Visual manifestations in giant cell arteritis: identification of risk factors from the ARTESER Registry.

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.

Biologic therapy in refractory neurobehçet's disease: a multicentre study of 41 patients and literature review.

OBJECTIVES: To assess efficacy and safety of biologic therapy (BT) in neurobehçet's disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug. METHODS: Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters. RESULTS: We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30-60) mg/day at the initial visit to 5 (3.8-10) mg/day after 6 months (P < 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)-15.3 (11.9) mm/1st h, P = 0.011] and median (IQR) C-reactive protein [1.4 (0.2-12.8) to 0.3 (0.1-3) mg/dl, P = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment. CONCLUSIONS: BT appears to be effective and relatively safe in refractory NBD.

Abatacept in monotherapy vs combined in interstitial lung disease of rheumatoid arthritis-multicentre study of 263 Caucasian patients.

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.

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients.

OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.

Abatacept in usual and in non-specific interstitial pneumonia associated with rheumatoid arthritis.

OBJECTIVE: To compare the effectiveness of abatacept (ABA) in Rheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD) according to the radiological patterns of usual (UIP) or non-specific interstitial pneumonia (NSIP). METHODS: From an observational longitudinal multicentre study of 263 RA-ILD patients treated with ABA, those with UIP or NSIP were selected. Lung function, chest high resolution computerised tomography (HRCT) and dyspnoea were recorded and compared in both groups from baseline to the end of follow-up (progression definitions: improvement or worsening >10% of FVC or DLCO, changes in HRCT extension and 1-point change in the mMRC scale, respectively). Differences between final and baseline visits were calculated as the average difference (95% CI) through mixed effects models regression. RESULTS: We studied 190 patients with UIP (n=106) and NSIP (n=84). General features were similar in both groups except for older age, positive rheumatoid factor, and previous sulfasalazine therapy, which were more frequent in patients with UIP. ILD duration up to ABA initiation was relatively short: median 16 [4-50] and 11 [2-36] months (p=0.36) in UIP and NSIP, respectively. Mean baseline FVC and DLCO were 82% and 63% in UIP and 89% and 65% in NSIP, respectively. Both parameters remained stable during 24 months with ABA. HRCT lesions and dyspnoea improved/stabilized in 73.1% and 90.5% and 72.9% and 94.6% of UIP and NSIP patterns, respectively. CONCLUSION: ABA seems equally effective in stabilizing dyspnoea, lung function and radiological impairment in both UIP and NSIP patterns of RA-ILD. Early administration of ABA may prevent RA-ILD progression, regardless of the radiological pattern.

18F-FDG-PET/CT Scan for Detection of Large Vessel Involvement in Giant Cell Arteritis: Arteser Spanish Registry.

Background/Objectives: Imaging studies have transformed the diagnosis of large vessel vasculitis (LVV) involvement in giant cell arteritis (GCA). A positron emission tomography/computed tomography (PET/CT) scan with 18-fluorodeoxyglucose (18F-FDG) has emerged as a valuable tool for assessing LVV. We aimed to determine the utility of an 18F-FDG-PET/CT scan in detecting LVV in GCA in the ARTESER registry. Methods: The ARTESER study is a large multicenter, retrospective, longitudinal, and observational study, promoted by the Spanish Society of Rheumatology. It included patients newly diagnosed with GCA across 26 tertiary hospitals from 1 June 2013 to 29 March 2019. Patients with a diagnosis of incidental GCA were included if they fulfilled specific criteria, including the ACR 1990 criteria, positive imaging examinations, or the expert clinical opinion of investigators. Differences between patients with positive and negative 18F-FDG-PET/CT scan results were analyzed using a bivariate model. A regression model assessed associations in patients with a positive scan, and the predictive capacity of the cumulative dose of glucocorticoids (GC) on PET scan outcomes was evaluated using ROC curve analysis. Results: Out of 1675 GCA patients included in the registry, 377 met the inclusion criteria of having an 18F-FDG-PET/CT scan. The majority were diagnosed with a cranial GCA phenotype, and 65% had LVV. The thoracic aorta was the most frequently affected. Cardiovascular disease, diabetes, and older age had a negative association with a positive scan outcome. The OR for having a positive 18F-FDG-PET/CTC scan was lower as the number of days increased. Depending on the cumulative dosage of the GC, the 18F-FDG-PET/CT scan showed an AUC of 0.74, with a Youden index > 60 mg/day. Conclusions: Younger patients showed a higher probability of presenting LVV as detected by the 18F-FDG-PET/CT scan. The timing of the examination and the cumulative dosage of the GC influenced the likelihood of a positive result, with earlier tests being more likely to detect inflammation.

Subcutaneous vs intravenous abatacept in rheumatoid arthritis-interstitial lung disease. National multicentre study of 397 patients.

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.

Treatment With Tofacitinib in Refractory Psoriatic Arthritis: A National Multicenter Study of the First 87 Patients in Clinical Practice.

OBJECTIVE: Tofacitinib (TOF) is the first Janus kinase (JAK) inhibitor approved for psoriatic arthritis (PsA). It has shown efficacy in patients refractory to anti-tumor necrosis factor-α in randomized controlled trials (RCTs). Our aim was to assess efficacy and safety of TOF in clinical practice. METHODS: This was an observational, open-label multicenter study of PsA patients treated with TOF due to inefficacy or adverse events of previous therapies. Outcome variables were efficacy, corticosteroid dose-sparing effect, retention rate, and safety. A comparative study of clinical features between our cohort of patients and those from the OPAL Beyond trial was performed. RESULTS: There were 87 patients (28 women/59 men), with a mean age of 52.8 ± 11.4 years. All patients were refractory to biologic disease-modifying antirheumatic drugs (DMARDs) and/or to conventional synthetic DMARDs plus apremilast. TOF was started at 5 mg twice daily after a mean follow-up of 12.3 ± 9.3 years from PsA diagnosis. At first month, Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) decreased from median 4.8 (IQR 4.1-5.4) to 3.7 (IQR 2.8-4.7, P < 0.01), Disease Activity Index for Psoriatic Arthritis from median 28 (IQR 18.4-34.1) to 15.5 (IQR 10.1-25.7, P < 0.01), and C-reactive protein from median 1.9 (IQR 0.3-5.0) to 0.5 (IQR 0.1-2.2) mg/dL (P < 0.01). Also, TOF led to a significant reduction in prednisone dose. Mild adverse effects were reported in 21 patients (24.13%), mainly gastrointestinal symptoms. TOF retention rate at Month 6 was 77% (95% CI 65.2-86.3). Patients in clinical practice were older with longer disease duration and received biologic agents more commonly than those in the OPAL Beyond trial. CONCLUSION: Data from clinical practice confirm that TOF seems to be effective, rapid, and relatively safe in refractory PsA despite clinical differences with patients in RCTs.