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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.
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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.
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OBJECTIVE: The main objective of this study was to analyse the prevalence and characteristics of subclinical GCA in patients with PMR. METHODS: This was a cross-sectional multicentre international study of consecutive patients with newly diagnosed PMR without symptoms or signs suggestive of GCA. All patients underwent US of the temporal superficial, common carotid, subclavian and axillary arteries. Patients with halo signs in at least one examined artery were considered to have subclinical GCA. The clinical, demographic and laboratory characteristics of the PMR group without subclinical vasculitis were compared with subclinical GCA, and the pattern of vessel involvement was compared with that of a classical single-centre GCA cohort. RESULTS: We included 346 PMR patients, 267 (77.2%) without subclinical GCA and 79 (22.8%) with subclinical GCA. The PMR patients with subclinical GCA were significantly older, had a longer duration of morning stiffness and more frequently reported hip pain than PMR without subclinical GCA. PMR with subclinical GCA showed a predominant extracranial large vessel pattern of vasculitic involvement compared with classical GCA, where the cranial phenotype predominated. The patients with PMR in the classical GCA group showed a pattern of vessel involvement similar to classical GCA without PMR but different from PMR with subclinical involvement. CONCLUSION: More than a fifth of the pure PMR patients had US findings consistent with subclinical GCA. This specific subset of patients showed a predilection for extracranial artery involvement. The optimal screening strategy to assess the presence of vasculitis in PMR remains to be determined.
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Arteritis de Células Gigantes , Polimialgia Reumática , Humanos , Arteritis de Células Gigantes/epidemiología , Arteritis de Células Gigantes/diagnóstico , Polimialgia Reumática/epidemiología , Polimialgia Reumática/diagnóstico , Prevalencia , Estudios Transversales , DolorRESUMEN
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.
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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.
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Antirreumáticos , Artritis Reumatoide , Certolizumab Pegol , Factor Reumatoide , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Artritis Reumatoide/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factor Reumatoide/sangre , Certolizumab Pegol/uso terapéutico , Certolizumab Pegol/sangre , Anciano , Antirreumáticos/uso terapéutico , Antirreumáticos/sangre , Resultado del Tratamiento , Anticuerpos Antiproteína Citrulinada/sangre , Adulto , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/sangre , Infliximab/sangre , Infliximab/uso terapéutico , Infliximab/inmunología , Monitoreo de Drogas/métodos , Biomarcadores/sangre , Factores de TiempoRESUMEN
OBJECTIVES: To describe the frequency and causes for the presence of a halo sign on the ultrasound of patients without a diagnosis of GCA. METHODS: In total, 305 patients with temporal artery colour Doppler ultrasound showing the presence of halo sign (intima-media thickness ≥0.34 mm for temporal arteries [TAs] and ≥1 mm for axillary arteries) were included, and their medical records were reviewed. The clinical diagnosis based on the evolution of the patient over at least one year was established as the definitive diagnosis. RESULTS: Fourteen of the 305 (4.6%) patients included showed presence of the halo sign without final diagnosis of GCA: 12 patients in the TAs (86%), and two patients with isolated AAs involvement (14%). Their diagnoses were PMR (n = 4, 29%); atherosclerosis (n = 3, 21%); and non-Hodgkin lymphoma type T, osteomyelitis of the skull base, primary amyloidosis associated with multiple myeloma, granulomatosis with polyangiitis, neurosyphilis, urinary sepsis and narrow-angle glaucoma (n = 1 each, 7%). CONCLUSION: The percentage of halo signs on the ultrasound of patients without GCA is low, but it does exist. There are conditions that may also show the halo sign (true positive halo sign), and we must know these and always correlate the ultrasound findings with the patient's clinic records.
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Grosor Intima-Media Carotídeo/estadística & datos numéricos , Arteritis de Células Gigantes/diagnóstico por imagen , Ultrasonografía Doppler en Color/estadística & datos numéricos , Anciano , Reacciones Falso Positivas , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Arterias Temporales/diagnóstico por imagenRESUMEN
OBJECTIVES: To assess the validity of Doppler ultrasound in the diagnosis of giant cell arteritis (GCA), using the American College of Rheumatology (ACR) criteria and biopsy and using as gold standard the patient's definitive clinical diagnosis. METHODS: An observational, descriptive and analytical study of 451 consecutive patients with suspected GCA was conducted, and the clinical history and ultrasound findings of the patients were reviewed. The validity of ACR criteria, temporal arteritis biopsy (TAB) and Doppler ultrasound in the diagnosis of GCA was calculated using the final diagnosis of the doctor in charge as the gold standard. RESULTS: The validity and security of the diagnostic tests used were as follows: ACR criteria had 65.37% sensitivity and 62.89% specificity; positive predictive value [PPV] 70%; negative predictive value [NPV] 57.82%, likelihood ratio [LR] + 1.7619 and LR - 0.5506. Doppler ultrasonography had 91.60% sensitivity and 95.83% specificity; PPV 96.62%; NPV 89.76%, LR + 21.81 and LR - 0.0876; TA biopsy 42.86% sensitivity and 100% specificity; PPV 100%; NPV 35.71% and LR - 0.5714. CONCLUSIONS: The halo sign, especially if bilateral, is a strong predictor of GCA with a level of accuracy sufficient to recommend its introduction into clinical practice and, in our opinion, should be considered in future classification criteria sets.
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Arteritis de Células Gigantes/diagnóstico por imagen , Arterias Temporales/diagnóstico por imagen , Ultrasonografía Doppler en Color , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Arteritis de Células Gigantes/patología , Humanos , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Arterias Temporales/patologíaRESUMEN
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.
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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.
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Telemedicina , Humanos , Telemedicina/métodos , Estudios Prospectivos , Artritis Reumatoide/inmunología , Artritis Reumatoide/terapia , España , Masculino , FemeninoRESUMEN
OBJECTIVE: To determine the diagnostic discriminant validity between large vessel giant cell arteritis (LV-GCA) and atherosclerosis using ultrasound (US) intima-media thickness (IMT) measurements. METHODS: We included 44 patients with LV-GCA and 42 with high-risk atherosclerosis. US examinations of the axillary, subclavian, and common carotid arteries (CCA) were systematically performed using a MylabX8 system (Genoa, Italy) with a 4-15-MHz probe. IMT ≥ 1 mm was accepted as pathological. RESULTS: The LV-GCA cohort included 24 females and 20 males with a mean age of 72.8 ± 7.6 years. The atherosclerosis group included 25 males and 17 females with a mean age of 70.8 ± 6.5 years. The mean IMT values of all arteries included were significantly higher in LV-GCA than in atherosclerosis. Among LV-GCA patients, IMT ≥ 1 mm was seen in 31 axillary, 30 subclavian, and 28 CCA. In the atherosclerotic cohort, 17 (38.6%) had IMT ≥ 1 mm with axillary involvement in 2 patients, subclavian in 3 patients, carotid distal in 14 patients (5 bilateral), and isolated carotid proximal affectation in 1 case. A cutoff point greater than 1 pathological vessel in the summative count of axillary and subclavian arteries or at least 3 vessels in the count of six vessels, including CCA, showed a precision upper 95% for GCA diagnosis. CONCLUSION: The IMT is higher in LV-GCA than in atherosclerosis. The proposed US halo count achieves an accuracy of > 95% for the differential diagnosis between LV-GCA and atherosclerosis. The axillary and subclavian arteries have higher discriminatory power, while carotid involvement is less specific in the differential diagnosis.
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Aterosclerosis , Arteritis de Células Gigantes , Masculino , Femenino , Humanos , Anciano , Anciano de 80 o más Años , Persona de Mediana Edad , Arteritis de Células Gigantes/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Diagnóstico Diferencial , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología , Aterosclerosis/diagnóstico por imagen , Arterias Temporales/patologíaRESUMEN
OBJECTIVE: To determine the impact of ultrasound (US) intrinsic limitation to assess aortitis versus FDG-PET/CT in patients with US-proven giant cell arteritis (GCA) and to identify factors associated with aortic involvement. METHODS: Retrospective observational study of patients referred to US fast-track clinics at two academic centres over a 4-year period. Only patients with GCA confirmed by US were included. Temporal arteries (TA) and extracranial arteries US were performed at baseline. FDG-PET/CT was performed according to clinician's criteria. An FDG artery uptake at the aorta higher than liver uptake was considered positive for aortitis. RESULTS: Seventy-two of 186 patients with US-proven GCA underwent an FDG-PET/CT; 29 (40.3%) had a positive FDG-PET/CT and 24 (33.3%) presented aortitis. Only 6 (20.7%) patients with positive FDG-PET/CT had negative US findings of large vessel (LV)-GCA. Among patients with aortitis in FDG-PET/CT, only two (8.3%) had negative US findings of LV-GCA. Patients with aortitis were younger (68.9 vs 81;p<0.001), more frequently females (79.2% vs 39.6%;p=0.002) and had higher platelets count (413.4 vs 311.1;p=0014). Patients with aortitis presented positive TA US less frequently (41.7% vs 83.3%;p<0.001), but more LV US involvement (91.7% vs 41.7%; p<0.001) versus patients without aortitis. None of the patients with aortitis exhibited visual symptoms (0% vs 31.2%;p=0.001). CONCLUSIONS: FDG-PET/CT can detect aortitis in one out of every three patients with US-proven GCA. However, a negative US examination for LV-GCA suggests a low risk of aortitis. Younger and female GCA patients with thrombocytosis, absence of visual manifestations and LV-GCA on US may more frequently present aortitis by FDG-PET/CT.
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Aortitis , Arteritis de Células Gigantes , Humanos , Femenino , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/diagnóstico , Aortitis/diagnóstico por imagen , Aortitis/etiología , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , UltrasonografíaRESUMEN
AIMS: First, to compare clinical features and biological disease modifying anti-rheumatic drugs (bDMARDs) response in patients with axial spondyloarthritis (axSpA) and axial psoriatic arthritis (axPsA). Second, to identify possible predictors of treatment response in both entities. METHODS: One-year follow-up, observational, single-center study including all patients with axSpA or axPsA who started bDMARDs therapy. Clinical features were collected at baseline while disease activity was measured at baseline, 6 and 12 months by the Ankylosing Spondylitis Disease Activity Score and the Physician Global Assessment. The frequency of patients achieving inactive disease (ID), low disease activity (LDA), high or very high disease activity and clinical improvement were compared between axSpA and axPsA. Baseline predictor factors for achieving treatment response were identified through regression models, using odds ratio (OR) as an estimate. RESULTS: In total, 352 patients were included: 287 (81.5%) axSpA and 65 (18.5%) axPsA. No significant differences at baseline were observed between the two diseases for most of the characteristics. While HLA-B27 positivity was associated with axSpA (OR = 5.4; p < 0.001), peripheral manifestations were associated with axPsA (OR = 4.7; p < 0.001). The frequency of patients with axSpA and axPsA achieving ID/LDA after 6 and 12 months of bDMARDs was comparable: 53% versus 58%, p = 0.5; and 58% versus 60%, p = 0.9, respectively. Both diseases also presented similar clinical improvement. In axSpA and axPsA, male gender seemed to be associated with achieving LDA [OR at 12 months visit = 2.8 (p < 0.01) and 2.7 (p = 0.09)]. CONCLUSION: In clinical practice, patients with axSpA and axPsA present numerous similarities, including comparable medium-term clinical response to bDMARDs. Male gender could be a predictor of treatment response in both diseases.Keyword: axial spondyloarthritis, psoriatic arthritis, axial involvement, clinical characteristics.
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BACKGROUND: Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians. OBJECTIVES: This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure. METHODS: This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients). RESULTS: A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34-26.82) were independently associated with being MR-patients to bDMARDs. CONCLUSIONS: In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Terapia Biológica , Preescolar , Humanos , Estudios Longitudinales , Estudios Prospectivos , Calidad de VidaRESUMEN
OBJECTIVES: Analyse clinical and bone metabolism features in a case series of patients with multiple vertebral fractures after discontinuation of denosumab (DMab). METHODS: An observational descriptive study analysing data from ten patients with multiple vertebral fractures after DMab discontinuation that were admitted to our rheumatology department between 2015 and 2018. RESULTS: There were a total of 49 spontaneous fractures after an average of 6 DMab doses and 10.9 months from discontinuation. Ninety percent had already received treatment other than DMab 7 of 10 oral bisphosphonates. After discontinuation, CTX and P1NP remained elevated and mean T-score for femoral neck and lumbar spine was lower than before treatment. The most affected vertebrae were L3, L5, D6, D7, D9 and D11. CONCLUSION: This report of ten new cases suffering multiple vertebral fractures early after discontinuation of DMab highlights the emerging concern on the subject in the scientific community and the need to clarify its pathogenic mechanism, and to support by solid evidence the new recommendations on its management.
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Conservadores de la Densidad Ósea/administración & dosificación , Denosumab/administración & dosificación , Fracturas Múltiples/etiología , Fracturas de la Columna Vertebral/etiología , Privación de Tratamiento , Anciano , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Our objective was to study the frequency of circulating CD19+CD24hiCD38hi B cells (Breg) in AS patients. To this end, peripheral blood was drawn from AS patients naïve for TNF blockers (AS/nb) (n = 42) and healthy controls (HC) (n = 42). Six patients donated blood for a second time, 6 months after initiating treatment with anti-TNFα drugs. After isolation by Ficoll-Hypaque, PBMCs were stained with antibodies to CD3, CD4, CD19, CD24, and CD38, and examined by cytometry. For functional studies, total CD19+ B cells were isolated from PBMCs of 3 HC by magnetical sorting. Breg-depleted CD19+ B cells were obtained after CD19+CD24hiCD38hi B cells were removed from total CD19+ cells by cytometry. Total CD19+ B cells or Breg-depleted CD19+ B cells were established in culture and stimulated through their BCR. Secretion of IFNγ was determined by ELISA in culture supernatants. When compared with HC, AS/nb patients demonstrated a significantly increased frequency of Breg cells, which was independent of disease activity. Anti-TNFα drugs induced a significant reduction of circulating Breg numbers, which were no longer elevated after six months of treatment. Functional in vitro studies showed that the secretion of IFNγ was significantly higher in Breg-depleted as compared with total CD19+ B cells, indicating that Breg can downmodulate B cell pro-inflammatory cytokine secretion. In summary, an increased frequency of circulating CD19+CD24hiCD38hi B cells is observed in AS/nb patients, that is not related with disease activity; anti-TNFα drugs are able to downmodulate circulating Breg numbers in AS.