electrochemical CO2 Reduction.

Metal- and nitrogen-doped carbon (M-N-C) is a promising material to catalyze electrochemical CO2 reduction reaction (CO2RR). However, most M-N-C catalysts in the literature require complicated synthesis procedures and produce small quantities per batch, limiting the commercialization potential. In this work, we developed a simple and scalable synthesis method to convert metal-impurity-containing commercial carbon nanotubes (CNTs) and nitrogen-containing organic precursors into M-N-C via one-step moderate-temperature (650 °C) pyrolysis without any other treatment nor the need to add metal precursors. Batches of catalysts in varied mass up to 10 g (150 mL in volume) per batch were synthesized, and repeatable catalytic performances were demonstrated. To the best of our knowledge, the 10 g batch is one of the largest batches of CO2RR catalysts synthesized in the literature while requiring minimal synthesis steps. The catalyst possessed single-atomic iron-nitrogen (Fe-N) sites, enabling a high performance of >95% CO product selectivity at a high current density of 400 mA/cm2 and high stability for 45 h at 100 mA/cm2 in a flow cell testing. The catalyst outperformed a benchmark noble-metal nanoparticle catalyst and achieved longer stability than many other reported M-N-C catalysts in the literature. The scalable and cost-effective synthesis developed in this work paves a pathway toward practical CO2RR applications. The direct utilization of metal impurities from raw CNTs for efficient catalyst synthesis with minimal treatment is a green and sustainable engineering approach.

New Polyaniline Derivative with Two Central Ester Groups: Synthesis, Characterization, and Theoretical Study.

A new polyaniline derivative was prepared to study the formation of quinoid-diimine units in its polymer. The monomer and polymer were experimentally and theoretically characterized. Both polymers have one or two electron-withdrawing groups as side substituents. The polymers' quinoid-diimine unit composition is affected by the electron-withdrawing side groups of aniline. The presence of the quinoid-diimine group diminished for the two electron-withdrawing groups of aniline. The polymer conductivity is different than with respect to polyemeraldine, associated with the quinoid-diimine units' composition. The quinoid-diimine composition is strongly increased in the polymer containing one electron-withdrawing group. Moreover, the polymer presented good solubility in organic solvents and moderate thermal stability.