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Backgroundgiant cell arteritis (gca) is a systemic vasculitis that affects large vessels, with a higher incidence in patients aged 70 years. It is known that GCA involves temporal arteries and the aorta and its branches either concomitantly or in isolation. Differentiating the characteristics in the expression of these disease subtypes will be relevant for the initial treatment, prognosis and the follow up.ObjectivesTo analyze the different clinical and laboratory between the patterns of GCA involvement.MethodsRetrospective study of new consecutive patients diagnosed with GCA for four years. 90.9% were diagnosed by Color Doppler ultrasound, measuring the superficial temporal arteries, common trunk, their frontal and parietal branches, and the extracranial arteries (axillary, subclavian, and carotid arteries). 9.1% were diagnosed by PET-CT or temporal artery biopsy. Ultrasound diagnosis was according to the OMERACT definitions of the halo sign and an intima-media cut off a thickness of ≥0.34 mm for the temporal arteries, ≥0.42 in the common superficial temporal artery and ≥ 1 mm for the axillary, subclavian, and carotid arteries. Clinical records were reviewed and their demographic, clinical and laboratory data were compared between patterns of ultrasound involvement. The EULAR recommendations of 2018 [1] were used to the remission and relapse.ResultsA total of 163 patients were included, 50.3% women, with a mean age of 79 years. Regarding the GCA subtypes, 78 patients had exclusive involvement of cranial arteries (CGCA), 36 patients had isolated involvement of extracranial giant cell arteritis (LVGCA) and 49 patients had mixed forms with both cranial and extracranial involvement (MGCA) Table 1.The analysis showed that patients with LVGCA present constitutional syndrome more frequently, less anterior Ischemic optic neuropathy (AION) (p<0.001) and less ESR values (p<0.01) than patients with CGCA. Extracranial artery involvement in any of the subtypes showed a significant association with polymyalgia rheumatica (PMR), although this was not exclusive to LVGCA. CGCA was associated with more AION-type ischemic manifestations than LVGCA. Remission maintained for at least 6 months together with corticosteroid-free remission is higher in LVGCA. No statistically significant differences in relapses, both major and minor.Table 1.Clinical and laboratory characteristics between GCA subtypesGCA 163CGCA 78LVGCA 36MGCA 49CGCA -MGCA pCGCA -LVGCA pLVGCA - MGCA pFemale sex, n (%)82 (50.3)41 (52.6)21 (58.3)20 (40.8)0.3780.5650.134Age years, mean ± SD79 ± 7.879 ± 7.577.6 ± 1079.2 ± 6.70.8830.4350.403ESR, mm/h mean ± SD57 ± 3463 ± 37.342.2 ± 27.647.4 ± 350.0190.0030.467CRP mg/dL mean ± S.D.52.6 ± 5454 ± 55.443.2 ± 5649.4 ± 49.40.6310.3350.588PMR, n (%)88 (53.6)32 (41)23 (63.9)33 (66)0.0050.0230.839Constitutional symptoms, n (%)87 (53)38 (48.7)25 (69.4)24 (48)0.9360.0380.047AION, n (%)38 (23)25 (32)3 (8.3)10 (20)0.1350.0060.136Remission 6 months, n (%)45 (27.4)14 (17.9)15 (41.7)16 (32)0.0570.0060.393Glucocorticoid free-remission, n (%)28 (17)8 (10.3)9 (25)11 (22)0.0680.0390.745Major relapse, n (%)7 (4.2)3 (3.8)3 (8.3)1 (2)0.9470.6790.751Minor relapse, n (%)52 (31.7)25 (32)11 (30.6)16 (32)0.9430.9470.378CGCA Cranial giant cell arteritis; LVGCA Large vessel giant cell arteritis; MGCA Mixed giant cell arteritis; SD standard deviation; AION anterior Ischemic optic neuropathy; PMR polymyalgia rheumatica; CRP C reactive protein; ESR erythrocyte sedimentation rate.ConclusionClinical features are different between the different GCA patterns. Patients with LVGCA have a greater constitutional syndrome and lower ESR than patients with CGCA. CGCA was associated with more NOIA-type ischemic manifestations than LVGCA. PMR is more frequent in cases with large vessel involvement. There is more maintained and corticosteroid-free remission in patients with LVGCA.Reference[1]Hellmich B., et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020; 79:19–30Acknowledgements:NIL.Disclosure of InterestsMariela del Carmen Uyaguari Morocho: None declared, Elisa Fernández-Fernández: None declared, Irene Monjo Speakers bureau: Roche, Novartis, UCB, Gedeon, Richter, Consultant of: Roche, Eugenio de Miguel Speakers bureau: AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grünenthal, Janssen, Sanofi, Paid instructor for: Janssen, Novartis, Roche, Consultant of: AbbVie, Novartis, Pfizer, Galapagos, Grant/research support from: AbbVie, Novartis, Pfizer.

BackgroundIn the last few years, several cut-off points for the intima-media thickness (IMT) of temporal arteries (TA) and large vessels (LV) have been proposed for the ultrasound (US) diagnosis of giant cell arteritis (GCA). It has usually been recommended to use the average measure of the higher IMT, but there is currently a lack of consensus on this. We have observed some changes in the IMT measurements depending of if they are performed in systole or diastole.ObjectivesThe main objective of this study is to confirm if there are differences in the IMT measurement taken in systole or diastole and if they are clinically relevant.MethodsObservational retrospective study on consecutive patients of our GCA fast track clinic. The gold standard diagnosis was the opinion of the clinical doctor after at least 6 months of follow-up. US recorded videos, of every explored vessel temporal (common trunk, frontal and parietal branches), subclavian and axillary arteries were reviewed and the IMT of each of them was measured in systole and diastole peaks for comparison. We define an ultrasound result as positive with cut-off values of IMT ≥ 0.34 mm for frontal and parietal branches, ≥ 0.42 mm for the common trunks of TA, and ≥ 1 mm for the axillary and subclavian arteries. Demographic data of the included patients were also collected.ResultsWe have included 72 cases, 36 with GCA diagnosis and 36 without GCA (controls). The mean values of age and sex, as well as the IMT in systole and diastole of each vessel are shown in Table 1. There were not significant differences in sex but patients without GCA were younger (p<0.01).The US IMT measurements at the systolic and diastolic times showed statistically significant differences in all the explored vessels, as in patients with GCA as in the control non GCA group. All the IMT measured in diastole showed higher and statistically significant values than those measured in systole, with a mean increment of measurement of 5.3% and 6.5% in TA and 6.4% and 5.6% in LV, respectively in the GCA and control group.This result can be of clinical relevance because if we used diastolic measures, instead of systolic measures, 5/36 (13.8%) cases in controls had halo sign in one isolated vessel (2 cases in parietal right, 1 in common trunk right, 1 in subclavian right, 1 in subclavian left). However, in GCA patients, the number of patients with halo sign did not change, but the number of pathological vessels was increased when the measured was performed in diastole (1 frontal right branch, 1 common trunk right, 4 frontal left branches, 5 common trunks left and 2 axillary right), so this could have influence in the assessment of the disease.ConclusionThere are significant differences between the IMT measured in systolic and diastolic peaks, with higher values in diastole. The differences are relatively small but may increase the number of false positives (13.8%) in controls, and the number of affected vessels in the GCA group. This should be considered in the diagnosis and assessment of GCA.Table 1.Changes in the IMT values in systole and diastole in GCA and non GCA patientsCategoryNo GCAGCAN3636Sex ♂ / ♀ (n)14/2217/19Age years (mean ± SD)74.4±9.480.8±6.6SystoleDiastolepSystoleDiastolepTA Frontal (right)0.23±0.560.24±0.600.0010.36±0.150.39±0.160.001TA Frontal (left)0.21±0.440.23±0.460.0010.37±0.180.39±0.180.010TA Parietal (right)0.21±0.400.23±0.410.0010.42±0.210.44±0.210.001TA Parietal (left)0.21±0.450.23±0.430.0010.38±0.200.40±0.210.001TA Common (right)0.25±0.760.26±0.740.0010.48±0.260.52±0.280.001TA Common (left)0.23±0.500.23±0.500.0010.44±0.200.44±0.200.001Axillary (right)0.57±0.140.60±0.140.0010.76±0.300.82±0.290.001Axillary (left)0.54±0.130.57±0.130.0010.72±0.290.76±0.320.010Subclavian (right)0.64±0.150.68±0.150.0010.79±0.270.85±0.300.001Subclavian (left)0.61±0.160.64±0.160.0010.80±0.330.85±0.340.001GCA= giant cell arteritis; N= number of patients; SD= standard deviation; TA temporal artery. Measures are showed in mm.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

The 2022 ACR/EULAR giant cell arteritis (GCA) classification criteria have been designed to improve diagnostic accuracy incorporating vascular imaging modalities and potential large vessel (LV) involvement. These new criteria have been validated in an independent set of patients and controls, with a sensitivity of 87.0% and a specificity of 94.8%, but not tested in routine care. Our objective is to examine the performance of the new 2022 ACR/EULAR GCA classification criteria in this clinical scenario. Multicentric retrospective observational study of patients referred to our ultrasound (US) fast track clinic over a 4-year period. The gold standard for GCA diagnosis was clinical confirmation after 6 months of follow-up. Patients with GCA were compared with unselected controls referred to our clinic with suspected GCA. All patients underwent US exam of temporal and extracranial arteries (carotid, subclavian and axillary) within 24-48 hours at baseline. FDG-PET/CT was performed according to standard clinician criteria. Following the new 2022 GCA ACR/EULAR classification criteria, the total score for the 10 items included in the criteria was calculated, with a total cut-off ≥ 6 for the classification of GCA. The performance of these criteria was evaluated in all GCA patients across different subsets of the disease. A total of 319 patients (188 cases and 131 controls) were included for analysis (mean age 76 years, 58.9% females). Patients with GCA and controls differed in age (78.2 vs 72.9, p<0.001) and sex (females 53.2% vs 67.2%, p=0.013). The diagnostic accuracy of the 2022 ACR/EULAR GCA classification criteria and the previous 1990 ACR GCA classification criteria in different subsets of patients is shown in Table 1. Overall, the new criteria had a sensitivity of 92.6% and a specificity of 74%, using GCA clinical diagnosis as an external criterion and the area under the curve (AUC) was 0.932 (95% CI 0.903 to 0.960). Isolated LV-GCA showed a sensitivity of 62.2% and a specificity of 74% (AUC 0.696 [0.596 – 0.796]) and biopsy-proven GCA showed a sensitivity of 100% and a specificity of 74% (AUC 0.992 [0.981 – 1]). The new 2022 ACR/EULAR GCA classification criteria showed good diagnostic accuracy of patients with suspected GCA under routine care, and a substantial improvement upon the sensitivity and specificity of the 1990 ACR GCA classification criteria in all patients subsets. NIL. NIL. None Declared. Table 1Diagnostic accuracy of the new 2022 ACR/EULAR GCA and the 1990 ACR/EULAR classification criteria, with clinical diagnosis serving as the external criteria in all GCA, patients with isolated cranial GCA, isolated LV-GCA, all LV-GCA and biopsy proven GCA. GCA, giant cell arteritis; LV, large vessel; Sens, sensitivity; Spec, specificity; LR+, positive likelihood ratio; LR−, negative likelihood ratio; AUC: area under the ROC curve analysisSensSpecLR+LR-AUC (95% CI)All GCA (n = 188) vs controls (n = 131)2022 ACR/EULAR criteria92.6%74%3.560.10.932 (0.903 – 0.960)1990 ACR criteria53.2%80.2%2.680.580.719 (0.663 – 0.775)Isolated cranial GCA (n = 83) vs controls (n = 131)2022 ACR/EULAR criteria96.4%74%3.710.050.965 (0.933 – 0.996)1990 ACR criteria61.4%80.2%3.10.480.764 (0.699 – 0.829)Isolated LV-GCA (n = 37) vs controls (n = 131)2022 ACR/EULAR criteria62.2%74%2.390.510.696 (0.596 – 0.796)1990 ACR criteria18.9%80.2%0.951.010.554 (0.455 – 0.653)Biopsy proven GCA (n = 21) vs controls (n = 131)2022 ACR/EULAR criteria100%74%3.8500.992 (0.981 – 1)1990 ACR criteria95.2%80.2%4.810.060.931 (0.877 – 0.985)LV-GCA (with or without cranial GCA) (n = 105) vs control (n=131)2022 ACR/EULAR criteria89.5%74%3.440.140.905 (0.865 – 0.946)1990 ACR criteria46.7%80.2%2.360.660.683 (0.616 – 0.751)

The EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice suggest the performance of diagnostic imaging tests in all patients with suspected GCA and ultrasound is the recommended first-line test in patients with suspected cranial GCA (c-GCA)1. However, a priority imaging modality has not been established in cases of suspected GCA involving large vessels (LV-GCA). Since patients with LV-GCA often undergo extensive screening programs for suspected infection or malignancy before the diagnosis of GCA is established, our knowledge in this field needs to be improved. The aim of this study is to investigate the wall affectation of vasculitis of the proximal arm and neck arteries in patients with suspected GCA, polymyalgia rheumatica (PMR), atherosclerosis and non-GCA patients. Retrospective available ultrasound examination from all the patients referred to our GCA fast-track clinic in the last three years were collected. All patients had ultrasound of cranial and large vessel examination (axillary, subclavian and carotid arteries). GCA diagnosis was confirmed by the doctor after a follow-up between six months to three years. Every patient had videos and pictures of every referred vessel. Examination was performed by two rheumatologists with long experience in GCA ultrasound from the same Rheumatology Department with a Esaote Mylab Twice with probe of 13 MHz (2017-2019) and a Esaote Mylab X8plus with a probe of 15 MHz (2019-2020). IMT and hypoechoic halo measures were taken. We analyzed 300 examinations and selected 196 baseline cases of four different pathologies (29 PMR, 40 atherosclerosis, 71 GCA of which 14 LV-GCA without cranial involvement and 56 non-GCA non-PMR controls). Intima-media thickness (IMT) with the statistical significance between different diseases and controls are showed in the Table 1. GCA ultrasound of large vessels shows significant differences with other diseases. The differences seem to support the use of ultrasound in the fast-track clinic of GCA not only in c-GCA but also in LV-GCA. [1]Dejaco C et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis. 2018 May;77(5):636-643. doi: 10.1136/annrheumdis-2017-212649. Epub 2018 Jan 22. PMID: 29358285. Iñigo González-Mazón: None declared, Elisa Fernández-Fernández: None declared, Irene Monjo Speakers bureau: Roche, Novartis, UCB, Gedeon Richter, Consultant of: Roche, Eugenio de Miguel Speakers bureau: AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi., Paid instructor for: Janssen, Novartis, Roche, Consultant of: AbbVie, Novartis, Pfizer, Galapagos, Grant/research support from: Abbvie, Novartis, Pfizer Table 1Ultrasound IMT and halo measures in large vessels of different diseases and controlsNon-GCA n=56GCA n=71Atherosclerosis n=40PMR n=29LV-GCAn=14Axillary right # *0.67±.190.95±0.300.70±0.180.65±0.131.03±0.33Axillary left # **0.61±0.120.92±0.290.72±0.190.66±0.130.99±0.25Subclavian right # *0.70±0.151.00±0.310.86±0.290.70±0.201.09±0.36Subclavian left # *0.62±0.140.95±0.270.70±0.140.64±0.181.05±0.25CCD right #0.79±0.220.97±0.261.01±0.300.81±0.100.91±0.29CCD left #0.81±0.160.99±0.220.98±0.320.82±0.200.97±0.17GCA= Giant cell arteritis (cranial, large vessel and mixed forms); Non-GCA = Patients suspected but not confirmed as GCA; Atherosclerosis = patients with high arteriosclerosis risk without suspected GCA; PMR = Patients with polymyalgia rheumatica without GCA; LV-GCA= Large vessel vasculitis GCA without cranial involvement.# p<0.01 GCA vs non-GCA and GCA vs PMR* p<0.01 GCA vs Atherosclerosis; ** p<0.05 GCA vs Atherosclerosis

At denosumab discontinuation, an antiresorptive agent is indicated to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report two cases of postmenopausal women, previously exposed to bisphosphonates, treated with alendronate at denosumab discontinuation. Alendronate was ineffective to avoid spontaneous clinical vertebral fractures. They presented three and nine spontaneous vertebral fractures 8 and 12 months after denosumab discontinuation, respectively. Ineffectiveness of alendronate was attributed to insufficient control of the rebound as assessed by B-crosslaps measures in the first case, and partially to the high risk of fractures in the later. In both situations, the increased fracture risk may have favoured these new fractures. It is urgent to define effective therapeutic strategies to avoid spontaneous vertebral fractures after denosumab discontinuation.

Background Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase–ALP–measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. Results Forty subjects ( 47%) had a variant(s) in ALPL . With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9–30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9–13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p  < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p  < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. Conclusions In subjects with persistent hypophosphatasaemia –secondary causes excluded– one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variant.

BackgroundDespite pharmacological options for axial spondyloarthritis (axSpA) have increased recently, still one out of three patients do not achieve the recommended target [1].ObjectivesTo determine patient and disease characteristics in patients with “difficult to treat” (D2T) axSpA in comparison with “good responders” (GR) and to identify predictive factors of D2T-axSpA.MethodsData from an observational prospective cohort recruiting consecutively patients diagnosed of axSpA initiating the first bDMARD from La Paz Hospital between 2004-2019 were analysed. Patients who fulfilled one of the following definitions were included: i) D2T: failure to at least two b/tsDMARDs, ii) GR: patients remaining treated with the first bDMARD for at least 3 years or stopping it due to disease control. Clinical characteristics, laboratory tests, concomitant treatment and disease activity measures prior to starting the first bDMARD and after 6 months were collected. Also, b/tsDMARD courses were registered. Chi-square or Fisher test were used for qualitative variables and unpaired t-student was used for quantitative variables. Univariable and multivariable logistic binary regression analyses were used.ResultsOut of 101 patients included, 41.6% were classified as D2T and 58.4% as GR. When initiating the first bDMARD, compared with GR, D2T patients had statistically significant shorter symptom duration and more frequently enthesitis, inflammatory bowel disease (IBD), concomitant NSAIDs, smoking habit and comorbidities (hypertension, dyslipidemia, depression or anxiety and fibromyalgia), all p<0.05 (Table 1). However, no significant differences were found in age, sex, BMI, subtype of axSpA, dactylitis, peripheral arthritis, uveitis, psoriasis, concomitant csDMARDs, diabetes mellitus or cardiopathy. While no differences were found for disease activity composite measures (ASDAS, BASDAI) and CRP or ESR, D2T patients had greater scores in BASDAI questions for pain and morning stiffness, TJC, PtGA and PhyGA. After 6 months of starting the first bDMARD, the scores for all disease activity measures, including ASDAS, BASDAI, CRP and ESR were significantly higher in D2T patients. Reasons for b/tsDMARDs discontinuation in D2T patients are shown in Figure 1. In multivariable analysis, smoking habit (OR=6.5, p<0.05), HLAB27 negative (OR=5.8, p<0.05), enthesitis (OR=48.1, p<0.01), baseline TJC (OR=1.2, OR<0.05) and baseline PhyGA (OR=1.05, p<0.05) were independently associated with D2T.ConclusionCompared with GR, patients with D2T-axSpA have more frequently poor prognostic factors for therapy response (smoking and HLAB27 negative) and worse response to first bDMARD after 6 months. Further strategies to implement recommendations for not smoking and control of comorbidities should be implemented.Reference[1]Smolen JS, et al. Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Ann Rheum Dis. 2018.Table 1.Stratified characteristics. Results are shown as absolute numbers (%) or mean ± standard deviation.GR (n=59)D2T (n=42)p valueSymptom duration until first bDMARD (year)10.5±10.75.5±7.7<0.01Current smoking habit7 (11.9)13 (31)<0.05HLAB27 +48 (82.8)27 (64.3)<0.05Enthesitis35 (59.3)40 (95.2)<0.001IBD2 (3.4)6 (14.3)<0.05ComorbiditiesHypertension15 (25.4)20 (47.6)<0.05Dyslipidemia23 (39)28 (66.7)<0.01Depression or anxiety14 (23.7)23 (54.8)<0.01Fibromyalgia1 (1.7)6 (14.3)<0.05Concomitant NSAIDs43 (81.1)35 (97.2)<0.05BaselineASDAS3.3±13.6±0.90.2BASDAI5.6±2.16.4±1.70.06BASDAI-spinal pain6.4±2.77.5±2.1<0.05BASDAI-stiffness severity5.9±2.87.1±2.5<0.05BASDAI-stiffness duration4.7±2.76.1±2.8<0.05TJC1.1±2.74.4±6.7<0.01PtGA59.9±22.470.4±18.7<0.05PhyGA39.9±19.750±20.2<0.056-monthASDAS1.6±0.92.8±1.1<0.001BASDAI3.3±2.15.4±2<0.001CRP (mg/L)1.7±2.75.9±7.9<0.01Figure 1.Reasons for b/tsDMARD discontinuation in D2T-axSpA.Disclosure of InterestsManuel Juárez: None declared, Diego Benavent Speakers bureau: Janssen, Roche, Galapagos, Grant/research support from: Novartis, Abbvie, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie and Novartis, Marta Novella-Navarro Speakers bureau: Galapagos, UCB, Lilly and Janssen, Grant/research support from: UCB, Lilly and Janssen, Diana Peiteado: None declared, Alejandro Villalba: None declared, Irene Monjo Speakers bureau: Roche, Novartis, UCB, Gedeon Richter, Consultant of: Roche, Laura Nuño: None declared, Alejandro Balsa Speakers bureau: Pfizer, Abbvie, Lilly, Galapagos, BMS, Sandoz, Nordic Pharma, Gebro, Roche, Sanofi, UCB, Consultant of: Pfizer, Abbvie, Lilly, Galapagos, BMS, Nordic Pharma, Sanofi, UCB, Grant/research support from: Pfizer, Abbvie, BMS, Nordic Pharma, Gebro, Roche, UCB, Chamaida Plasencia Speakers bureau: Pfizer, Abbvie, Lilly, Sandoz, Sanofi, Biogen, Roche, Novartis, Grant/research support from: Pfizer and Abbvie.

BackgroundObesity has been associated with the response to biologic disease modifying anti-rheumatic drugs (bDMARDs). Obese patients have lower response to anti-TNF drugs than to other cytokine-targeted drugs, such as anti-IL6[1]. IL6 receptor inhibition is effective in the treatment of rheumatoid arthritis (RA), and there are two ways of administration: intravenous (IV) weight-adjusted tocilizumab and subcutaneous (SC) fixed-dose tocilizumab or sarilumab. However, evidence regarding the influence of body mass index (BMI) and these different routes of administration is still scarce.ObjectivesTo analyze the role of BMI in the clinical response to antiIL6 therapy in its different routes of administration in patients with RA. To perform an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels and their potential changes according to treatment.MethodsThis study involved 65 patients with RA starting IV tocilizumab at 8mg/kg every 4 weeks or SC antiIL6: tocilizumab 162mg/week or sarilumab 200mg/14days. Demographic and clinical characteristics before antiIL6 initiation (age, sex, smoking habit, age at diagnosis, concomitant and previous treatments and BMI) were collected. Laboratory parameters such as rheumatoid factor and anti-citrullinated peptide antibody were also assessed. Adipokine serum levels (leptin and adiponectin) were measured at baseline and after 6 months (6M) of treatment. Clinical response to treatment was assessed by Clinical Disease Activity Index (CDAI) 6M after initiation of the bDMARD. Differences between variables were assessed using the X2 test and Mann-Whitney test. Correlations between BMI, adipokines and other quantitative variables were assessed using the Pearson or Spearman coefficients. P-values <0.05 were considered statistically significant.ResultsForty seven patients started IV antiIL6 (72.3%) and 18 SC (27.7%). Thirty six (55.4%) achieved low disease activity (LDA)/remission by CDAI: 24 patients from the IV group (51.4%) and 12 (66.7%) from the SC group without significant differences (p=0.19). No differences between BMI or serum adipokine levels were associated with the achievement of LDA/remission when patients were stratified according to the route of antiIL6 administration.Leptin levels in both groups (SC and IV) were very similar at baseline and 6M and regarding changes on adipokine profile between baseline and 6M, we observed a decrease in leptin and an increase in adiponectin levels both in SC and IV (Table 1).Serum adipokine levels (ng/mL)Route of administrationbaseline6 monthspivLeptin18.6 (10.4-30.9)16.9 (7.2-29.2)0.22Adiponectin18310(13250-33890)20610 (12690-33650)0.39scLeptin17.9 (10.1-27.4)16.3 (7.6-30.7)0.22Adiponectin28750 (20570-4394)33350 (24157-49862)0.35BMI showed a significant positive correlation with leptin, overall and stratifying by route of administration, both at baseline and 6M. Adiponectin did not show a significant correlation with BMI.Figure 1.ConclusionObesity and serum adipokines did not show association with the achievement of LDA/remission in patients treated with antiIL6 regardless the route of administration. Furthermore, IV and SC treatments could be used both in obese and normal-weight RA patients expecting the same efficacy.Reference[1]Novella-Navarro et al. Obesity and response to biological therapy in rheumatoid arthritis: the role of body mass index and adipose tissue cytokines. Clin Exp Rheumatol. 2022 Sep;40(9):1726-1732.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundSubclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) is found in the 22.8% of patients on ultrasound examinations. The outcome and the optimal management of subclinical giant cell arteritis (GCA) in patients with polymyalgia rheumatica (PMR) have not been defined yet.ObjectivesThe aim of this study was to investigate the short-term outcome of PMR patients with concurrent subclinical GCA that were included in our multicenter project on the prevalence, characteristics and outcome of subclinical GCA (diagnosed by vascular ultrasound) in PMR [1].MethodsWe analyzed follow up data at 3, 6, 12 and 18 months of consecutive PMR patients from 7 European rheumatology centers. All patients fulfilled 2012 EULAR/ACR Provisional Classification Criteria for Polymyalgia Rheumatica and they had not symptom of clinical GCA. Patients were stratified into two groups: pure PMR and PMR with subclinical GCA, and the outcome between these two groups were compared. A relapse was defined as clinical and/or laboratory worsening of the disease after the initial remission and minor and major relapse EULAR definition was used [2].ResultsWe included 116 PMR patients (47 with concurrent subclinical GCA and 69 with pure PMR) followed for a median (IQR) of 21 (17; 23) months. We observed relapses in 35/116 patients (30.2%), 27/47 (57.4%) in PMR with subclinical GCA and 8/69 (11.6%) in pure PMR group (p<0.001). All relapses in the pure PMR group were minor relapses, whereas we observed 2 major relapses in the subclinical GCA group. The dose of corticosteroids used at the baseline visit was significantly higher in the GCA subclinical group, but tapering of steroids occurred faster than recommended by clinical guidelines [2]. Prednisone dose was significantly higher in patients with PMR and subclinical GCA than in patients with pure PMR both at baseline and at month 6 (Table 1). In patients with PMR with subclinical GCA mean starting dose of prednisone was 32.2±16.1 mg in those who relapsed and 36.2±12.8 in those who maintained remission (p=0.166); at 3 months, it was 13.2±7.1 and 18.2±7.9, respectively (p<0.05). Three patients in the PMR with subclinical GCA group received biological therapy at diagnosis; one of them had a minor relapse.Table 1.Patients characteristicsPure PMR(n=69)Subclinical GCA/PMR(n=47)pAge years (mean ± SD)71.2±8.074.8±7.60.079Sex (females %)59%52%0.526Relapses n (%)8/69 (11.6%)27/47 (57.4%)0.001Minor Relapses n (%)8/69 (11.6%)25/47 (53.2%)0.001Major Relapses n (%)02/47 (4.2%)Steroids basal (mean ± SD))18.3±9.134±14.80.001Steroids month 3 (mean ± SD)9.9±5.114.6±8.30.001Steroids month 6 (mean ± SD)5.6±2.18.8±6.80.037Steroids month 12 (mean ± SD)1.7±2.18.0±14.20.062Steroids month 18 (mean ± SD)1.1±1.83.6±5.60.09Steroids = mg prednisone; SD = standard deviation; n= number of patientsConclusionPMR patients with subclinical GCA had a significantly higher number of relapses during the follow-up than pure PMR group. These results suggest that subclinical GCA in PMR should be treated in the same manner as clinically overt GCA.References[1]De Miguel et al. Prevalence of subclinical giant cell arteritis in patients with polymyalgia rheumatica. Ann Rheum Dis 2022; volume 81, supplement 1, page 122.[2]Hellmich B et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020 Jan;79:19-30.AcknowledgementsWe would like to thank to the GCA/PMR study group for her contributions to the development of collaborative studies.Disclosure of InterestsNone Declared.

BackgroundUltrasound (US) can detect signs of large vessel (LV) involvement at axillary, subclavian and carotid arteries of giant cell arteritis (GCA) patients, but has limited access to the thoracic aorta. Although aortic involvement is not routinely evaluated in all patients with GCA, it may cause a life-threatening situation as result of serious complications such as aneurysms or dissection.ObjectivesOur aim is to determine the added value of performing FDG-PET/CT to detect aortitis in patients with US proven GCA and to identify factors associated with aortic involvement.MethodsRetrospective observational study of patients referred to the US fast track clinics of two academic centres over a 4-years period. Only patients with US proven GCA were included for analysis. Baseline US of cranial and extracranial arteries (carotid, subclavian and axillary) was performed in all patients at diagnosis within 24-48 hours. FDG-PET/CT was performed according to clinician criteria and images were assessed by nuclear medicine physicians. An FDG artery uptake at the thoracic or abdominal aorta higher than liver uptake was defined as aortitis. Between groups comparisons were made in patients with and without aortitis.ResultsSeventy two patients over 186 patients with confirmed GCA by US underwent an FDG-PET/CT (mean age 77 years, 52.8% females). A total of 48 (66.7%) had LV-GCA based on imaging findings, with 29 (40.3%) presenting positive FDG-PET/CT for LV-GCA and 24 (33.3%) presenting artery uptake throughout the aorta suggestive of aortic involvement (Table 1). Only 6 (20.7%) patients had negative US findings of LV-GCA but positive FDG-PET/CT. Among patients with aortitis according to FDG-PET/CT, only 2 (8.3%) had negative US findings of LV-GCA. In contrast, 19 (45.2%) patients with US findings of LV-GCA had negative FDG-PET/CT. 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 level of platelets (413.4 vs 311.1, p=0014). None of the patients with aortitis referred visual symptoms (0% vs 31.2%, p=0.001) and they presented US signs of LV-GCA more frequently (91.7% vs 41.7%, p<0.001) versus patients without aortic involvement.ConclusionFDG-PET/CT can detect aortic involvement in 1 out of every 3 patients with US proven GCA. However, most of these patients show US findings of LV-GCA. In contrast, half of patients with US proven LV-GCA may have negative FDG-PET/CT. Younger and female GCA patients, with thrombocytosis, absence of visual manifestations and US pattern of LV-GCA may present more frequently aortitis by FDG-PET/CT.Table 1.Clinical and imaging findings of patients included with and without aortic involvement.Total n=72Patients with aortic involvement in FDG-PET/CT n=24 (33.3%)Patients without aortic involvement in FDG-PET/CT n=48 (66.7%)pDemographicsAge, mean (SD)77 (9.1)68.9 (8.1)81 (6.5)<0.001Female, n (%)38 (52.8%)19 (79.2%)19 (39.6%)0.002Clinical variablesHeadache, n (%)49 (68.1%)14 (58.3%)35 (72.9%)0.211Jaw claudication, n (%)16 (22.2%)4 (16.7%)12 (25%)0.423Visual symptoms, n (%)15 (20.8%)0 (0%)15 (31.2%)0.001Ocular ischaemia, n (%)6 (8.3%)0 (0%)6 (12.5%)0.07Constitutional symptoms, n (%)42 (58.3%)17 (70.8%)25 (52.1%)0.128Fever, n (%)19 (26.4%)9 (37.5%)10 (20.8%)0.130Morning stiffness in shoulders/neck, n (%)38 (52.8%)10 (41.7%)28 (58.3%)0.182Laboratory findingsCRP (mg/L), mean (SD)85.8 (79.6)101.8 (77.8)77.8 (80.4)0.230ESR (mm/h), mean (SD)68.6 (33.6)69.7 (31.8)68 (34.7)0.839Haemoglobin (g/dL), mean (SD)11.9 (1.6)11.5 (1.5)12.1 (1.7)0.139Platelets 109/L, mean (SD)345.7 (152.1)413.4 (169.7)311.11 (131.1)0.014HistologyTemporal artery biopsy positive n=22, n (%)9 (40.9%)2 (28.6%)7 (46.7%)0.421ImagingPositive cranial ACG US, n (%)50 (69.4%)10 (41.7%)40 (83.3%)<0.001Positive large vessel-GCA US, n (%)42 (58.3%)22 (91.7%)20 (41.7%)<0.001Negative large vessel-GCA US, n (%)30 (41.7%)2 (8.3%)28 (58.3%)<0.001Isolated positive large vessel-ACG US, n (%)22 (30.6%)14 (58.3%)8 (16.7%)<0.001REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.