Subsequent biologic and targeted synthetic disease modifying anti rheumatic drugs after fulfilling difficult-to-treat rheumatoid arthritis criteria: a survival analysis.

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.

The influence of the cardiac cycle on the halo sign and its impact on the ultrasound diagnosis of giant cell arteritis.

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 OMERACT Giant cell arteritis Ultrasonography Score: a potential predictive outcome to assess the risk of relapse during follow-up.

OBJECTIVE: To determine whether the OMERACT giant cell arteritis (GCA) Ultrasonography (US) Score (OGUS) change after treatment can be used for assessing the probability of relapse. METHODS: Multicenter retrospective study of GCA patients referred to two US GCA fast-track clinics over 2 years. Patients underwent US evaluation at baseline, 3 and 6 months. EULAR definitions for remission and relapse were checked at 3 and 6 months. OGUS changes at 0-3 months and 0-6 months were compared among patients with and without relapse at 6 months, as well as those with and without remission at 6 months. RESULTS: A total of 76 patients were included (mean age 77.2 years, 55.3% females). Nineteen (26%) patients relapsed at 6-months, of whom 14(19.1%) showed a minor relapse. EULAR remission at 6 months was achieved by 32(43.8%) patients. The standardized mean difference of OGUS between baseline and 3 and 6 months was -0.25 and -0.38, respectively. OGUS significantly improved between baseline and 6 months (1.18 vs 0.99,p=0.004) and from 3-6 months (1.08 vs 0.99,p=0.04) in non-relapsing patients, whereas no significant changes at 3 (1.17 vs 1.17;p=0.736) and 6 (1.17 vs 1.21;p=0.343) months were observed in those who experienced relapse. Mean 0-6-month OGUS improvement was lower in patients who relapsed (-0.1 vs 0.16,p=0.037). Mean 0-6-month OGUS improvement was greater in patients who achieved remission at 6 months (0.28vs -0.07,p=0.001). CONCLUSIONS: The absence of OGUS improvement during follow-up in GCA may be used to assess the probability of relapse and the absence of remission at 6 months.

Toward Telemonitoring in Immune-Mediated Inflammatory Diseases: Protocol for a Mixed Attention Model Study.

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.

Circulating Tfh cells are differentially modified by abatacept or TNF blockers, and predict treatment response in Rheumatoid Arthritis.

OBJECTIVE: CD4+CXCR5+PD-1hi follicular helper T (Tfh) cells dwell in the germinal centers (GCs) of lymphoid organs and participate in Rheumatoid Arthritis (RA) pathogenesis; the frequency of their circulating counterparts (cTfh-frequency) is expanded in RA and correlates with the pool of GC Tfh cells. Our objective was to study the effect of abatacept (ABT) or TNF blockers (TNFb) on the cTfh-frequency in RA. METHODS: Peripheral blood was drawn from seropositive-longstanding RA patients chronically receiving csDMARDS (n = 45), TNFb (n = 59), or ABT (n = 34), and healthy controls (HC) (n = 137). Also, patients with an incomplete response to csDMARDS (n = 41) who initiated TNFb (n = 19) or ABT (n = 22), were studied at 0 and 12 months. The cTfh-frequency was examined by cytometry. RESULTS: As compared with HC, an increased cTfh-frequency was seen in seropositive-longstanding RA chronically receiving csDMARDs or TNFb but not ABT. After escalating from csDMARDs, the cTfh-frequency did not vary in patients who were given TNFb but decreased to HC levels in those given ABT. In the ABT group, the baseline cTfh-frequency was higher for patients who attained 12M remission (12Mr), vs those who remained active (12Ma): 0m cutoff for remission >0.38% (Sens. 92%, Sp. 90%), OR 25.3. Conversely, in the TNFb group, the baseline cTfh-frequency was lower for 12Mr vs 12Ma: 0m cutoff for non-remission >0.44% (Sens. 67%, Sp. 90%), OR 8.5. CONCLUSION: ABT but not TNFb, is able to curtail the cTfh-frequency in RA. A higher baseline cTfh-frequency predicts a good response to ABT but a poor response to TNFb.

Influence of rheumatoid factor on serum drug levels of TNF inhibitors with different structures in rheumatoid arthritis.

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.