Janus kinase inhibitors and tumour necrosis factor inhibitors show a favourable safety profile and similar persistence in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: real-world data from the BIOBADASER registry.

OBJECTIVES: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. RESULTS: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. CONCLUSIONS: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.

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.

Associated factors to non-medical and medical use of psychoactive medication among Mexican adolescents and adults in a national household survey.

BACKGROUND: Non-medical use of psychoactive medication is a public health problem. Studies in other contexts indicate that individual sociodemographic characteristics are associated with non-medical use, but these associations have not been assessed in the Mexican context. OBJECTIVES: To estimate the prevalence non-medical and medical use of psychoactive medication among Mexican adolescents and adults' medication users and to estimate the associations between sociodemographic characteristics and non-medical use of psychoactive medication, using data from a nationally representative sample. METHODS: Secondary analysis of data collected from the National Survey of Drug, Alcohol, and Tobacco Consumption (ENCODAT) 2016 to 2017. The analytical sample included people aged 12 to 65 years. The sample was stratified into two age categories: adolescents (12-17 years) and adults (18-65 years). Sub-analyses were performed to describe prevalence of use and non-medical use of psychoactive medication at the state-level. Descriptive statistics and multinomial logistic regression models were used to estimate associations between sociodemographic characteristics and medical, non-medical, and non-use of psychoactive medication in adolescents and adults. RESULTS: Among Mexican medication users in 2016, the national prevalence of non-medical use of psychoactive drugs was 19.6%; 22.2% among adolescents and 19.4% among adults. States adjacent to the US-Mexico border reported the highest levels of non-medical use of psychoactive medication. Illicit drug consumption was associated with non-medical use. Sociodemographic characteristics associated with non-medical use varied between adolescents and adults. CONCLUSIONS: There is a high proportion of non-medical use of psychoactive drugs among Mexican medication users, especially among young people. Understanding factors associated with the misuse of psychoactive medications in Mexico can inform policy for prevention and treatment.

Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial.

Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908-8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

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.

Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis.

OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.

Effect of prevalence of alcohol consumption and tobacco use in Mexican municipalities on early childhood development.

One of the most critical time periods in childhood is from birth to five years of age. Children exposed to alcohol and/or tobacco via family members and neighborhood are at risk for childhood developmental delays. This study evaluated the association of early childhood development with the prevalence of alcohol consumption and tobacco use in Mexican municipalities. This is a cross-sectional study. Early childhood development information from 2,345 children aged from 36 to 59 months was obtained from the 2015 Mexican National Survey of Boys, Girls, and Women (ENIM). Data on alcohol consumption and tobacco use come from the 2016 Mexican National Survey on Drugs, Alcohol, and Tobacco Consumption (ENCODAT). Multilevel logistic models were fitted to evaluate the association of the prevalence of alcohol consumption and tobacco use with the inadequacy of early childhood development. Children living in municipalities with high prevalence of alcohol consumption (OR = 13.410; 95%CI: 2.986; 60.240) and tobacco use (OR = 15.080; 95%CI: 2.040; 111.400) were less likely to be developmentally on track regarding early childhood development after adjustment for individual variables related to the child's development and other environmental variables at municipal level. Childhood exposure to alcohol and tobacco in the neighborhood may directly contribute to inadequate early childhood development. These findings suggest that there is an urgent need to develop effective interventions aimed at reducing alcohol consumption and tobacco use in municipalities to ensure adequate early childhood development.

Safety and effectiveness of bDMARDs during pregnancy in patients with rheumatic diseases: Real-world data from the BIOBADASER registry.

INTRODUCTION: Inflammatory rheumatic diseases usually affect women of childbearing age treated with biologic drugs. However, there is a lack of literature on the efficacy and toxicity of biologic disease-modifying drugs during pregnancy. The aim of this study was to determine the presence of pregnant patients treated with bDMARDs in a real-world dataset and to examine the impact of pregnancy and lactation on the evolution of rheumatic disease in a registry of Spanish patients. METHOD: This was a multicentre prospective study with a real-world setting. Information was obtained from BIOBADASER registry. Patients included are women who got pregnant until November 2020 from 19 rheumatology units. We conducted proportions, means, and standard deviations (SD) to describe the study population and the use of treatments. T-test and Chi-square test were applied to assess differences between groups. RESULT: Ninety cases of pregnancy were registered (n=68 full-term pregnancies; n=22 spontaneous miscarriages). Most of the cases discontinued bDMARDs during pregnancy (78.9%) but 13 cases continued treatment during pregnancy, mainly using certolizumab pegol. These cases were obtaining better management of rheumatic disease, although the differences were not statistically significant [DAS28-CRP, 2.9 (SD: 1.6) vs. 2.0 (1.2), p=.255; DAS28-ESR, 2.2 (1.0) vs. 1.7 (.5), p=.266]. No serious adverse events were reported during pregnancy and lactation. CONCLUSION: Being pregnant is still an uncommon condition in patients with rheumatic diseases and using bDMARDs. Our results show that rheumatic disease tended to progress better during pregnancy in patients who continued to take bDMARDs.

Safety and effectiveness of bDMARDs during pregnancy in patients with rheumatic diseases: Real-world data from the BIOBADASER registry / Seguridad y efectividad de los FAME biológicos durante el embarazo en pacientes con enfermedades reumáticas: datos del mundo real procedentes del registro BIOBADASER

Introduction: Inflammatory rheumatic diseases usually affect women of childbearing age treated with biologic drugs. However, there is a lack of literature on the efficacy and toxicity of biologic disease-modifying drugs during pregnancy. The aim of this study was to determine the presence of pregnant patients treated with bDMARDs in a real-world dataset and to examine the impact of pregnancy and lactation on the evolution of rheumatic disease in a registry of Spanish patients.Method: This was a multicentre prospective study with a real-world setting. Information was obtained from BIOBADASER registry. Patients included are women who got pregnant until November 2020 from 19 rheumatology units. We conducted proportions, means, and standard deviations (SD) to describe the study population and the use of treatments. T-test and Chi-square test were applied to assess differences between groups.Result: Ninety cases of pregnancy were registered (n=68 full-term pregnancies; n=22 spontaneous miscarriages). Most of the cases discontinued bDMARDs during pregnancy (78.9%) but 13 cases continued treatment during pregnancy, mainly using certolizumab pegol. These cases were obtaining better management of rheumatic disease, although the differences were not statistically significant [DAS28-CRP, 2.9 (SD: 1.6) vs. 2.0 (1.2), p=.255; DAS28-ESR, 2.2 (1.0) vs. 1.7 (.5), p=.266]. No serious adverse events were reported during pregnancy and lactation.Conclusion: Being pregnant is still an uncommon condition in patients with rheumatic diseases and using bDMARDs. Our results show that rheumatic disease tended to progress better during pregnancy in patients who continued to take bDMARDs.(AU)

Introducción: Las enfermedades reumáticas inflamatorias afectan normalmente a mujeres en edad fértil tratadas con fármacos biológicos. Sin embargo, escasea la literatura sobre la eficacia y la toxicidad de los fármacos modificadores de la enfermedad (FAME) biológicos durante el embarazo. El objetivo de este estudio fue determinar la presencia de pacientes embarazadas tratadas con FAME biológicos en un conjunto de datos del mundo real y examinar el impacto del embarazo y la lactancia en la evolución de la enfermedad reumática en un registro de pacientes españoles.Método: Estudio prospectivo multicéntrico en un entorno del mundo real. La información se obtuvo del registro BIOBADASER. Los pacientes fueron mujeres embarazadas hasta el mes de noviembre del 2020, de 19 unidades de Rreumatología. Obtuvimos proporciones, medias y desviaciones estándar (DE) para describir la población de estudio y el uso de tratamientos. Se realizaron las pruebas t y χ2 para evaluar las diferencias entre grupos.Resultado:Se registraron 90 casos de embarazo (n=68 embarazos a término; n=22 abortos espontáneos). La mayoría de los casos suspendieron el tratamiento con FAME biológicos durante el embarazo (78,9%), pero 13 casos prosiguieron el tratamiento durante el embarazo, utilizando principalmente certolizumab pegol. Dichos casos obtuvieron un mejor manejo de la enfermedad reumática, aunque las diferencias no fueron estadísticamente significativas (DAS28-CRP, 2,9 [DE 1,6] vs. 2 [1,2], p=0,255; DAS28-ESR, 2,2 [1] vs. 1,7 [0,5], p=0,266). No se reportaron episodios adversos graves durante el embarazo y la lactancia.Conclusión: La situación de embarazo sigue siendo infrecuente en las pacientes con enfermedades reumáticas que utilizan FAME biológicos. Nuestros resultados reflejan que la enfermedad reumática tendió a progresar mejor durante el embarazo en las mujeres tratadas con FAME biológicos.(AU)

Safety outcomes in patients with rheumatoid arthritis treated with abatacept: results from a multinational surveillance study across seven European registries.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept. METHODS: Data were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis [Czech Republic]), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Antirheumatic and Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis [France]), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of the study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as the number of events per 1000 p-y of follow-up with 95% confidence intervals. RESULTS: Over 5000 patients with RA treated with abatacept were included. Most patients (78-85%) were female, and the mean age range was 52-58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y. CONCLUSIONS: Despite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.

Factors associated with discontinuation of biologics in patients with inflammatory arthritis in remission: data from the BIOBADASER registry.

BACKGROUND: The objectives of this study were to assess the discontinuation of biologic therapy in patients who achieve remission and identify predictors of discontinuation of biologics in patients with inflammatory arthritis in remission. METHODS: An observational retrospective study from the BIOBADASER registry comprising adult patients diagnosed with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) and receiving 1 or 2 biological disease-modifying drugs (bDMARDs) between October 1999 and April 2021. Patients were followed yearly after initiation of therapy or until discontinuation of treatment. Reasons for discontinuation were collected. Patients who discontinued bDMARDs because of remission as defined by the attending clinician were studied. Predictors of discontinuation were explored using multivariable regression models. RESULTS: The study population comprised 3,366 patients taking 1 or 2 bDMARDs. Biologics were discontinued owing to remission by 80 patients (2.4%): 30 with RA (1.7%), 18 with AS (2.4%), and 32 with PsA (3.9%). The factors associated with a higher probability of discontinuation on remission were shorter disease duration (OR: 0.95; 95% CI: 0.91-0.99), no concomitant use of classic DMARDs (OR: 0.56; 95% CI: 0.34-0.92), and shorter usage of the previous bDMARD (before the decision to discontinue biological therapy) (OR: 1.01; 95% CI: 1.01-1.02); in contrast, smoking status (OR: 2.48; 95% CI: 1.21-5.08) was associated with a lower probability. In patients with RA, positive ACPA was associated with a lower probability of discontinuation (OR: 0.11; 95% CI: 0.02-0.53). CONCLUSIONS: Discontinuation of bDMARDs in patients who achieve remission is uncommon in routine clinical care. Smoking and positive ACPA in RA patients were associated with a lower probability of treatment discontinuation because of clinical remission.

Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study.

OBJECTIVE: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies. PATIENTS AND METHODS: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model. RESULTS: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i. CONCLUSION: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation.

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.

Female Sex, Age, and Unfavorable Response to Tumor Necrosis Factor Inhibitors in Patients With Axial Spondyloarthritis: Results of Statistical and Artificial Intelligence-Based Data Analyses of a National Multicenter Prospective Registry.

OBJECTIVE: Real-world studies are needed to identify factors associated with response to biologic therapies in patients with axial spondyloarthritis (SpA). The objective was to assess sex differences in response to tumor necrosis factor inhibitors (TNFi) and to explore possible risk factors associated with TNFi efficacy. METHODS: A total of 969 patients with axial SpA (315 females, 654 males) enrolled in the BIOBADASER registry (2000-2019) who initiated a TNFi (first, second, or further lines) were studied. Statistical and artificial intelligence (AI)-based data analyses were used to explore the association of sex differences and other factors to TNFi response, using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), to calculate the BASDAI50, with an improvement of at least 50% of the BASDAI score, and using the Ankylosing Spondylitis Disease Activity Score, calculated using the C-reactive protein level (ASDAS-CRP). RESULTS: Females had a lower probability of reaching a BASDAI50 response with a first line TNFi treatment at the second year of follow-up (P = 0.018) and a lesser reduction of the ASDAS-CRP at this time point. The logistic regression model showed lower BASDAI50 responses to TNFi in females (P = 0.05). Other factors, such as older age (P = 0.004), were associated with unfavorable responses. The AI data analyses reinforced the idea that age at the beginning of the treatment was the main factor associated with an unfavorable response. The combination of age with other clinical characteristics (female sex or cardiovascular risk factors and events) potentially contributed to an unfavorable response to TNFi. CONCLUSION: In this national multicenter registry, female sex was associated with less response to a first-line TNFi by the second year of follow-up. A higher age at the start of the TNFi was the main factor associated with an unfavorable response to TNFi.

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.

Effect of prevalence of alcohol consumption and tobacco use in Mexican municipalities on early childhood development / Efecto de la prevalencia del consumo de alcohol y tabaco en municipios mexicanos sobre el desarrollo durante la primera infancia / Efeito da prevalência do consumo de álcool e tabaco em municípios mexicanos sobre o desenvolvimento durante a primeira infância

Abstract: One of the most critical time periods in childhood is from birth to five years of age. Children exposed to alcohol and/or tobacco via family members and neighborhood are at risk for childhood developmental delays. This study evaluated the association of early childhood development with the prevalence of alcohol consumption and tobacco use in Mexican municipalities. This is a cross-sectional study. Early childhood development information from 2,345 children aged from 36 to 59 months was obtained from the 2015 Mexican National Survey of Boys, Girls, and Women (ENIM). Data on alcohol consumption and tobacco use come from the 2016 Mexican National Survey on Drugs, Alcohol, and Tobacco Consumption (ENCODAT). Multilevel logistic models were fitted to evaluate the association of the prevalence of alcohol consumption and tobacco use with the inadequacy of early childhood development. Children living in municipalities with high prevalence of alcohol consumption (OR = 13.410; 95%CI: 2.986; 60.240) and tobacco use (OR = 15.080; 95%CI: 2.040; 111.400) were less likely to be developmentally on track regarding early childhood development after adjustment for individual variables related to the child's development and other environmental variables at municipal level. Childhood exposure to alcohol and tobacco in the neighborhood may directly contribute to inadequate early childhood development. These findings suggest that there is an urgent need to develop effective interventions aimed at reducing alcohol consumption and tobacco use in municipalities to ensure adequate early childhood development.

Resumen: El grupo de edad que se extiende desde el nacimiento hasta los 5 años es uno de los periodos más críticos en la infancia. Niños expuestos al alcohol y/o al tabaco a través de la familia y vecinos corren el riesgo de sufrir un retraso en el desarrollo infantil. Este estudio evaluó la asociación del desarrollo durante la primera infancia con la prevalencia del consumo de alcohol y tabaco en municipios mexicanos. Se trata de un estudio transversal. Las informaciones sobre el desarrollo durante la primera infancia de 2.345 niños de 36 a 59 meses se obtuvieron a través de la Encuesta Nacional de los Niños, Niñas y Mujeres en México (ENIM) de 2015. Los datos sobre el consumo de alcohol y tabaco son de la Encuesta Nacional de Consumo de Drogas, Alcohol y Tabaco en México (ENCODAT) de 2016. Se ajustaron los modelos logísticos multiniveles para evaluar la asociación de la prevalencia de consumo de alcohol y tabaquismo con desarrollo durante la primera infancia inadecuado. Los niños que viven en municipios que tienen una alta prevalencia de consumo de alcohol (OR = 13,410; IC95%: 2,986; 60,240) y tabaquismo (OR = 15,080; IC95%: 2,040; 111,400) se asociaron con la probabilidad más alta de tener un desarrollo durante la primera infancia inadecuado tras el ajuste de las variables individuales relacionadas al desarrollo del niño y a otras variables ambientales en nivel municipal. La exposición infantil al alcohol y al tabaco en la vecindad puede contribuir directamente a un desarrollo durante la primera infancia inadecuado. Estos hallazgos indican una necesidad urgente de desarrollar intervenciones eficaces destinadas a reducir el consumo de alcohol y tabaquismo en los municipios para asegurar un desarrollo durante la primera infancia adecuado.

Resumo: A faixa etária que se estende do nascimento aos 5 anos de idade é um dos períodos mais críticos na infância. Crianças expostas ao álcool e/ou tabaco por meio de familiares e vizinhos estão em risco de atraso no desenvolvimento infantil. Este estudo avaliou a associação do desenvolvimento durante a primeira infância com a prevalência do consumo de álcool e tabaco em municípios mexicanos. Trata-se de um estudo transversal. As informações sobre o desenvolvimento durante a primeira infância de 2.345 crianças de 36 a 59 meses foram obtidas pela Pesquisa Nacional Sobre Crianças e Mulheres no México (ENIM) de 2015. Os dados sobre consumo de álcool e tabaco são da Pesquisa Nacional sobre Consumo de Drogas, Álcool e Tabaco no México (ENCODAT) de 2016. Modelos logísticos multiníveis foram ajustados para avaliar a associação da prevalência de consumo de álcool e tabagismo com desenvolvimento durante a primeira infância inadequado. Crianças que vivem em municípios com alta prevalência de consumo de álcool (OR = 13,410; IC95%: 2,986; 60,240) e tabagismo (OR = 15,080; IC95%: 2,040; 111,400) foram associadas à maior probabilidade de ter um desenvolvimento durante a primeira infância inadequado após ajuste às variáveis individuais relacionadas ao desenvolvimento da criança e a outras variáveis ambientais em nível municipal. A exposição infantil ao álcool e tabaco na vizinhança pode contribuir diretamente para o desenvolvimento durante a primeira infância inadequado. Estas descobertas demonstram uma necessidade urgente de desenvolver intervenções eficazes destinadas a reduzir o consumo de álcool e tabagismo nos municípios para garantir um desenvolvimento durante a primeira infância adequado.

Realidad de la Reumatología en España y sus comunidades autónomas antes de la pandemia / The reality of Rheumatology in Spain and its autonomous communities before the pandemic

Objetivo: Determinar el número de reumatólogos por 100.000 habitantes en activo en centros públicos o privados en el conjunto de España, por comunidades autónomas y su distribución por edad y sexo. Material y método: Estudio transversal utilizando la información contenida en la base de datos de la Sociedad Española de Reumatología, con datos confirmados por los responsables de los servicios clínicos de cada uno de los hospitales (públicos y privados) disponibles en la base de datos. Se analizó edad, sexo y lugar de trabajo de los reumatólogos en activo en febrero de 2020. Se calcularon tasas de reumatólogos por 100.000 habitantes a partir de datos de población del Instituto Nacional de Estadística. Resultados: Se estimó una tasa de especialistas en reumatología por 100.000 habitantes en España de 2,17. El porcentaje de mujeres fue del 59,7%, siendo superior la proporción mujer/hombre en edades más jóvenes. La menor relación de especialistas por 100.000 habitantes se registró en la Comunidad Valenciana (1,6), y la mayor en Cantabria (3,2). Conclusiones: Se encontraron variaciones en la tasa de reumatólogos por 100.000 habitantes entre comunidades autónomas. La distribución por sexo mostró una tendencia a un incremento de mujeres reumatólogas.(AU)

Objectives: To determine the number of rheumatologists per 100,000 inhabitants working in public or private centres in Spain as a whole, and by Autonomous Community and their distribution by age and sex. Material and method: Cross-sectional study based on the information contained in the database of the Spanish Society of Rheumatology. Quality control was performed by contact (e-mail and telephone call) with the heads of the clinical services of each of the hospitals (public and private). The information analysed was the age, sex and place of work of active rheumatologists in February 2020. The rates of rheumatologists per 100,000 inhabitants were calculated from population data from the National Institute of Statistics. Results: The rate of rheumatology specialists per 100,000 inhabitants in Spain was estimated at 2.17. The percentage of women was 59.7%, with a higher female/male ratio at younger ages. The lowest proportion of specialists per 100,000 inhabitants was in the community of Valencia (1.6), and the highest in Cantabria (3.2). Conclusions: Variations were found in the rate of rheumatologists per 100,000 inhabitants among the Autonomous Communities. The distribution by age and sex showed a tendency towards female rheumatologists, especially in the younger age strata.(AU)

The reality of Rheumatology in Spain and its autonomous communities before the pandemic.

OBJECTIVES: To determine the number of rheumatologists per 100,000 inhabitants working in public or private centres in Spain as a whole, and by Autonomous Community and their distribution by age and sex. MATERIAL AND METHOD: Cross-sectional study based on the information contained in the database of the Spanish Society of Rheumatology. Quality control was performed by contact (e-mail and telephone call) with the heads of the clinical services of each of the hospitals (public and private). The information analysed was the age, sex and place of work of active rheumatologists in February 2020. The rates of rheumatologists per 100,000 inhabitants were calculated from population data from the National Institute of Statistics. RESULTS: The rate of rheumatology specialists per 100,000 inhabitants in Spain was estimated at 2.17. The percentage of women was 59.7%, with a higher female/male ratio at younger ages. The lowest proportion of specialists per 100,000 inhabitants was in the community of Valencia (1.6), and the highest in Cantabria (3.2). CONCLUSIONS: Variations were found in the rate of rheumatologists per 100,000 inhabitants among the Autonomous Communities. The distribution by age and sex showed a tendency towards female rheumatologists, especially in the younger age strata.