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Background: The EXXELERATE study revealed poorer clinical outcomes in patients treated with adalimumab (ADL) and baseline rheumatoid factor (RF) above 203 IU/mL. However, responses were similar in patients treated with certolizumab pegol (CZP) regardless of RF levels., Objectives: This study investigated the impact of RF levels >203 IU/mL on TNF inhibitors (TNFi) serum levels and the association with secondary nonresponse in RA patients treated with TNFi., Methods: We performed an observational ambispective study with RA patients treated with infliximab (IFX), ADL, or CZP. Patients were stratified according to baseline RF levels: ≤ or >203 IU/mL. After 6 months, serum drug levels and antidrug antibodies were measured, and reasons for discontinuation were collected., Results: We included 170 RA patients: 90 (53%) received IFX, 48 (28%) ADL, and 32 (19%) CZP. While CZP serum levels did not differ between RF groups at 6 months ( p  = 0.6), RF levels >203 IU/mL were linked to lower serum drug levels in patients treated with IFX ( p  = 0.09) or ADL ( p  = 0.02). Secondary nonresponse was 3.6 times higher in patients with high versus low RF levels in patients under IFX or ADL. However, the reasons for withdrawal were not affected by RF levels in patients treated with CZP., Conclusion: Baseline RF above 203 IU/mL is associated with lower serum drug levels and an increased risk of discontinuation due to secondary nonresponse in patients treated with IFX or ADL. In contrast, drug levels and clinical outcomes are not significantly impacted by baseline RF levels in patients under CZP., Competing Interests: CP-R has received research grants/honoraria from AbbVie, Pfizer, Novartis, Lilly, and Roche. MN-N has received research grants/honoraria from Galápagos, Janssen, Lilly, Novartis, and UCB. AB received grant/research support and fees for consultancies or as a speaker from AbbVie, Amgen, Pfizer, Novartis, BMS, Nordic, Sanofi, Sandoz, Lilly, UCB, and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Plasencia-Rodríguez, Martínez-Feito, Novella-Navarro, Pérez De Diego, Bonilla, Gehin, Villalba-Yllán, Nuño, Pascual-Salcedo, Nozal, Almirón and Balsa.)

Objectives: To evaluate the survival of different biologic or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling difficult-to-treat rheumatoid arthritis (D2TRA) criteria, and to assess factors related to treatment discontinuation., Methods: Retrospective study including D2TRA patients. Drug retention of the b/tsDMARD administered after fulfilling D2TRA was assessed by Kaplan-Meier plots and the log-rank test. Cox hazard models were used to identify factors affecting treatment discontinuation., Results: Of the 122 patients included, 75 maintained active treatment (61.5%) with a subsequent line after D2T compared to 47 (38.5%) who discontinued and required more successive lines of b/tsDMARDs. The median survival of the treatments was 78.3(7.6) months and the treatment after D2T with the better rate of survival was rituximab, followed by JAKi and IL6Ri, while worse survival rates were associated with abatacept and TNFi. Significant differences were noted among b/tsDMARDs (log-rank p < 0.01) and to evaluate these differences, a Cox regression was performed, taking each b/tsDMARD as a reference and comparing it with the others. DAS28 values 6-months after initiation of treatment were higher in those patients who discontinued treatment [4.4(1.2) vs 3.5(1.3), p = 0.01]. The multivariate cox regression model revealed that treatment choice after D2T [HR = 1.26(95%CI 1.06-1.05)] and lower DAS28 values at 6 months [HR = 1.49(95%CI 1.16-1.52)] were independent risk factors associated with treatment discontinuation., Conclusions: Once patients met the D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival rates were rituximab, JAKi and IL6Ri. Moreover, DAS28 at 6-months of treatment after D2T was an independent risk factor for drug discontinuation. Key Points • Rituximab, IL6Ri and JAKi have better retention rates in patients after fulfilling D2TRA criteria • Clinical disease activity in the first six months after fulfillment of D2TRA criteria is an independent risk factor of subsequent treatment survival., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: A subset of human circulating FoxP3+ regulatory T cells expresses CD39 (cTreg39+) and hydrolyses pro-inflammatory adenine nucleotides released at inflammatory foci, rendering the anti-inflammatory agent adenosine. Methotrexate (MTX), inhibiting ATIC, enhances the extrusion of adenine nucleotides and may help Treg39+ cells control inflammation. Therefore, we examined the relation of cTreg39+ cells with the effect of MTX in early Rheumatoid Arthritis (eRA)., Methods: Freshly isolated peripheral blood lymphocytes from 98 untreated eRA patients and 98 healthy controls (HC) were examined by cytometry. Twelve months (12m) after initiating MTX, 82 patients were clinically re-evaluated and cytometry was repeated in 40 of them. The effect of MTX on Treg cell potency was assessed in Treg/Tresp cocultures., Results: The baseline (0m) cTreg39+ cell frequency was elevated in eRA above HC levels. Patients who reached low disease activity at 12 months (12m-LDA, DAS28-ESR≤ 3.2, n = 51) had presented with a significantly higher 0m cTreg39+ frequency vs those who did not (n = 31). The 0m cTreg39+ cutoff for attaining 12 m-LDA was 42.0% (Sensitivity=90.4%/Specificity=96.8%). At 12m, the cTreg39+ frequency was no longer elevated but its association with disease activity remained: it was still significantly higher in patients who had reached LDA vs those who had not. In vitro, MTX augmented the Treg39+ cell potency but had no effect on Treg39- cells., Conclusion: MTX cooperates with Treg39+ cells and the baseline cTreg39+ frequency predicts the response to MTX in eRA. In addition, the transiently elevated baseline cTreg39+ frequency in eRA may provide a slot for prompt MTX initiation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate whether hypoechoic wall thickness is influenced by the systole or diastole moment in the cardiac cycle and if this can influence ultrasound (US) assessments of giant cell arteritis (GCA)., Methods: US videos of 100 consecutive patients (50 with GCA, 50 without) performed between January 2021 and June 2023 were reviewed. Intima-media thickness (IMT) of temporal (including common trunk, frontal and parietal branches), axillary and subclavian arteries were measured at two different time points, at systolic peak (SP) and at the end-diastole (ED). Differences between SP IMT and ED IMT, as well as in the halo count (HC) and in the OMERACT GCA Ultrasonography Score (OGUS) between these two times, were analyzed., Results: IMT was significantly higher (4.8-5%) at ED in all arteries, in both GCA and non-GCA groups. HC and OGUS were also higher in ED in both groups. In 4 non-GCA patients (8%), the HC was positive in ED and negative in SP; in all of them the HC in ED was 1. In the GCA group, the timing of the cardiac cycle did not influence the final US diagnosis; however, it did modify the HC in 14 patients (28%)., Conclusion: IMT can fluctuate during the cardiac cycle, with higher measurements occurring at ED. This variability could potentially impact the accuracy of US diagnoses and assessments of GCA. If further research corroborates these findings, it may be imperative to revise the guidelines for employing US in diagnosing GCA in order to incorporate these nuanced aspects., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Certolizumab pegol (CZP), an Fc-free antibody fragment, has shown stable serum levels and steady efficacy in the treatment of RA patients, irrespective of RF levels at baseline. Here, we examine, in clinical practice, the effect of baseline RF and ACPA levels on serum drug levels of IFX, ADL and CZP an Fc-free antibody fragment., Methods: This is a retrospective study performed in real-world patients. We assessed 170 patients with RA: 90 (53%) received IFX, 48 (28%) ADL and 32 (19%) CZP. Demographic and clinical variables, RF and ACPA levels were obtained at the baseline visit (T0), and patients were stratified based on negative, low, medium, or high levels. After 6 months (T6) serum drug levels and anti-drug antibodies (ADAb), were computed., Results: While CZP serum levels did not differ across RF groups at T6, high baseline RF was linked to lower serum drug levels compared to RF negative status in treatment with complete monoclonal antibodies IFX and ADL. No differences in disease activity measured by DAS28 at baseline were observed across RF quartiles in patients treated with IFX or ADL. ADAb was observed in 26 patients with IFX, 3 with ADL and 1 with CZP, following 6 months of treatment. Patients with high baseline RF levels dropped out more frequently by secondary non-response in IFX or ADL than CZP (80% vs. 75% vs. 33%, p=0.002)., Conclusions: In this real word data evaluation, CZP serum levels were independent of RF levels in patients however patients with high baseline RF levels who obtained IFX or ADL had lower serum drug levels at 6 months than baseline RF-negative patients. In addition, secondary non-response was more frequent in patients with high RF levels treated with IFX and ADL.

Background: Rheumatic and musculoskeletal diseases (RMDs) are chronic diseases that may alternate between asymptomatic periods and flares. These conditions require complex treatments and close monitoring by rheumatologists to mitigate their effects and improve the patient's quality of life. Often, delays in outpatient consultations or the patient's difficulties in keeping appointments make such close follow-up challenging. For this reason, it is very important to have open communication between patients and health professionals. In this context, implementing telemonitoring in the field of rheumatology has great potential, as it can facilitate the close monitoring of patients with RMDs. The use of these tools helps patients self-manage certain aspects of their disease. This could result in fewer visits to emergency departments and consultations, as well as enable better therapeutic compliance and identification of issues that would otherwise go unnoticed., Objective: The main objective of this study is to evaluate the implementation of a hybrid care model called the mixed attention model (MAM) in clinical practice and determine whether its implementation improves clinical outcomes compared to conventional follow-up., Methods: This is a multicenter prospective observational study involving 360 patients with rheumatoid arthritis (RA) and spondylarthritis (SpA) from 5 Spanish hospitals. The patients will be followed up by the MAM protocol, which is a care model that incorporates a digital tool consisting of a mobile app that patients can use at home and professionals can review asynchronously to detect incidents and follow patients' clinical evolution between face-to-face visits. Another group of patients, whose follow-up will be conducted in accordance with a traditional face-to-face care model, will be assessed as the control group. Sociodemographic characteristics, treatments, laboratory parameters, assessment of tender and swollen joints, visual analog scale for pain, and electronic patient-reported outcome (ePRO) reports will be collected for all participants. In the MAM group, these items will be self-assessed via both the mobile app and during face-to-face visits with the rheumatologist, who will do the same for patients included in the traditional care model. The patients will be able to report any incidence related to their disease or treatment through the mobile app., Results: Participant recruitment began in March 2024 and will continue until December 2024. The follow-up period will be extended by 12 months for all patients. Data collection and analysis are scheduled for completion in December 2025., Conclusions: This paper aims to provide a detailed description of the development and implementation of a digital solution, specifically an MAM. The goal is to achieve significant economic and psychosocial impact within our health care system by enhancing control over RMDs., Trial Registration: ClinicalTrials.gov NCT06273306; https://clinicaltrials.gov/ct2/show/NCT06273306., International Registered Report Identifier (irrid): PRR1-10.2196/55829., (©Marta Novella-Navarro, Jose M Iniesta-Chamorro, Diego Benavent, Javier Bachiller-Corral, Enrique Calvo-Aranda, Helena Borrell, Laura Berbel-Arcobé, Victoria Navarro-Compan, Xabier Michelena, Leticia Lojo-Oliveira, Jaime Arroyo-Palomo, Mariana Diaz-Almiron, Verónica García García, Irene Monjo-Henry, Claudia María Gómez González, Enrique J Gomez, Alejandro Balsa, Chamaida Plasencia-Rodríguez. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 22.04.2024.)

Objectives: To investigate the appearance of anti-drug antibodies (ADA) against infliximab (IFX) determined by drug-sensitive and drug-tolerant assays and their relationship with drug levels and drug survival., Methods: This longitudinal observational study included 45 patients with rheumatoid arthritis (RA) and 61 with spondyloarthritis (SpA). Serum samples were obtained at weeks 2, 6, 12, 24, and 52. Serum IFX levels were measured by a capture enzyme-linked immunosorbent assay (ELISA) and ADA by an in-house drug-sensitive two-site (bridging) enzyme-linked immunosorbent assay (bELISA) and a commercially available drug-tolerant ELISA (IDK, Immundiagnostik, Germany)., Results: Anti-drug antibodies were detected earlier by IDK than by bELISA. Once ADA appeared, positivity persisted throughout the study period. Patients who were bELISA ADA+ had higher IDK ADA levels (than bELISA ADA- patients). Circulating IFX levels were detected in all patients except those found to be bELISA ADA+. Serum IFX levels were lower in IDK ADA+ than in IDK ADA-patients.Most patients (64%) discontinued due to inefficacy. The early onset of immunogenicity was related to IFX survival. Both in RA and SpA, the median survival (years) was shorter in patients with earlier development of ADA (IDK+ before or at week 24) than those who became IDK+ later (after week 24) or never developed ADA., Conclusion: A drug-tolerant assay detects ADA during IFX therapy earlier and more frequently than a drug-sensitive assay. The onset of immunogenicity detected by drug-tolerant assays is related to the subsequent detection of ADA by drug-sensitive assays and drug survival., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction: Rheumatoid arthritis (RA) is a heterogeneous disease in which therapeutic strategies used have evolved dramatically. Despite significant progress in treatment strategies such as the development of anti-TNF drugs, it is still not possible to differentiate those patients who will respond from who will not. This can lead to effective-treatment delays and unnecessary costs. The aim of this study was to utilize a profile of the patient's characteristics, clinical parameters, immune status (cytokine profile) and artificial intelligence to assess the feasibility of developing a tool that could allow us to predict which patients will respond to treatment with anti-TNF drugs., Methods: This study included 38 patients with RA from the RA-Paz cohort. Clinical activity was measured at baseline and after 6 months of treatment. The cytokines measured before the start of anti-TNF treatment were IL-1, IL-12, IL-10, IL-2, IL-4, IFNg, TNFa, and IL-6. Statistical analyses were performed using the Wilcoxon-Rank-Sum Test and the Benjamini-Hochberg method. The predictive model viability was explored using the 5-fold cross-validation scheme in order to train the logistic regression models., Results: Statistically significant differences were found in parameters such as IL-6, IL-2, CRP and DAS-ESR. The predictive model performed to an acceptable level in correctly classifying patients (ROC-AUC 0.804167 to 0.891667), suggesting that it would be possible to develop a clinical classification tool., Conclusions: Using a combination of parameters such as IL-6, IL-2, CRP and DAS-ESR, it was possible to develop a predictive model that can acceptably discriminate between remitters and non-remitters. However, this model needs to be replicated in a larger cohort to confirm these findings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: To analyse the trajectories of Disease Activity Score 28 (DAS28), patient global assessment (PGA) and physician global assessment (PhGA) and to assess their predictive capabilities on difficult-to-treat rheumatoid arthritis (D2TRA) classification., Methods: Longitudinal study of patients with rheumatoid arthritis (RA) from 2020 to 2022. Based on the D2TRA EULAR (European Alliance of Associations for Rheumatology) definition, patients were classified as D2TRA according to biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) failure due to inefficacy (D2TRA-inefficacy) or other reasons (D2TRA-other). Patients who did not fulfil the D2TRA criteria were classified as NoD2TRA. DAS28, PGA and PhGA scores collected every 6 months during the first 24 months of b/tsDMARD treatment were used to identify different trajectories using latent class mixed models (LCMM)., Results: The study population comprised 255 patients with RA, of whom 167 were NoD2TRA, 58 D2TRA-inefficacy and 30 D2TRA-other. LCMM stratified patients into two different trajectories for DAS28 and PhGA and three for PGA according to the most stable model. The most notable variation occurred during the first 6 months of treatment, thereafter remaining stable during the follow-up period. Most D2TRA-inefficacy patients fitted the trajectory, showing higher values of the studied parameters. NoD2TRA followed the trajectory with lower values, and D2TRA-other were distributed more homogeneously across all trajectories., Conclusions: The assessment of disease activity, together with patients' and physicians' perceptions, form a key element in the correct discrimination of patients who are going to develop D2TRA-inefficacy. However, identifying those patients who will be D2TRA-other remains challenging, whether by subjective or objective parameters., Competing Interests: Competing interests: MNN reports grants from UCB, Lilly, Galapagos and Janssen outside the submitted work. AV reports grants from Janssen. IM reports grants from Roche, Novartis, UCB and Gedeon Richter outside the submitted work. CP-R reports grants from AbbVie, Pfizer, Novartis, Lilly and Roche outside the submitted work. AB reports grants from AbbVie, Amgen, Pfizer, Galapagos, Novartis, Gilead, BMS, Nordic, Sanofi, Sandoz, Lilly, UCB and Roche outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The study aims to evaluate the utility of major salivary gland ultrasonography for diagnosis of primary Sjögren's syndrome (pSS) and to assess its concordance with minor salivary gland biopsy (MSGB)., Methods: A cross-sectional study of 72 patients with suspected pSS was performed. Demographic, clinical, and serological data were collected. MSGB was performed, as was ultrasonography. The ultrasound technician was blind to clinical, serological, and histological data. The validity of ultrasonography compared with MSGB, the American-European Consensus Group (AECG), and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria was assessed by calculating the percentage of agreement, sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC)., Results: Based on MSGB as the gold standard, the percentage of agreement between both tests was 78% (AUC 0.75). Based on the ACR/EULAR criteria, the percentage of agreement was 83% (AUC 0.78) for ultrasonography and 81% (AUC 0.83) for biopsy. Sensitivity and specificity were 90% and 67%, respectively, for ultrasonography and 76% and 90% for biopsy. The results were similar with the AECG criteria. The intra- and inter-observer variability was good (κ > 0.7). Significant differences were observed for positive anti-Ro52 values and hypergammaglobulinemia in pathological ultrasound scans., Conclusion: Diagnostic ultrasonography is as useful as MSGB in pSS. Therefore, it could be included in the classification criteria. In this cohort, it proved more sensitive than MSGB and could be used as an initial test for patients suspected of having pSS. MSGB could be used in cases where clinical and serological results are inconclusive. Key Points • Major salivary gland ultrasonography adds diagnostic value similar to that of MSGB, thus potentially enabling this invasive procedure to be avoided. • Ultrasonography could be included in the classification criteria for primary Sjögren's syndrome. • Given that ultrasonography is more sensitive and less specific than MSGB, it could be used as an initial diagnostic test in patients with suspected Sjögren's syndrome. • Biopsy should be performed in those cases where ultrasonography, clinical, and serological data are inconclusive., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Real world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients., Material and Methods: This is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4-6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack., Results: A total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17-163) in patients vs 625 (405-932) in controls, p < 0.001). Patients treated with rituximab had lower Ab levels than those treated with TNFi and controls (p < 0.001). The cellular response to SARS-CoV-2 vaccine was evaluated in 30 patients. Eleven patients had a positive cellular response, being more frequent in patients treated with rituximab (p = 0.03). SARS-CoV-2 infection was reported in 43% of patients and 34% of controls after vaccination. Only 6 (7%) patients required hospitalization, most of whom treated with rituximab (67%)., Conclusion: SARS-CoV-2 antibody levels were lower in patients than in controls, especially in patients treated with rituximab. A cellular response can be detected despite having a poor humoral response. Severe infections in vaccinated patients with IMIDs are rare, and are observed mainly in patients treated with rituximab., (© 2023. Canadian Society of Allergy & Clinical Immunology.)

Objectives: Multiple failures to biologic or targeted specific disease-modifying anti-rheumatic drugs (b/tsDMARDs) that lead to difficult-to-treat rheumatoid arthritis (D2TRA) may be the result of multi-drug inefficacy or reflect treatment problems related to adverse events, comorbidities, and/or poor adherence. We aimed to characterise a cohort of D2TRA patients in clinical practice, to analyse the differences between D2TRA due to inefficacy versus D2TRA from other causes, and to compare them with non-D2TRA., Methods: The D2TRA group included patients who were receiving ≥2b/tsDMARDs due to inefficacy (D2TRA-inef cacy) or because of adverse events, poor adherence, contraindications, comorbidities, drug-intolerance, etc. (D2TRA-other). Patients who achieved low disease activity or remission with the rst bDMARD were classified as non-D2TRA patients. For all patients, demographic, clinical characteristics and laboratory parameters were assessed prior to starting the rst b/tsDMARD. Descriptive analysis was performed and bivariate logistic regression models were assembled., Results: In total, 253 patients were included: 131 non-D2TRA and 122 D2TRA [86 (70.5%) D2TRA-inefficacy and 36 (29.5%) D2TRA-other]. Comparison of the two groups of D2TRA patients: no differences in gender, age at start of b/tsDMARD or age at RA diagnosis were found; this was also true of socioeconomic status, frequency of anxiety-depression and other comorbidities. Patients categorised as D2TRA-other had less extra-articular manifestations than D2TRA-inef cacy, as well as lower values of DAS28 at the start of the rst b/tsDMARD. Comparisons of Non-D2TRA patients versus D2TRA-other resulted in the following observations: no differences in sociodemographic characteristics were evident nor were there any differences in terms of disease activity., Conclusions: Patients with D2TRA-other are indistinguishable from non-D2TRA patients at baseline, indicating the former cohort does not appear to have any predictive value during the early stages of b/tsDMARD treatment, unlike what occurs in patients with D2TRA-inefficacy.

Objectives: Most studies on difficult-to-treat rheumatoid arthritis (D2T RA) have focused on established RA. Here, we analyse whether disease activity in the early stages of RA could influence progression to a D2T RA under real-life conditions. Other clinical and treatment-related factors were also analysed., Methods: A longitudinal multicentre study of patients with RA was conducted from 2009 to 2018. Patients were followed up until January 2021. D2T RA was defined based on EULAR criteria (treatment failure, signs suggestive of currently active/progressive disease and management being perceived as problematic by the rheumatologist and/or patient). The main variable was disease activity in the early stages. The covariates were sociodemographic, clinical and treatment-related factors. We ran a multivariable logistic regression analysis to investigate risk factors associated with progression to D2T RA., Results: The study population comprised 631 patients and 35 (5.87%) developed D2T RA. At the time of diagnosis, the D2T RA group were younger, with a higher disability, 28-joint Disease Activity Score (DAS28) score, tender joint count and pain scores. In our final model, DAS28 was not statistically significantly associated with D2T RA. No differences were found between groups for therapy. Disability was independently associated with D2T RA (OR: 1.89; p=0.01)., Conclusions: In this cohort of patients newly diagnosed with RA, our results do not allow us to prove the influence of active disease according to DAS28. However, we did find that younger patients and those with elevated initial disability scores are more likely to develop D2T RA regardless of other factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)