Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age ± standard deviation 51 ± 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 ± 0.25 vs. 0.9 ± 0.16; p = 0.0001), CAS (4.64 ± 1.5 vs. 1.05 ± 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 ± 4.1 vs. 16.73 ± 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 ± 2.1 months, low disease activity (CAS ≤ 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or inefficacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.

Background/purpose The manifestations of uveitis are well established in axial spondyloarthritis (ax-SpA), but not in psoriatic arthritis (PsA). We aimed to assess, in a large unselected series of PsA: (A) the frequency and clinical features of uveitis; (B) its association with PsA activity, the impact of disease and functional disability, and (C) its relationship with the biological treatment. In addition, a literature review was performed. Methods Retrospective longitudinal study of PsA patients from a single referral hospital. PsA was classified according to the CASPAR criteria, and uveitis was diagnosed by experienced ophthalmologists. Results We studied 406 patients with PsA (46.3±12.3 years). Uveitis was observed in 20 (4.9%). Uveitis was acute in all cases, anterior (80%), unilateral (80%) and recurrent (50%). Patients with uveitis had a higher prevalence of HLA-B27 (45% vs 7.5%, p<0.0001), sacroiliitis on MRI (25% vs 8.3% p=0.027), ocular surface pathology (10% vs 0.8%, p=0.021), and median PsA impact of Disease Score (5.9 (2.1–6.8) vs 1.25 (0.0–3.0), p=0.001) and Bath Ankylosing Spondylitis Functional Index (4 (1.6–5) vs 1.0 (0.0–3.5), p=0.01) than patients without uveitis. The exposure adjusted incidence rate (episodes/100 patients-year) of uveitis before versus after biological treatment decreased with anti-TNFα monoclonal antibodies (56.3 vs 9.4) and increased with etanercept (ETN) (6.03 vs 24.2) and secukinumab (SECU) (0 vs 50) (including only one patient treated in the last two cases). Conclusion The prevalence of uveitis in patients with PsA was about 5%. The pattern was similar to that observed in ax-SpA. Uveitis was associated with a worse quality of life and greater functional disability. The uveitis exposure adjusted incidence rate decreased with anti-TNFα monoclonal antibodies and increased with ETN and SECU.

Background: Janus kinase inhibitors (JAKi) are approved for the treatment of rheumatoid arthritis (RA), aiming to achieve clinical remission. Composite scores such as Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) are influenced by subjective factors, and JAKi may impact these dimensions beyond inflammation. Ultrasound provides a sensitive and objective assessment of synovial activity. Objective: To evaluate clinical and ultrasound-defined remission in RA patients treated with JAKi under routine care. Methods: This cross-sectional study included all consecutive patients treated with baricitinib, filgotinib, tofacitinib, or upadacitinib between 1 November 2022 and 30 April 2023. Clinical remission was defined as DAS28-CRP and ultrasound remission as absence of power Doppler (PD) signal across a standardized 32-joint evaluation. Results: We include 78 patients with established RA; 87.2% were female, with mean age of 59.5 ± 10.8 years and disease duration of 10.6 ± 8.0 years. Most were seropositive for RF and/or ACPA (74.4%), and comorbidities were highly prevalent (93.6%). Clinical remission was observed in 42.3% and ultrasound remission in 56.4%, with no statistically significant differences between JAKi groups. Among 50 patients meeting remission by either definition, 30 (60%) fulfilled both criteria, 11 (22%) had ultrasound remission only, and 9 (18%) met clinical remission without sonographic confirmation. Discordant cases were often associated with osteoarthritis, fibromyalgia, mood disorders, and elevated inflammatory markers. Conclusions: JAKi were effective in achieving remission in many RA patients. Ultrasound revealed residual synovitis despite clinial remission and, conversely, silent remission in cases not meeting DAS28-CRP criterion, reinforcing its value for accurate monitoring and personalized therapeutic decisions. No meaningful clinical or ultrasonographic differences were observed between the various JAK inhibitors, indicating comparable perfomance across agents in routine practice.

Background: Uveitis is the most frequent extraarticular manifestation of axial Spondyloarthritis (axSpA). Effects of Biological Therapy (BT) on uveitis associated to axSpA are contradictory (1-3).Objectives: To assess in uveitis associated to axSpA a) frequency and features of uveitis, and b) efficacy and relation of BT in a single-center university study.Methods: Observational study from a cohort of 301 consecutive unselected patients with axSpA classified according to the Assessment of SpondyloArthritis International Society criteria. Episodes of uveitis were analyzed before and after BT initiation. Likewise, uveitis incidence rate (episodes/100 patients/year) at baseline and after first BT was calculated.Results: Uveitis was observed in 44 (25 men/19 women) out of 301 (14.6%) patients. Mean age was 45.6 ± 10.3 years. Demographic and clinical features in patients who developed uveitis and those that did not are summarized in Table 1. After 18.6 ± 10.4 years of follow-up, 44 (14.6%) patients suffered from at least one episode of uveitis. Uveitis was anterior and acute in all cases and unilateral in 37 (84.1%) patients. Mean anterior chamber cells was 1.7 ± 1.2 cells.Per episode of uveitis, 20 patients received BT with: secukinumab (SECU) (n=7, 35%), adalimumab (n=6, 30%), golimumab (n=3, 15%), infliximab (n=2, 10%), certolizumab (n=1, 5%), and etarnecept (ETN) (n=1, 5%). Before the initiation of BT, patients treated with SECU developed 29.7 episodes/100 patients/year while those treated with monoclonal anti-TNFα 16.3 episodes/100 patients/year and patients with ETN 5.8 episodes/100 patients/year. After 5.9 ± 3.7 years of follow-up, patients treated with SECU developed 16.1 episodes/100 patients/year while those treated with monoclonal anti-TNFα 7.6 episodes/100 patients/year and patients with ETN 0 episodes/100 patients/year (Figure 1). No serious adverse effects were observed.Conclusion: Uveitis was observed in 14.6% of axSpA. Most of them were HLA-B27 positive. Acute, anterior and unilateral was the most frequent pattern of uveitis in axSpA. There was a similar decrease in incidence rate between patients treated with SECU and those treated with monoclonal anti-TNFα.References: [1]Deodhar AA, et al. ACR Open Rheumatol. 2020; 2:294-299.[2]Roche D, et al [abstract]. Arthritis Rheumatol 2019; 71 (suppl 10).[3]Lindström U, et al Annals of the Rheumatic Diseases 2020;79:9-10. Table 1. Main general features and differences between patients with and without uveitis. Overalln= 301 Uveitisn= 44 Non uveitisn= 257 p Age, years (mean±SD) 44.9 ± 11.8 45.6 ± 10.3 44.8 ± 12.1 0.47 Gender, n (m/w) (%) 179/122 (59.5/40.5) 25/19 (56.8/43.2) 154/103 (59.9/40.1) 0.71 HLAB27 positive,n (%) 190 (63.1) 37 (84.1) 153 (60.0) 0.00 Follow-up of axSpA, year (mean±SD) 13.5 ± 11.2 18.6 ± 10.5 12.6 ± 11.1 0.33 Family history, n (%) 84 (27.9) 15 (34.1) 69 (27.2) 0.35 r-axSpA, n (%) 217 (72.1) 36 (81.8) 181 (70.4) 0.12 nr-axSpA, n (%) 84 (27.9) 8 (18.2) 76 (29.6) 0.12 Enthesitis, n (%) 108 (35.9) 14 (31.8) 94 (36.6) 0.54 Peripheral arthritis, n (%) 96 (31.9) 12 (27.3) 84 (32.7) 0.47 Psoriasis, n (%) 35 (11.6) 6 (13.6) 29 (11.3) 0.65 Inflammatory bowel disease, n (%) 22 (7.3) 2 (4.5) 20 (7.8) 0.45 Hip involvement, n (%) 20 (6.6) 3 (6.8) 17 (6.6) 0.96 Dactylitis, n (%) 17 (5.7) 3 (6.8) 14 (5.4) 0.72 Cardiovascular event, n (%) 7 (2.3) 1 (2.3) 6 (2.3) 0.98 Figure 1. Uveitis incidence rate before and after biological therapy. Disclosure of Interests: Alba Herrero-Morant: None declared, Iñigo González-Mazón: None declared, Vanesa Calvo-Río Speakers bureau: Abbott, Lilly, Celgene, Grünenthal, UCB Pharma, Grant/research support from: MSD and Roche, Javier Rueda-Gotor: None declared, Miguel Á. González-Gay Speakers bureau: AbbVie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: AbbVie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, Sanofi, Lilly and MSD, Grant/research support from: AbbVie, MSD and Roche

Background/Objectives: Leukocyte telomere length (TL) is a marker of biological aging associated with cardiovascular disease, chronic kidney disease, and malignancy in the general population. Its long-term prognostic significance in systemic lupus erythematosus (SLE) remains unclear. We aimed to evaluate the association between baseline TL and long-term clinical outcomes in patients with SLE. Methods: Prospective cohort study including 97 Caucasian women with SLE. Relative TL was measured in whole blood using quantitative polymerase chain reaction (qPCR) at baseline. A control group of 50 healthy Caucasian women from the same geographical region was included for comparison. Patients were followed for a mean of 9.7 ± 2.8 years. Outcomes included thrombotic cardiovascular events, damage accrual, incident malignancy, and chronic kidney disease. Associations were assessed using multivariable regression models adjusted for potential confounders. Results: Mean age was 51.6 ± 13.8 years and mean relative TL was 4.3 ± 1.0. Relative TL was inversely associated with age (β = −0.20, p = 0.048) and was shorter in patients with hematological manifestations (p = 0.038). No differences in relative TL were observed between SLE patients and controls. Relative TL was not associated with disease activity, cumulative damage, cardiovascular risk factors, vitamin D levels, or subclinical atherosclerosis. During follow-up, 13.4% of patients experienced cardiovascular events, 10.3% developed malignancy, and 11.3% developed chronic kidney disease. Relative TL was initially associated with long-term damage accrual, glomerular filtration rate and cardiovascular events; however, after adjustment for age, only the association with glomerular filtration rate remained at the limit of statistical significance (p = 0.05). Conclusions: In this prospective cohort, relative TL was primarily associated with aging, hematological manifestations, and glomerular filtration rate, but not with disease activity or most long-term clinical outcomes. These findings suggest that TL reflects biological aging rather than disease-specific processes and has limited utility as a prognostic biomarker in SLE.