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BACKGROUND: Evidence on abatacept (ABA) utility for rheumatoid arthritis (RA) - associated interstitial lung disease (ILD) is growing. Clinical trials have shown equivalence in subcutaneous (SC) and intravenous (IV) administration of ABA for articular manifestations. However, this has not been studied in respiratory outcomes. OBJECTIVE: To compare the effectiveness of ABA in RA-ILD patients according to the route of administration. METHODS: National retrospective multicentre study of RA-ILD patients on treatment with ABA. They were divided into 2 groups: a) IV, and b) SC. The following outcomes were analysed from baseline to final follow-up using linear mixed models: a) forced vital capacity (FVC), b) diffusing capacity of the lungs for carbon monoxide (DLCO), c) chest high resolution computed tomography (HRCT), d) dyspnoea, e) RA activity, and f) sparing corticosteroids effect. RESULTS: A total of 397 patients were included (94 IV-ABA and 303 SC-ABA), median follow-up of 24 [10-48] months. After adjustment for possible confounders, FVC and DLCO remained stable during the first 24 months without differences between IV-ABA and SC-ABA (p = 0.6304 and 0.5337). Improvement/ stability of lung lesions in HRCT was observed in 67 % of patients (75 % IV-ABA, 64 % SC-ABA; p = 0.07). Dyspnoea stabilized/ improved in 84 % of patients (90 % IV-ABA, 82 % SC-ABA; p = 0.09). RA - disease activity improved in both groups. No statistically significant differences regarding any of the variables studied between the two groups were found. ABA was withdrawn in 87 patients (21.9 %), 45 % IV-ABA and 37 % SC-ABA (p = 0.29). ILD worsening and articular inefficacy were the most common reasons for ABA discontinuation. CONCLUSION: In patients with RA-ILD, ABA seems to be equally effective regardless of the route of administration.
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BACKGROUND: A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature. METHODS: Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted. RESULTS: Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them. CONCLUSIONS: This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).
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Artérite à cellules géantes , Inhibiteurs des Janus kinases , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Azétidines/usage thérapeutique , Artérite à cellules géantes/traitement médicamenteux , Artérite à cellules géantes/sang , Composés hétérocycliques 3 noyaux , Inhibiteurs des Janus kinases/usage thérapeutique , Pipéridines/usage thérapeutique , Purines/usage thérapeutique , Pyrazoles/usage thérapeutique , Pyrimidines/usage thérapeutique , Récidive , Études rétrospectives , Sulfonamides/usage thérapeutique , Résultat thérapeutiqueRÉSUMÉ
OBJECTIVE: Aortitis in Giant Cell Arteritis (GCA-aortitis) is a frequent complication that may lead to aneurysms. Tocilizumab (TCZ) was approved in GCA, but the efficacy in GCA-aortitis and aneurysms has not been analyzed to date. Our aim was to assess the effectiveness and safety of TCZ in a wide series of GCA-aortitis and aneurysms. METHODS: Multicentre observational study with GCA-aortitis treated with TCZ. GCA was diagnosed by: a) ACR criteria, b) temporal artery biopsy, and/or c) imaging techniques. Aortitis was diagnosed mainly by PET/CT. Main outcomes were EULAR and imaging remission. Others were clinical remission, analytical normalization, corticosteroid-sparing effect, and the prevention and improvement of aneurysms. RESULTS: 196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% reached EULAR remission but only 12% an imaging remission; increasing up-to 81.4% and 31.8%, respectively, at 24 months. A rapid clinical remission, ESR and CRP normalization was observed in 47.4%, 84.3% and 55.6%, at 1 month, increasing to 89.6%, 85.3% and 80.3% at 24 months, respectively. Aneurysms were present in 10 (5%) patients. Five of them required early surgery, while 3 others enlarged. No patient on TCZ therapy developed aneurysms during follow-up. CONCLUSION: In patients with GCA-aortitis treated with TCZ, a rapid and maintained clinical and analytical improvement was observed. However, there was an uncoupling between clinical and EULAR remission with imaging remission.
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OBJECTIVE: This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season. METHODS: We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season. RESULTS: We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80-84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients. CONCLUSIONS: This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year.
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Artérite à cellules géantes , Mâle , Humains , Femelle , Sujet âgé , Sujet âgé de 80 ans ou plus , Artérite à cellules géantes/diagnostic , Incidence , Espagne/épidémiologie , Biopsie , SaisonsRÉSUMÉ
OBJECTIVE: Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT is a promising diagnostic tool for polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV). PET/CT performance is recommended before the onset of steroid therapy because glucocorticoids (GC) may decrease the intensity of FDG uptake. However, this is not always possible in clinical practice. Our aim was to assess if PET/CT could be also useful to detect musculoskeletal and vascular involvement in patients receiving GC. METHODS: Single-center study of patients with PMR diagnosis based on 2012 EULAR/ACR criteria who underwent a PET/CT scan due to LVV suspicion. We compared the musculoskeletal and vascular FDG uptake between two groups: (a) steroid-naïve and (b) steroid-resistant patients. A sub-analysis was conducted in patients who were receiving GC to discern if the cumulative prednisone dose influences the FDG uptake. RESULTS: We evaluated 75 patients (27 men/ 48 women); mean age±SD: 68.2 ± 10.7 years. PET/CT was performed in 14 steroid-naïve and 61 steroid-resistant patients. Patients under GC had received a median cumulative prednisone dose of 1.8 [0.6-3.9] g. The pattern of musculoskeletal FDG uptake was similar in steroid-naïve and steroid-resistant patients. FDG uptake in the vessel wall was more frequently detected in steroid-naïve patients. However, PET/ CT was also useful to detect LVV in 62.3 % of the patients who were receiving GC. The percentage of patients who had positive PET/CT scans tended to decrease with higher cumulative prednisone doses. CONCLUSION: Even though GC therapy may decrease the 18-FDG uptake, PET/CT continues to be a useful tool to detect musculoskeletal and LVV involvement in PMR.
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Fluorodésoxyglucose F18 , Glucocorticoïdes , Rhumatisme inflammatoire des ceintures , Tomographie par émission de positons couplée à la tomodensitométrie , Radiopharmaceutiques , Humains , Rhumatisme inflammatoire des ceintures/traitement médicamenteux , Rhumatisme inflammatoire des ceintures/imagerie diagnostique , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Mâle , Femelle , Sujet âgé , Glucocorticoïdes/administration et posologie , Glucocorticoïdes/usage thérapeutique , Adulte d'âge moyen , Prednisone/usage thérapeutique , Prednisone/administration et posologie , Études rétrospectives , Sujet âgé de 80 ans ou plus , Artérite à cellules géantes/imagerie diagnostique , Artérite à cellules géantes/traitement médicamenteuxRÉSUMÉ
OBJECTIVE: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA. METHODS: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations. RESULTS: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985), and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel-GCA. CONCLUSION: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration, and high ESR reduce the risk of visual involvement.
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INTRODUCTION: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) includes three heterogeneous and difficult to treat clinical entities. Intravenous immunoglobulins (IVIG) may constitute a good therapeutic option, although data hitherto are scarce. The aim of this study was to assess the effectiveness and safety of IVIG in AAV in a real-world setting. METHODS: Single center observational study of patients with AAV with at least one cycle of IVIG since January of 2000 to December of 2020. AAV diagnosis was based on a compatible clinical presentation and positive ANCA serology and/or compatible histology. Disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). The effectiveness was evaluated by clinical and laboratory parameters (CRP, ESR) and its glucocorticoid-sparing effect. These variables were measured at one, six, twelve and twenty-four months of IVIG treatment. The doses of IVIG were 2g/kg in the following cycles of administration: 1 g/kg/day in 2 days (n=12); 0.5 g/kg/day in 4 days (n=11); 0.4 g/kg/day in 5 days (n=5). The clinical improvement was classified according to BVAS categories in remission, partial response and no response. RESULTS: Twenty-eight patients (15 granulomatosis-polyangiitis, 10 microscopic polyangiitis and 3 eosinophilic granulomatosis with polyangiitis) were included. Reasons for using IVIG were relapse/refractory disease (n=25), active or suspected infection (n=3), and both (n=5). We observed a rapid and maintained BVAS score improvement, increasing from 34.6% at 1 month to 56.5% at 2 years of follow-up (p=0.12), and a reduction of glucocorticoids dose. Therapy was well tolerated and adverse events mild and scarce. CONCLUSION: IVIG represents an effective and relative safe therapeutic alternative in relapsing/refractory AAV or in presence of a concomitant active infection.
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Vascularites associées aux anticorps anti-cytoplasme des neutrophiles , Syndrome de Churg-Strauss , Granulomatose avec polyangéite , Humains , Anticorps anti-cytoplasme des polynucléaires neutrophiles , Immunoglobulines par voie veineuse/usage thérapeutique , Granulomatose avec polyangéite/traitement médicamenteux , Granulomatose avec polyangéite/diagnostic , Syndrome de Churg-Strauss/traitement médicamenteux , Vascularites associées aux anticorps anti-cytoplasme des neutrophiles/traitement médicamenteux , Vascularites associées aux anticorps anti-cytoplasme des neutrophiles/diagnosticRÉSUMÉ
INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.
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Syndrome des anticorps antiphospholipides , Lupus érythémateux disséminé , Complications de la grossesse , Naissance prématurée , Rhumatologie , Grossesse , Humains , Nouveau-né , Femelle , Issue de la grossesse/épidémiologie , Naissance prématurée/épidémiologie , Lupus érythémateux disséminé/complications , Lupus érythémateux disséminé/diagnostic , Lupus érythémateux disséminé/traitement médicamenteux , Syndrome des anticorps antiphospholipides/diagnostic , Syndrome des anticorps antiphospholipides/épidémiologie , Syndrome des anticorps antiphospholipides/complications , Complications de la grossesse/épidémiologie , Études rétrospectives , bêta 2-Glycoprotéine I , Anticoagulants , Immunoglobuline G , Immunoglobuline MRÉSUMÉ
OBJECTIVE: Hydroxychloroquine (HCQ) is one of the most used drugs in patients with systemic lupus erythematosus (SLE). In these patients, where heart involvement is common, cardiac HCQ toxicity may lead to fatal outcomes. The aim of this work is to study the influence of cumulative HCQ (cHCQ) in a selected group of patients with SLE and its association with electrocardiographic (EKG) abnormalities. METHODS: Single-center retrospective, observational study in which data were collected from the medical records of consecutive patients with a diagnosis of SLE who started treatment with HCQ and who had a 12-lead EKG before starting treatment and during follow-up. EKG abnormalities were grouped as conduction or structural abnormalities. The association of cHCQ with the occurrence of EKG disturbances was analyzed together with other demographic and clinical variables through univariate and multivariate logistic regression models. RESULTS: 105 patients were selected with median cHCQ of 913 g. The sample was classified into two groups, above or below 913 g. Significantly, more conduction disturbances were observed in the group above the median (OR: 2.89; 95%CI: 1.01-8.23). In the multivariate analysis, the OR per 100 g of cHCQ dose was 1.06 (95%CI: 0.99-1.14). Age was the only variable associated with conduction disturbances. There were no significant differences in the development of structural abnormalities and a tendency for more high-grade atrioventricular block was shown. CONCLUSION: Our study suggests an association between the cHCQ and the development of EKG conduction disturbances that disappears after multivariate adjustment. No increased number of structural abnormalities was observed.
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Antirhumatismaux , Lupus érythémateux disséminé , Humains , Hydroxychloroquine/effets indésirables , Antirhumatismaux/effets indésirables , Études rétrospectives , Lupus érythémateux disséminé/traitement médicamenteux , Lupus érythémateux disséminé/complications , Analyse multifactorielleRÉSUMÉ
INTRODUCTION: Glucocorticoids are associated with serious side effects related to dosing and time of use. Unfortunately, there is no standard method for determining glucocorticoid exposure, especially in patients undergoing long-term treatment. OBJECTIVE: The aim of this work was to create a free and easy-to-use web application to calculate, in a systematic way, the total cumulative dose of corticosteroids. METHODS: The total cumulative dose is calculated as the sum of all periods of treatment with different doses of corticosteroids, and is expressed as the equivalent dose of prednisone in mg. Glucocorticoid doses during periods in which the available information is missing or incomplete are estimated by systematic assumptions. RESULTS: A simulation exercise using standard patterns of steroid use in polymyalgia rheumatica, and giant cell arteritis showed that even when the period of no information reached 50% of the time, the accuracy of the calculator had a mean absolute percentage error (MAPE)<7%. CONCLUSION: This tool simplifies and standardizes the glucocorticoids cumulative dose calculation, thereby minimizing bias in the assessment of glucocorticoid cumulative dose.
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Artérite à cellules géantes , Rhumatisme inflammatoire des ceintures , Humains , Glucocorticoïdes/usage thérapeutique , Prednisone/effets indésirables , Artérite à cellules géantes/traitement médicamenteux , Rhumatisme inflammatoire des ceintures/traitement médicamenteuxRÉSUMÉ
Introduction: Glucocorticoids are associated with serious side effects related to dosing and time of use. Unfortunately, there is no standard method for determining glucocorticoid exposure, especially in patients undergoing long-term treatment. Objective: The aim of this work was to create a free and easy-to-use web application to calculate, in a systematic way, the total cumulative dose of corticosteroids. Methods: The total cumulative dose is calculated as the sum of all periods of treatment with different doses of corticosteroids, and is expressed as the equivalent dose of prednisone in mg. Glucocorticoid doses during periods in which the available information is missing or incomplete are estimated by systematic assumptions. Results: A simulation exercise using standard patterns of steroid use in polymyalgia rheumatica, and giant cell arteritis showed that even when the period of no information reached 50% of the time, the accuracy of the calculator had a mean absolute percentage error (MAPE)<7%. Conclusion: This tool simplifies and standardizes the glucocorticoids cumulative dose calculation, thereby minimizing bias in the assessment of glucocorticoid cumulative dose.(AU)
Introducción: Los glucocorticoides se asocian con efectos secundarios graves, relacionados con dosis y tiempo de uso. Desafortunadamente, no existe un método estándar disponible para determinar el nivel de exposición a glucocorticoides en tratamientos prolongados. Objetivo: Crear una aplicación web gratuita y fácil de usar para calcular, de forma sistematizada, la dosis acumulada de glucocorticoides. Métodos: La dosis acumulada se calcula como la suma de todos los períodos de tratamiento con diferentes dosis, y se expresa como la dosis equivalente de prednisona en mg. La dosis durante los períodos en los que la información no está disponible o está incompleta se estima mediante asunciones sistematizadas. Resultados: Un ejercicio de simulación utilizando patrones estándar de uso de esteroides en la polimialgia reumática y la arteritis de células gigantes demostró que, incluso cuando el período de ausencia de información alcanzaba el 50% del tiempo, la precisión de la calculadora tenía un porcentaje de error medio absoluto (MAPE)<7%. Conclusión: Esta herramienta simplifica y estandariza el cálculo de la dosis acumulativa de glucocorticoides, minimizando el sesgo del cálculo.(AU)
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Dosage , Hormones corticosurrénaliennes , Glucocorticoïdes , Applications mobiles , Rhumatologie , RhumatismesRÉSUMÉ
OBJECTIVES: Tocilizumab (TCZ) is the only biologic therapy approved for giant cell arteritis (GCA). There is general agreement on the initial/maintenance dose, duration of TCZ therapy is not well established. In GiACTA trial, after one year on TCZ, most patients had GCA relapse after withdrawal. The aim of this study is to assess the effectiveness and safety of TCZ therapy optimisation in a large unselected series of patients with GCA in a clinical practice scenario. METHODS: We carried out a multicentre study on 471 GCA patients treated with TCZ. Once prolonged remission was achieved (n=231) and based on a decision between patient and physician, TCZ was optimised (n=125). We compared optimised (TCZOPT) and not optimised (TCZNON-OPT) groups. Prolonged remission defined as normalisation of clinical and laboratory data for 6 months. Optimisation was carried out by decreasing TCZ dose and/or increasing dosing interval. RESULTS: We evaluated 231 GCA patients on TCZ in prolonged remission. At TCZ onset, no differences in demographic, clinical, or laboratory data were observed. First TCZ optimisation was performed after a median follow-up of 12[6-17] months. Intravenous TCZ was optimised from 8 to 4mg/kg/4weeks in 44% patients, while subcutaneous TCZ was optimised from 162mg/w to 162mg/every-other-week in 65% cases. At the end of follow-up, prolonged remission (78.2% vs. 84.2%; p=0.29) and relapses (5.6% vs. 10.4%, p=0.177) were similar in TCZOPT vs. TCZNON-OPT. Severe infections were more frequent in TCZNON-OPT (12.9% vs. 6.6%; p=0.009). CONCLUSIONS: TCZ optimisation may be done once complete remission is achieved by reducing dose or increasing dosing interval. This seems to be effective, safe and cost-effective therapeutic scheme.
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Artérite à cellules géantes , Humains , Artérite à cellules géantes/traitement médicamenteux , Résultat thérapeutique , Anticorps monoclonaux humanisés/effets indésirables , Glucocorticoïdes/usage thérapeutique , RécidiveRÉSUMÉ
Background: Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial. Objective: We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ. Design: This is an observational multicenter study of patients with GCA treated with TCZ. Methods: Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision. Results: Four hundred seventy-one GCA patients (mean age, 74 ± 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL (n = 60; unilateral/bilateral: 48/12), TVL (n = 17; unilateral/bilateral: 11/6), diplopia (n = 2), and blurred vision (n = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved. Conclusion: TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved.
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OBJECTIVE: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. METHODS: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. RESULTS: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. CONCLUSION: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.
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OBJECTIVES: Different Jak inhibitors (jakinibs) have shown efficacy in rheumatoid arthritis (RA), but in a significant proportion of patients, an insufficient response leads to therapy withdrawal. We describe the efficacy and safety of a second jakinib in patients stopping the first due to insufficient response or side effects. METHODS: This is an observational retrospective multicentric study of 31 patients with RA sequentially treated with baricitinib or tofacitinib in any order in clinical practice in ten medical centres in Spain. RESULTS: We identified 31 patients, sequentially treated with both jakinibs. An equal proportion had received tofacitinib or baricitinib first. Most patients (87%) had previously received one or several bDMARD, median 4 (2-5). Median survival for the first jakinib was 5 (3-8) months, and the reasons for withdrawal were inefficacy in 61% and adverse effects in 39%. Most patients (23/31, 74%) maintained the response to the second jakinib after a mean follow-up of 19.5 (12-24) months. In all 8 patients who discontinued the second jakinib, the reason was inefficacy. The treatment suspension rate was similar among patients that had discontinued the first jakinib for inefficacy (26%) or for adverse effects (25%). CONCLUSIONS: Therapy of RA with a second jakinib seems a safe and efficacious option after discontinuation of the first, either for inefficacy or for side effects.
Sujet(s)
Antirhumatismaux , Polyarthrite rhumatoïde , Inhibiteurs des Janus kinases , Antirhumatismaux/effets indésirables , Polyarthrite rhumatoïde/diagnostic , Polyarthrite rhumatoïde/traitement médicamenteux , Humains , Inhibiteurs des Janus kinases/effets indésirables , Études rétrospectives , EspagneRÉSUMÉ
OBJECTIVE: To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) vs combined ABA [ABA plus MTX (ABAMTX) or ABA plus non-MTX conventional synthetic DMARDs (csDMARDs) (ABANON-MTX)] in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was a restrospective multicentre study of RA-ILD Caucasian patients treated with ABA. We analysed in the three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcome variables: (i) dyspnoea; (ii) forced vital capacity (FVC) and diffusion capacity of the lung for the carbon monoxide (DLCO); (iii) chest high-resolution CT (HRCT); (iv) DAS28-ESR; (v) CS-sparing effect; and (vi) ABA retention and side-effects. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the three groups. RESULTS: We studied 263 RA-ILD patients (mean ± s.d. age 64.6 ± 10 years) [ABAMONO (n = 111), ABAMTX (n = 46) and ABANON-MTX (n = 106)]. At baseline, ABAMONO patients were older (67 ± 10 years) and took higher prednisone dose [10 (interquartile range 5-15) mg/day]. At that time, there were no statistically significant differences in sex, seropositivity, ILD patterns, FVC and DLCO, or disease duration. Following treatment, in all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnoea and chest HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in CS-sparing effect in the group on combined ABA (ABAMTX or ABANON-MTX). However, in the multivariable analysis, there were no differences in any outcome variables between the three groups. CONCLUSION: In Caucasian individuals with RA-ILD, ABA in monotherapy or combined with MTX or with other conventional-DMARDs seems to be equally effective and safe. However, a CS-sparing effect is only observed with combined ABA.
Sujet(s)
Abatacept/usage thérapeutique , Polyarthrite rhumatoïde/traitement médicamenteux , Pneumopathies interstitielles/traitement médicamenteux , Méthotrexate/usage thérapeutique , Sujet âgé , Antirhumatismaux/usage thérapeutique , Association de médicaments , Femelle , Humains , Mâle , Adulte d'âge moyen , Études rétrospectivesRÉSUMÉ
Introduction: Secukinumab is a fully human monoclonal antibody which targets and neutralizes interleukin (IL)-17A, a cytokine that plays an important role in the pathophysiology of ankylosing spondylitis (AS). Secukinumab is the first IL-17A inhibitor approved for the treatment of AS.Areas covered: This paper aimed to evaluate the role of IL-17 in human beings, and the blocking of this cytokine with secukinumab while reviewing its efficacy and safety in the treatment of AS from data of MEASURE clinical trials.Expert opinion: MEASURE clinical trials showed efficacy and safety of secukinumab in patients with AS. Mild infections were the most frequent adverse event observed. Mucocutaneous candidiasis was a relatively common side effect due to the role of IL-17A in mucocutaneous defense against extracellular organisms. Secukinumab remained generally well tolerated over the longer-term. The combination of efficacy and safety makes secukinumab a good option of treatment for patients with AS refractory to non-steroidal anti-inflammatory drugs.
Sujet(s)
Anticorps monoclonaux humanisés/effets indésirables , Interleukine-17/immunologie , Pelvispondylite rhumatismale/traitement médicamenteux , Animaux , Anticorps monoclonaux humanisés/administration et posologie , Candidose/induit chimiquement , HumainsRÉSUMÉ
OBJECTIVES: The objective of the present study was to assess the efficacy of apremilast (APR) in the management of refractory oral and/or genital ulcers in patients with Behçet's disease (BD). METHODS: National multicentre open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. RESULTS: We included 51 patients (35 women/16 men; mean age 44.7±13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n=19) or genital (n=2) aphthous ulcers or both (n=30). Other manifestations found at APR onset were arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis induced by TNF-α-inhibitors (n=2), ileitis (n=2), deep venous thrombosis (n=2), leg ulcers (n=1), erythematosus and scaly skin lesions (n=1), fever (n=1), unilateral anterior uveitis (n=1) and neuro Behçet (n=1). After a mean follow-up of 8.5±6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. CONCLUSIONS: APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.
Sujet(s)
Maladie de Behçet , Stomatite aphteuse , Adulte , Maladie de Behçet/complications , Maladie de Behçet/diagnostic , Maladie de Behçet/traitement médicamenteux , Femelle , Humains , Mâle , Adulte d'âge moyen , Thalidomide/effets indésirables , Thalidomide/analogues et dérivés , UlcèreRÉSUMÉ
OBJECTIVES: Digestive involvement (DI) has been reported in 10-30% of primary Sjögren's syndrome (pSS) patients, and few studies have systematically analysed the prevalence of DI in pSS patients. The aim of this study was to describe DI prevalence in pSS patients from the Sjögrenser Study, and to analyse its clinical associations. METHODS: All patients included in the Sjögrenser study, a Spanish multicentre randomised cohort, containing demographic, clinical and histologic data, have been analysed retrospectively. Patients were classified according to the presence of DI (oesophageal, gastric, intestinal, hepatic and pancreatic), and we have performed DI clinical associations, descriptive statistics, Student t or χ2 test, and uni and multivariate logistic regression. RESULTS: From 437 included patients, 95% were women, with a median age of 58 years, 71 (16.2%) presented DI: 21 (29.5%) chronic atrophic gastritis, 12 (16.9%) oesophageal motility dysfunction, 3 (4.2%) lymphocytic colitis, 18 (25.3%) primary biliary cholangitis, 15 (21.1%) autoimmune hepatitis, 7 (9.8%) pancreatic involvement and 5 (7%) coeliac disease. Half of them developed DI at the same time or after pSS diagnosis. Patients with DI were significantly older at pSS diagnosis (p=0.032), more frequently women (p=0.009), presented more autoimmune hypothyroidism and C3 hypocomplementaemia (p=0.040), and were treated more frequently with glucocorticoids, immunosuppressant and biologic therapies. Patients with pancreatic involvement presented more central nervous system and renal involvement, Raynaud's phenomenon, lymphoma and C3/C4 hypocomplementaemia. CONCLUSIONS: DI is frequent in Sjögrenser patients, mainly in the form of autoimmune disorders, and seem to be associated with a more severe phenotype. Our results suggest that DI should be evaluated in pSS patients, especially those with more severe disease.
Sujet(s)
Hépatite auto-immune , Syndrome de Gougerot-Sjögren , Études de cohortes , Femelle , Humains , Mâle , Adulte d'âge moyen , Essais contrôlés randomisés comme sujet , Enregistrements , Études rétrospectives , Syndrome de Gougerot-Sjögren/complications , Syndrome de Gougerot-Sjögren/diagnostic , Syndrome de Gougerot-Sjögren/épidémiologieRÉSUMÉ
This study aimed at determining socio-demographic and clinical factors of primary Sjögren syndrome (pSS) associated with osteoporosis (OP) and fragility fracture. SJOGRENSER is a cross-sectional study of patients with pSS, classified according to American European consensus criteria developed in 33 Spanish rheumatology departments. Epidemiological, clinical, serological and treatment data were collected and a descriptive analysis was conducted. Bivariate and multivariate analyses were performed using a binomial logistic regression to study the factors associated with OP and fragility fracture in pSS. 437 patients were included (95% women, with a median age of 58.6 years). 300 women were menopausal (76.4%). Prevalence of OP was 18.5% [in men (N = 21) this measured 19%]. A total of 37 fragility fractures were recorded. In the multivariate analysis, there was an association between OP and age: in the 51-64 age range (menopausal women), the OR measured 9.993 (95% CI 2301-43,399, p = 0.002); In the age > 64 years group, OR was 20.610 (4.679-90.774, p < 0.001); between OP and disease duration, OR was 1.046 (1.008-1085, p = 0.017); past treatment with corticosteroids, OR 2.548 (1.271-5.105, p = 0.008). Similarly, an association was found between fragility fractures and age: in the 51-64 age group, OR measured 5.068 (1.117-22,995, p = 0.035), age > 64 years, OR was 7.674 (1.675-35,151, p < 0.009); disease duration, OR 1.049 (CI 1.003-1097, p < 0.036) and the ESSDAI index, OR 1.080 (1.029-1134, p = 0.002). Patients with pSS can develop osteoporosis and fragility fractures over the course of the disease. Age, corticosteroids treatment and disease duration were associated with the development of OP. Disease duration and ESSDAI were associated with the development of fractures in patients with pSS.