The socioeconomic status of patients with ankylosing spondylitis and its association with the burden of the disease and permanent disability: a cross-sectional cluster analysis.

Background: Few studies have been conducted to investigate the socioeconomic profiles of patients with ankylosing spondylitis (AS) and their associations with disease severity and disability. Objectives: The objectives of this study were to identify clusters of patients with AS according to their socioeconomic characteristics and to evaluate the associations between these clusters and the severity of the disease and permanent disability. Design: This was a cross-sectional and multicentre study. Methods: Patients with AS from the REGISPONSER study were included in this analysis. A cluster analysis was conducted using information on sociodemographic (age, sex, race, marital status, education) and socioeconomic (employment, profession, housing conditions and social level) characteristics. Disease burden and permanent disability were compared between the different clusters using logistic regression adjusted for disease duration and disease activity. Results: A total of 866 patients with AS were included. Two clusters were identified according to socioeconomic characteristics: Cluster 1 (n = 476), with a predominantly low socioeconomic profile, and Cluster 2 (n = 390), with a predominantly high socioeconomic profile. After adjusting for disease duration, patients in Cluster 1 had a longer diagnosis delay, greater body mass index and greater structural damage than those in Cluster 2. Access to biologic disease-modifying anti-rheumatic drugs (bDMARDs) was similar for both groups. However, patients in Cluster 1 had a greater prevalence of permanent disability than those in Cluster 2 after adjusting for disease duration and disease activity (30.8% vs 13.2%, odds ratio 2.58 (95% confidence interval 1.76-3.83)). Conclusion: This study suggests that the socioeconomic status of patients with AS may have implications for disease severity and permanent disability, despite the similar use of bDMARDs.

PRECISE: Preoperative Radiation Therapy to Elicit Critical Immune Stimulating Effects - A Phase 2 Clinical Trial.

PURPOSE: Radiation therapy is an underinvestigated tool for priming the immune system in intact human breast cancers. We sought here to investigate if a preoperative radiation therapy boost delivered was associated with a significant change in tumor-infiltrating lymphocytes (TILs) in the tumor in estrogen receptor positive, HER2Neu nonamplified breast cancers. METHODS AND MATERIALS: A total of 20 patients were enrolled in a phase 2 clinical trial and received either 7.5 Gy × 1 fraction or 2 Gy × 5 fractions, completed 6 to 8 days before surgery. Percent stromal TILs were evaluated on hematoxylin and eosin-stained samples. Short-term safety was assessed based on time to surgery, toxicities, and cosmesis up to 6 months after boost. RESULTS: Stromal TIL increased 6 to 8 days after completion of boost radiation therapy (median 3.0 [IQR, 1.0-6.5]) before radiation therapy versus median 5.0 (IQR, 1.5-8.0) after radiation therapy, P = .0037. Zero grade ≥3 toxicities up to 6 months after boost were experienced. In all, 94% (16/17) patients with 6-month follow-up cosmetic assessment after breast conservation had good-excellent cosmesis by physician assessment. CONCLUSION: In this phase 2 trial, preoperative radiation therapy boost resulted in a short-term increase in stromal TIL with minimal toxicities. Preoperative breast radiation therapy appears to be safe and may be a feasible means for priming the tumor microenvironment.

Clinical and molecular insights into cardiovascular disease in psoriatic patients and the potential protective role of apremilast.

Psoriatic disease, encompassing both psoriasis (Pso) and psoriatic arthritis (PsA), is closely intertwined with a significantly elevated risk of developing cardiovascular diseases. This connection is further compounded by a higher prevalence of cardiometabolic comorbidities, including type 2 diabetes, obesity, insulin resistance, arterial hypertension, and dysregulated lipid profiles. These comorbidities exceed the rates seen in the general population and compound the potential for increased mortality among those living with this condition. Recognizing the heightened cardiometabolic risk inherent in psoriatic disease necessitates a fundamental shift in the treatment paradigm. It is no longer sufficient to focus solely on mitigating inflammation. Instead, there is an urgent need to address and effectively manage the metabolic parameters that have a substantial impact on cardiovascular health. Within this context, apremilast emerges as a pivotal treatment option for psoriatic disease. What sets apremilast apart is its dual-action potential, addressing not only inflammation but also the critical metabolic parameters. This comprehensive treatment approach opens up new opportunities to improve the well-being of people living with psoriatic disease. This review delves into the multifaceted aspects involved in the development of cardiovascular disease and its intricate association with psoriatic disease. We then provide an in-depth exploration of the pleiotropic effects of apremilast, highlighting its potential to simultaneously mitigate metabolic complications and inflammation in individuals affected by these conditions.

Different Therapeutic Response to Anti-TNF Drugs in Patients with Axial Spondyloarthritis Depending on Their Clinical Profile: An Unsupervised Cluster Analysis.

Background: The objectives were as follows: (a) to identify, among patients with axial spondyloarthritis (axSpA), "clusters" of patients based on the presence of peripheral and extra-musculoskeletal manifestations (EMMs) and (b) to compare the effectiveness of the first anti-TNF drugs across the different clusters after 6 months of follow-up. Methods: An observational and retrospective study of 90 axSpA patients naïve to bDMARDs was conducted. An unsupervised cluster analysis using the "k-means" technique was performed using variables of peripheral and EMMs. Baseline clinical and sociodemographic characteristics were evaluated, and the response to anti-TNF treatment (considering responders as those with an improvement ≥1.1 for the Ankylosing Spondylitis Disease Activity Score (ASDAS) or ≥2.0 for the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) was compared across the clusters after 6 months of follow-up. Results: Two clusters were identified: cluster 1 (n = 14), with a higher prevalence of peripheral manifestations, inflammatory bowel disease (IBD), and HLA-B27-positive status, and a lower prevalence of uveitis in comparison with cluster 2 (n = 76). Patients from cluster 1 experienced a more pronounced absolute improvement in ASDAS and BASDAI indices after 6 months. The percentage of responders after 6 months of follow-up was superior in cluster 1 compared to cluster 2 (85.7% vs. 48.7%, p = 0.011). Conclusion: This study suggests the existence of two clinical profiles in axSpA patients according to the peripheral and EMMs, with higher rates of anti-TNF effectiveness after 6 months in those with a greater presence of peripheral features.

Bone metabolism and inflammatory biomarkers in radiographic and non-radiographic axial spondyloarthritis patients: a comprehensive evaluation.

Introduction: Axial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients. Methods: A cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay. Results: R-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others. Conclusion: Altogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation.

Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs.

BACKGROUND & OBJECTIVES: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. PATIENTS & METHODS: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). RESULTS: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. CONCLUSIONS: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.

New advances in genomics and epigenetics in antiphospholipid syndrome.

APS patients exhibit a wide clinical heterogeneity in terms of the disease's origin and progression. This diversity can be attributed to consistent aPL profiles and other genetic and acquired risk factors. Therefore, understanding the pathophysiology of APS requires the identification of specific molecular signatures that can explain the pro-atherosclerotic, pro-thrombotic and inflammatory states observed in this autoimmune disorder. In recent years, significant progress has been made in uncovering gene profiles and understanding the intricate epigenetic mechanisms and microRNA changes that regulate their expression. These advancements have highlighted the crucial role played by these regulators in influencing various clinical aspects of APS. This review delves into the recent advancements in genomic and epigenetic approaches used to uncover the mechanisms contributing to vascular and obstetric involvement in APS. Furthermore, we discuss the implementation of novel bioinformatics tools that facilitate the investigation of these mechanisms and pave the way for personalized medicine in APS.

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.

Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling.

Introduction: RA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways. Methods: This study included two cohorts of RA patients: newly diagnosed individuals (n=25) and those with established RA (disease duration >25 years, n=25). Both cohorts were age and sex-matched with a control group (n=25). Additionally, a longitudinal investigation was conducted on a cohort of 25 RA patients treated with methotrexate and another cohort of 25 RA patients treated with tofacitinib for 6 months. Clinical and analytical variables were recorded, and serum profiling of 184 proteins was performed using the Olink technology platform. Results: RA patients exhibited elevated levels of 75 proteins that might be associated with cardiovascular disease. In addition, 24 proteins were increased in RA patients with established disease. Twenty proteins were commonly altered in both cohorts of RA patients. Among these, elevated levels of CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1 and CCL18 discriminated RA patients and HDs with high specificity and sensitivity. Methotrexate treatment significantly reduced the levels of 13 proteins, while tofacitinib therapy modulated the expression of 10 proteins. These reductions were associated with a decrease in DAS28. Baseline levels of SAA4 and high levels of BNP were associated to the non-response to methotrexate. Changes in IL6 levels were specifically linked to the response to methotrexate. Regarding tofacitinib, differences in baseline levels of LOX1 and CNDP1 were noted between non-responder and responder RA patients. In addition, response to tofacitinib correlated with changes in SAA4 and TIMD4 levels. Conclusion: In summary, this study pinpoints molecular changes linked to cardiovascular disease in RA and proposes candidate protein biomarkers for distinguishing RA patients from healthy individuals. It also highlights how methotrexate and tofacitinib impact these proteins, with distinct alterations corresponding to each drug's response, identifying potential candidates, as SAA4, for the response to these therapies.

Assessment of The Utility of The Sarcoma DNA Methylation Classifier In Surgical Pathology.

Diagnostic classification of soft tissue tumors is based on histology, immunohistochemistry, genetic findings, and radiologic and clinical correlations. Recently, a sarcoma DNA methylation classifier was developed, covering 62 soft tissue and bone tumor entities. The classifier is based on large-scale analysis of methylation sites across the genome. It includes DNA copy number analysis and determines O 6 methylguanine DNA methyl-transferase methylation status. In this study, we evaluated 619 well-studied soft tissue and bone tumors with the sarcoma classifier. Problem cases and typical examples of different entities were included. The classifier had high sensitivity and specificity for fusion sarcomas: Ewing, synovial, CIC -rearranged, and BCOR -rearranged. It also performed well for leiomyosarcoma, malignant peripheral nerve sheath tumors (MPNST), and malignant vascular tumors. There was low sensitivity for diagnoses of desmoid fibromatosis, neurofibroma, and schwannoma. Low specificity of matches was observed for angiomatoid fibrous histiocytoma, inflammatory myofibroblastic tumor, Langerhans histiocytosis, schwannoma, undifferentiated sarcoma, and well-differentiated/dedifferentiated liposarcoma. Diagnosis of lipomatous tumors was greatly assisted by the detection of MDM2 amplification and RB1 loss in the copy plot. The classifier helped to establish diagnoses for KIT-negative gastrointestinal stromal tumors, MPNSTs with unusual immunophenotypes, and undifferentiated melanomas. O 6 methylguanine DNA methyl-transferase methylation was infrequent and most common in melanomas (35%), MPNSTs (11%), and undifferentiated sarcomas (11%). The Sarcoma Methylation Classifier will likely evolve with the addition of new entities and refinement of the present methylation classes. The classifier may also help to define new entities and give new insight into the interrelationships of sarcomas.

Reemplazo percutáneo de válvulas cardíacas derechas con técnica "válvula en válvula" en cardiopatías congénitas: experiencia inicial en Argentina

INTRODUCCIÓN: El reemplazo quirúrgico con colocación de bioprótesis es una estrategia utilizada frecuentemente para tratar valvulopatías en cardiopatías congénitas. OBJETIVO: Presentar la experiencia inicial en Argentina con fractura/remodelación del anillo valvular en bioprótesis y posterior reemplazo percutáneo "válvula en válvula" en pacientes con cardiopatías congénitas. MATERIAL y métodos: Estudio descriptivo y observacional. Se incluyeron todos los pacientes tratados con reemplazo percutáneo debido a disfunción de prótesis valvular biológica. RESULTADOS: Desde agosto de 2021 hasta mayo de 2023, 5 pacientes (3 de sexo femenino) con disfunción de bioprótesis derechas recibieron tratamiento percutáneo como alternativa a la realización de un nuevo reemplazo quirúrgico. La edad media fue 21,2 ± 9,2 años, el peso medio fue 56,2 ± 22,2 kg. Fueron implantadas cinco válvulas balón expandibles: 3 en posición pulmonar y 2 en posición tricúspide y en 4 casos, con fractura previa del anillo valvular. En todos los pacientes se restauró la función valvular, sin complicaciones. En el seguimiento, en un sólo paciente se objetivó insuficiencia valvular moderada derecha CONCLUSIÓN: El reemplazo percutáneo "válvula en válvula" en bioprótesis disfuncionantes derechas es una estrategia atractiva y segura en casos seleccionados, que restaura la competencia y elimina las obstrucciones. Esta estrategia es una opción razonable como alternativa a la realización de un nuevo recambio valvular quirúrgico.

Identification of the first signs or symptoms in different spondyloarthritis subtypes and their association with HLA-B27: data from REGISPONSER and RESPONDIA registries.

OBJECTIVE: To describe and analyse the initial symptoms attributable to patients with spondyloarthritis (SpA) and their association with HLA-B27 status. METHODS: This was an observational, cross-sectional and multicentre study with patients who fulfilled the European Spondyloarthropathy Study Group criteria for SpA from the Registry of Spondyloarthritis of Spanish Rheumatology (REGISPONSER) and Ibero-American Registry of Spondyloarthropathies (RESPONDIA) united registries. Differences in the first sign(s) or symptom(s) were compared across diagnoses and between HLA-B27 status. The diagnostic delay between patients who start the disease with musculoskeletal manifestations (MMs) and extra-MMs (EMMs) was compared. RESULTS: A total of 4067 patients were included (2208 from REGISPONSER and 1859 from RESPONDIA) (ankylosing spondylitis (AS): 68.3%, psoriatic arthritis (PsA): 19.9%, undifferentiated SpA: 11.8%). Overall, 3624 (89.1%) patients initiated the disease with MMs and 443 (10.9%) with EMMs. Low back pain (61.7%) and lower-limb arthritis (38.5%) were the most frequent initial symptoms. In AS patients, the absence of HLA-B27 seems to be related to an increase in the probability of starting the disease with cervical pain and peripheral manifestations. In PsA, the onset of arthritis and psoriasis was more prevalent in HLA-B27-negative patients, while initiation with axial manifestations was more predominant in HLA-B27-positive patients. The diagnostic delay was longer in patients with initial MMs than in those with EMMs (7.2 (34.8) vs 4.5 (7.6) years, respectively). CONCLUSION: In this SpA population, MMs were the most prevalent initial symptoms, with differences across diagnoses and depending on the presence of the HLA-B27 antigen.

Enthesitis indices identify different patients with this characteristic in axial and peripheral spondyloarthritis and also in psoriatic arthritis: ASAS-PerSpA data.

BACKGROUND: In axial spondyloarthritis (axSpA), peripheral SpA (pSpA) and psoriatic arthritis (PsA), enthesitis is a hallmark clinical feature that can be assessed by the SPARCC index, LEI, MASES and MEI. These indices evaluate different locations, which may identify different numbers of patients with enthesitis among SpA subtypes. Thus, the aim of this study was to evaluate whether the proportion of patients with at least one enthesitis across these three most prevalent SpA subtypes differs according to the index used and to evaluate the level of agreement among indices in detecting patients with enthesitis. METHODS: A total of 4185 patients (2719 axSpA, 433 pSpA and 1033 PsA) from the international and cross-sectional ASAS-PerSpA study were included. The proportion of patients with enthesitis identified by the indices was evaluated across the three diseases. Pairwise agreement between indices was computed using Cohen's kappa. RESULTS: The prevalence rates of patients with at least one enthesitis according to the MEI, MASES, SPARCC index and LEI were 17.2%, 13.5%, 10.7%, and 8.3%, respectively. In axSpA, the indices that identified the most patients with enthesitis were the MEI and MASES (98.7% and 82.4%, respectively); in pSpA and PsA, the indices that identified the most patients with enthesitis were the MEI and SPARCC index (MEI: 100% and SPARCC: 84.6%; MEI: 97.3% and SPARCC: 77%, respectively). In the total population, the MASES vs. MEI showed the strongest agreement (absolute agreement 96.3%; kappa: 0.86); similar results were obtained in axSpA patients (97.3%; 0.90). In pSpA and PsA patients, the SPARCC vs. MEI (97.2%; 0.90 and 95.4%; 0.83, respectively) showed the strongest agreement. CONCLUSIONS: These results suggest that the prevalence of patients with enthesitis across SpA subtypes differs depending on the disease and the index used. The MEI and MASES appeared best for assessing enthesis in SpA and axSpA, while the MEI and SPARCC index appeared best for assessing enthesitis in pSpA and PsA.

Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis.

OBJECTIVE: We analyzed NAD+ metabolism in patients with rheumatoid arthritis (RA), its association with disease activity and clinical outcomes of RA, and the therapeutic potential of pharmacologic NAD+ boosting. METHODS: Our study included 253 participants. In the first cohort, comprising 153 RA patients and 56 healthy donors, we assessed NAD+ levels and NAD+ -related gene pathways. We analyzed 92 inflammatory molecules by proximity extension assay. In the second cohort, comprising 44 RA patients starting anti-tumor necrosis factor (anti-TNF) drugs, we evaluated changes in NAD+ levels and their association with clinical response after 3 months. Mechanistic studies were performed ex vivo on peripheral blood mononuclear cells (PBMCs) from patients with RA to test the beneficial effects of NAD+ boosters, such as nicotinamide and nicotinamide riboside. RESULTS: Reduced NAD+ levels were found in RA samples, in line with altered activity and expression of genes involved in NAD+ consumption (sirtuins, poly[ADP-ribose] polymerase, CD38), transport (connexin 43), and biosynthesis (NAMPT, NMNATs). Unsupervised clustering analysis identified a group of RA patients with the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity (as shown by the Disease Activity Score in 28 joints). NAD+ levels were modulated by anti-TNF therapy in parallel with the clinical response. In vitro studies using PBMCs from RA patients showed that nicotinamide riboside and nicotinamide increased NAD+ levels via NAMPT and NMNAT and reduced their prooxidative, proapoptotic, and proinflammatory status. CONCLUSION: RA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti-TNF therapy. The preclinical beneficial effects of NAD+ boosters, as shown in leukocytes from RA patients, along with their proven clinical safety, might pave the way for the development of clinical trials using these compounds.