Anterior Interhemispheric Approach for the Surgical Treatment of Azygos Anterior Cerebral Artery Aneurysms: A Case Series.

The azygos artery is an uncommon vascular variant of the anterior cerebral artery (ACA). This anomaly is associated in a high percentage with aneurysms. Management of azygos ACA aneurysms represents a surgical challenge. We present five patients who underwent microsurgical treatment for distal azygos ACA aneurysms with complex morphology. Four patients showed subarachnoid hemorrhage (SAH) and one complained of sentinel headache. Early preoperative digital subtraction angiography (DSA) or computerized tomography angiography (CTA) was performed. All patients were treated by surgical clipping via an anterior interhemispheric approach. During follow-up, all patients had a satisfactory outcome, with postoperative angiograms showing complete resolution of aneurysms.

Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Full kinetic modeling analysis of [18F]fluorocholine Positron Emission Tomography (PET) at initial diagnosis of high-grade glioma.

PURPOSE: The main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. MATERIALS AND METHODS: Twenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. RESULTS: Tumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808-0.861), SUVmean (r = 0.794-0.851) and TBR (r = 0.643-0.784), p < 0.002. HGG was confirmed in 21 patients, of which those with methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter showed higher mean Ki (p = 0.020), K1 (p = 0.025) and TBR (p = 0.001) than the unmethylated ones. CONCLUSION: [18F]F-CHO uptake kinetics in HGG is best explained by a 2-tissue-compartment model. The conventional static [18F]F-CHO-PET measures have been validated against the perfusion-transport constant (K1) and the net influx rate (Ki) derived from kinetic modeling. A relationship between [18F]F-CHO uptake rate and MGMT methylation is suggested but needs further confirmation.

Psychometric properties of the Spanish SABA Reliance Questionnaire (SRQ) among patients with asthma.

Background: Patient beliefs about their asthma and its treatment may contribute to overreliance on short-acting ß2-agonist (SABA) therapy, leading to increased risk for potentially life-threatening exacerbations. The SABA Reliance Questionnaire (SRQ) is a validated tool for evaluating patients beliefs about SABAs that may lead to overreliance and overuse. Objective: Our aim was to evaluate the psychometric properties of the Spanish version of the SRQ. Methods: This was an observational, cross-sectional, single-country questionnaire validation study in adults with asthma. Reliability (ordinal α) and validity (convergent and discriminant) of SRQ were evaluated. Concurrent validity was assessed with the Beliefs about Medication Questionnaire, the Treatment Satisfaction Questionnaire for Medication, and a visual analog scale item to assess patients' perceptions of the importance of their reliever inhaler. Discriminant validity was assessed through differences in mean SRQ sum score between patients with high adherence to inhaled corticosteroids and those with low adherence, as measured by the Medication Adherence Report Scale-9 and the Test of Adherence to Inhalers. Results: The Spanish-SRQ exhibited good psychometric properties among 131 patients with asthma. Internal consistency was confirmed with an ordinal α of 0.85. All 5 items were useful for measuring patients' beliefs about SABAs that may lead them to be overreliant on SABAs. Concurrent validity with the Beliefs about Medication Questionnaire, Treatment Satisfaction Questionnaire for Medication, and a visual analog scale item assessing patients' perceptions of the importance of their reliever inhaler was demonstrated. Conclusion: The Spanish version of the SRQ is a valid tool for evaluating potential overreliance on SABAs in Spanish-speaking patients to enable early intervention and support.

High-Grade Temporal Ganglioglioma in an Older Adult Woman.

Ganglioglioma (GG) is a WHO-grade 1 glioneuronal neoplasm. It is well differentiated with a slow-growing pattern and is composed of a combination of neoplastic ganglion and glial cells. Anaplastic ganglioglioma (AGG) is an extremely rare malignant variant of ganglioglioma, which is not included in the new WHO classification; however, the term is used to talk about gangliogliomas with data of malignancy. AGGs usually occur in children and young adults and are associated with high recurrence and mortality. The authors describe the case of a 62-year-old woman with AGG. She presented with cacosmia, vertigo, nausea, and focal-onset seizures with secondary generalization. Magnetic resonance imaging (MRI) revealed an intra-axial lesion in the left temporal lobe. She underwent microsurgical resection guided by electrocorticography (ECoG), and a diagnosis of AGG based on microscopic morphology and immunohistochemical analysis was obtained. She was discharged a few days after surgery with subtotal resection of the lesion, no additional neurological deficit, and adequate seizure control. AGG is a very rare and poorly studied entity. It is currently a controversial term used to refer to gangliogliomas with signs of malignancy. It occurs mainly in children and young adults with temporal lobe epilepsy. Total resection is the best prognostic factor, given the unknown efficacy of radiotherapy and chemotherapy. In our case, the patient was an adult woman with a subtotal resection followed by concomitant radiotherapy and chemotherapy, obtaining a mean survival similar to that reported in the literature, so it can be thought that there is a benefit obtained with chemotherapy and radiotherapy despite having performed a subtotal resection of the lesion. Further studies are needed to establish clear diagnostic criteria for AGG, and a multicenter database of AGGs is necessary for a better understanding of the pathology and to offer the best treatment and prognosis.

Patient preferences in chronic immune-mediated inflammatory diseases potentially treated with biological drugs: discrete choice analysis using real-world data analysis.

OBJECTIVES: Immune-mediated inflammatory diseases (IMIDs) represent a high burden due to their chronicity, high prevalence, and associated comorbidities. Chronic patients' preferences must be considered in IMIDs treatment and follow-up. The objective of this study was to further understand patient's preferences in private settings. METHODS: A literature review was performed to choose the most relevant criteria for patients. A D-efficient discrete choice experiment was designed to elicit preferences of adult patients with IMIDs and potential biological treatment prescription. Participants were collected from private practices (rheumatology, dermatology, and gastroenterology) from February to May 2022. Patients chose between option pairs, characterized by six health-care attributes, as well as monthly out-of-pocket drug price. Responses were analyzed through a conditional logit model. RESULTS: Eighty-seven patients answered the questionnaire. The most frequent pathologies were Rheumatoid Arthritis (31%) and Psoriatic Arthritis (26%). The most relevant criteria were choosing the preferred physician (OR 2.25 [SD0.26]); reducing time until visit with specialist (OR 1.79 [SD0.20]), access through primary care (OR 1.60 [SD0.08]), and an increase in monthly out-of-pocket price from 100€ to 300€ (OR 0.55 [SD0.06]) and to 600€ (OR 0.08 [SD0.02]). CONCLUSIONS: Chronic IMIDs patients showed a preference toward a faster, personalized service, even with a trade-off in terms of out-of-pocket price.

Obstructive Hydrocephalus Due to Posterior Fossa Tumors in Adults: A Comparative Analysis of 3 Surgical Techniques.

BACKGROUND: The main treatments for hydrocephalus due to posterior fossa tumors are tumor resection with or without an external ventricular drain, ventriculoperitoneal shunt (VPS), and endoscopic third ventriculostomy. Although preoperative cerebrospinal fluid diversion by any of these techniques improves clinical outcomes, evidence comparing the efficacy of these techniques is scarce. Therefore, we aimed to retrospectively evaluate each treatment modality. METHODS: This single-center study analyzed 55 patients. Treatments were classified as successful (hydrocephalus resolution with a single surgical event) or failed and compared with a χ2 test. Kaplan-Meier curves and log-rank tests were employed. A Cox proportional hazard model was used to determine relevant covariates predicting outcomes. RESULTS: Mean patient age was 36.3 years, 43.4% of patients were men, and 50.9% of patients presented with uncompensated intracranial hypertension. Mean tumor volume was 33.4 cm3, and extent of resection was 90.85%. Tumor resection with or without an external ventricular drain was successful in 58.82% of cases, VPS was successful in 100%, and endoscopic third ventriculostomy was successful in 76.19% (P = 0.014). Mean follow-up time was 15.12 months. Log-rank test found statistically significant differences between survival curves of treatments (P = 0.016) favoring the VPS group. Postoperative surgical site hematoma was a significant covariate in the Cox model (hazard ratio = 17; 95% confidence ratio, 2.301-81.872; P = 0.004). CONCLUSIONS: This study favored VPS as the most reliable treatment of hydrocephalus due to posterior fossa tumors in adult patient; however, several factors influence clinical outcomes. We proposed an algorithm based on our findings and other authors' findings to facilitate the decision-making process.

An Inexpensive Unmanned Aerial Vehicle-Based Tool for Mobile Network Output Analysis and Visualization.

Usage of Unmanned Aerial Vehicles (UAVs) for different tasks is widespread, as UAVs are affordable, easy to manoeuvre and versatile enough to execute missions in a reliable manner. However, there are still fields where UAVs play a minimal role regardless of their possibilities. One of these application domains is mobile network testing and measurement. Currently, the procedures used to measure the main parameters of mobile networks in an area (such as power output or its distribution in a three-dimensional space) rely on a team of specialized people performing measurements with an array of tools. This procedure is significantly expensive, time consuming and the resulting outputs leave a higher degree of precision to be desired. An open-source UAV-based Cyber-Physical System is put forward that, by means of the Galileo satellite network, a Mobile Data Acquisition System and a Graphical User Interface, can quickly retrieve reliable data from mobile network signals in a three-dimensional space with high accuracy for its visualization and analysis. The UAV tested flew at 40.43 latitude and -3.65 longitude degrees as coordinates, with an altitude over sea level of around 600-800 m through more than 40 mobile network cells and signal power displayed between -75 and -113 decibels.

Conventional office blood pressure measurements and unattended automated office blood pressure compared with home self-measurement and 24-h ambulatory blood pressure monitoring.

OBJECTIVE: To assess whether automated office blood pressure (BP) (AOBP) measurement is a better method for measuring BP in the office than conventional techniques and an alternative to out-of-office BP measurements: home-self BP (HSBP) or ambulatory BP monitoring (ABPM). METHODS: We conducted a cross-sectional study of 74 patients and compared AOBP with the conventional technique using a mercury sphygmomanometer and with both out-to-office BP measurements: HSBP of 7 days (three measurements in the morning, afternoon, and night) and daytime ABPM. In addition, we compared BP values obtained using HSBP and ABPM to determine their level of agreement. We used ANOVA to compare means, Bland-Altman, and intraclass correlation coefficients (ICC) for concordance. RESULTS: BP values obtained by the two office methods were similar: conventional 147.2/85.0 mmHg and AOBP 146.0/85.5 mmHg ( P > 0.05) with good agreement (ICC 0.85). The mean SBP differences between AOBP and HSBP ( P < 0.001) and between AOBP and ABPM ( P < 0.001) were 8.6/13.0 mmHg with limits of agreement of -21.2 to 38.5 and -18.4 to 44.3 mmHg, respectively. The average SBP values obtained by HSBP were 4.3 mmHg higher than those obtained by ABPM ( P < 0.01). CONCLUSION: Our study showed good agreement and concordance between the two office methods as well between the two out-to-office methods, although there was a significant difference in the mean SBP between the HSBP and ABPM. Moreover, AOBP was not comparable to either HSBP or ABPM; therefore, the estimation of out-to-office BP using AOBP is not supported.

Initial Treatment with Biological Therapy in Rheumatoid Arthritis.

BACKGROUND: We aimed to analyse the effectiveness, efficiency, and safety of initial treatment with biological therapies in rheumatoid arthritis (RA). METHODS: Qualitative study. A group of RA experts was selected. A scoping review in Medline was conducted to analyse the evidence of initial RA treatment with biological therapies. Randomised clinical trials were selected. Two reviewers analysed the articles and compiled the data, whose quality was assessed using the Jadad scale. The experts discussed the review's findings and generated a series of general principles: Results: Seventeen studies were included. Most of the included patients were middle-aged women with early RA (1-7 months) and multiple poor prognostic factors. Initial treatment with TNF-alpha inhibitors combined with methotrexate (MTX) and an IL6R inhibitor (either in mono or combination therapy) is effective (activity, function, radiographic damage, quality of life), safe, and superior to MTX monotherapy in the short and medium term. In the long term, patients who received initial treatment with biologicals presented better results than those whose initial therapy was with MTX. CONCLUSIONS: Initial treatment of RA with biological therapies is effective, efficient, and safe in the short, medium, and long term, particularly for patients with poor prognostic factors.

A Review of Genetic Polymorphisms and Susceptibilities to Complications after Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) and vasospasm are two complications of subarachnoid hemorrhages (SAHs) which entail high risks of morbidity and mortality. However, it is unknown why only some patients who suffer SAHs will experience DCI and vasospasm. The purpose of this review is to describe the main genetic single nucleotide polymorphisms (SNPs) that have demonstrated a relationship with these complications. The SNP of the nitric oxide endothelial synthase (eNOS) has been related to the size and rupture of an aneurysm, as well as to DCI, vasospasm, and poor neurological outcome. The SNPs responsible for the asymmetric dimetilarginine and the high-mobility group box 1 have also been associated with DCI. An association between vasospasm and the SNPs of the eNOS, the haptoglobin, and the endothelin-1 receptor has been found. The SNPs of the angiotensin-converting enzyme have been related to DCI and poor neurological outcome. Studies on the SNPs of the Ryanodine Receptor yielded varying results regarding their association with vasospasm.

Effectiveness and safety of tocilizumab in monotherapy in biologic-naïve and non-naïve patients with rheumatoid arthritis in a real-world setting.

OBJECTIVE: To evaluate the effectiveness and safety of tocilizumab (TCZ) monotherapy in biologic-naïve patients with rheumatoid arthritis (RA) versus patients with previous biologic exposure in a real-world setting. MATERIALS AND METHODS: Non-controlled clinical-trial, 32-week prospective multicenter study including RA patients with moderate-severe disease activity starting TCZ in monotherapy who had a prior inadequate response or were intolerant to methotrexate (MTX). Effectiveness according to EULAR response evaluated at 24-week and safety at 32-weekwere assessed. RESULTS: Of the 93 were enrolled of whom 84 (90%) were eligible for the effectiveness analysis. Biologic-naïve patients (n=46, 54.8%) were younger (51.5 versus 57.9) with shorter disease duration (6.4 versus 13.3) but presented similar comorbidities in comparison with non-naïve patients. DAS28 remission was achieved in a higher percentage in the group of patients with prior biological treatment. 89 adverse events (AE) were recorded in 50 patients, most of them non-serious AE (non-SAE) (86.3%). CONCLUSIONS: In a real world setting, TCZ exhibit similar effectiveness and safety in monotherapy in patients with RA regardless previous exposure to other biologic therapies. This study provides additional and valuable real-world findings on the use of TCZ in patients with RA.

[Translated article] Spanish Asthma Management Guidelines (GEMA) v.5.1. Highlights and Controversies.

In this fifth phase of development, the contents of the Spanish Asthma Management Guidelines (GEMA), which include versions 5.0 and 5.1, have undergone a thorough review. The aim here is to set the main changes in context. These could be summarized as follows: DIAGNOSIS: new FENO cut-off and severity classification based on treatment needed to maintain control; INTERMITTENT ASTHMA: a more restrictive concept and treatment extended to include a glucocorticoid/adrenergic combination as needed; MILD ASTHMA: glucocorticoid/adrenergic therapy as needed as an alternative in case of low therapeutic adherence to conventional fixed-dose steroids; SEVERE ASTHMA: readjustment of phenotypes, incorporation of triple therapy in a single inhaler, and criteria for selection of a biologic in severe uncontrolled asthma; OTHERS: specific scoring in childhood asthma, incorporation of certain organizational aspects (care circuits, asthma units, telemedicine), new sections on COVID-19 and nasal polyposis.

[Translated article] Spanish COPD Guidelines (GesEPOC) 2021 Update. Diagnosis and Treatment of COPD Exacerbation Syndrome.

This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm3. Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment.

Incidence, Mortality, and Trends of Prostate Cancer in Mexico from 2000 to 2019: Results from the Global Burden of Disease Study 2019.

In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th most common cause of death globally in males. In Mexico, PC epidemiology has been studied by a number of metrics and over various periods, although without including the most up-to-date estimates. Herein, we describe and compare the burdens and trends of PC in Mexico and its 32 states from 2000 to 2019. For this study, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rates (ASR per 100,000 people) of the incidence and mortality of PC. In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6-36.0 thousand) incident cases and 9.2 thousand (7.7-12.7 thousand) deaths in males of all ages in 2019. Among the states, Sinaloa had the greatest ASR of incidence, and Guerrero had the highest mortality. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest.

A Social Return on Investment Analysis of Improving the Management of Chronic Obstructive Pulmonary Disease Within the Spanish National Healthcare System.

Purpose: To define a set of proposals that would improve the current management of chronic obstructive pulmonary disease (COPD) within the Spanish National Healthcare System (SNHS) from a comprehensive multidisciplinary perspective and to assess the impact of its implementation from clinical, healthcare, economic, and social perspectives. Patients and Methods: A group of 20 stakeholders related to COPD (healthcare professionals, patients, and informal caregivers, among others) participated in an online Delphi process to agree on a set of 15 proposals that would improve the current management of COPD within the SNHS in four areas: diagnosis, risk stratification, management of exacerbations, and management of stable COPD. A one-year forecast-type social return on investment (SROI) analysis was used to estimate the impact that implementing the set of proposals would have in relation to the investment required. A sensitivity analysis was used to test the strength of the model when varying assumption-based data-points. Results: The hypothetical implementation of the complete set of 15 proposals would require a €668 million investment and would generate a €2079 million social impact concerning savings for the SNHS and quality of life improvements for patients and their informal caregivers, among others. Accordingly, for every euro invested in the set of proposals, a social return of €3.11 would be generated (€2.71 in the worst-case scenario and €3.62 in the best-case scenario) of both tangible (32.56%) and intangible nature (67.44%). Conclusion: Altogether, implementing this set of 15 proposals would generate a positive social impact, threefold the required investment. The results may inform decisions relative to healthcare policy and practice regarding COPD management within the SNHS, further contributing to reduce the large burden of COPD.

Frequency and Associated Factors of Suicidal Ideation in Patients with Chronic Obstructive Pulmonary Disease.

We aimed to examine the prevalence of suicidal ideation in patients with chronic obstructive pulmonary disease (COPD) and the association between demographic and clinical variables and the occurrence of suicidal thoughts. This was a cross-sectional study. Sociodemographic and clinical data were recorded, and questionnaires were used to assess depressive symptoms (Beck Depression Inventory), comorbidities (Charlson Index), cognitive performance (Mini Mental State Examination), and quality of life (EuroQoL-5 dimensions and CAT). Specific questions about suicide-related behavior were included. Multivariate logistic regression analysis identified the significant factors associated with previous suicidal ideation and suicide attempts. The analysis included 1190 subjects. The prevalence of suicidal ideation and suicide attempts were 12.1% and 2.5%, respectively. Severely depressed patients had the highest prevalence of suicide-related behavior. The adjusted logistic model identified factors significantly associated with suicidal ideation: sex (odds ratio (OR) for women vs. men = 2.722 (95% confidence interval (CI) = 1.771-4.183)), depression score (OR = 1.163 (95% IC = 1.127-1.200)), and Charlson Index (OR 1.228 (95% IC 1.082-1.394)). Suicidal ideation is common in COPD patients, especially in women. While addressing suicidal ideation and suicide prevention, clinicians should first consider the management of depressive symptomatology and the improvement of coping strategies.

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy. METHODS: Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients. FINDINGS: Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi. INTERPRETATION: Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems. FUNDING: The Instituto de Salud Carlos III.