BackgroundAcute anterior uveitis (AAU) is the most common extra-articular manifestation in patients with axial spondyloarthritis (axSpA). C-VIEW investigates the impact of the Fc-free TNF inhibitor certolizumab pegol (CZP) on AAU flares in patients with active axSpA at high risk of recurrent AAU.MethodsC-VIEW (NCT03020992) is a 96-week ongoing, multicentre, open-label, phase 4 study. Included patients had an axSpA diagnosis, a history of recurrent AAU (≥2 AAU flares, ≥1 flare in the year prior to study entry), HLA-B27 positivity, active disease, and failure of ≥2 non-steroidal anti-inflammatory drugs. Patients received CZP 400 mg at Weeks 0/2/4, then 200 mg every 2 weeks up to 96 weeks. This 48-week pre-planned interim analysis compares AAU flare incidence in the 48 weeks before and after initiation of CZP treatment, using Poisson regression to account for possible within-patient correlations.ResultsIn total, 89 patients were included (male: 63%; radiographic/non-radiographic axSpA: 85%/15%; mean axSpA disease duration: 8.6 years). During 48 weeks’ CZP treatment, 13 (15%) patients experienced 15 AAU flares, representing an 87% reduction in AAU incidence rate (146.6 per 100 patient-years (PY) in the 48 weeks pre-baseline to 18.7 per 100 PY during CZP treatment). Poisson regression analysis showed that the incidence rate of AAU per patient reduced from 1.5 to 0.2 (p<0.001). No new safety signals were identified.ConclusionsThere was a significant reduction in the AAU flare rate during 48 weeks of CZP treatment, indicating that CZP is a suitable treatment option for patients with active axSpA and a history of recurrent AAU.

Background:Acute anterior uveitis (AAU), inflammation of the anterior uveal tract, is reported in up to 40% of patients (pts) with axial spondyloarthritis (axSpA).1AAU is associated with significant clinical burden; symptoms include blurred vision, photophobia and pain.2Previous studies have shown that TNF inhibitors (TNFi) can reduce AAU flare incidence in pts with radiographic axSpA,3-5but few have focused on pts across the full axSpA spectrum.Objectives:To analyse the impact of certolizumab pegol (CZP) treatment on AAU in pts with active radiographic and non-radiographic axSpA and a recent history of AAU.Methods:C-VIEW (NCT03020992) is an ongoing multicentre, open-label, phase 4 study. Pts had active axSpA according to the ASAS classification, a history of recurrent AAU (≥2 AAU flares in total and ≥1 AAU flare in the year prior to study entry), were HLA-B27 positive, and were eligible for TNFi treatment (previous failure of ≥2 NSAIDs, biologic naïve or had failed ≤1 TNFi). Pts received CZP 400 mg at Weeks (Wks) 0/2/4, then 200 mg every two wks (Q2W) to Wk 96. The primary variable was incidence of AAU flares compared to historic rates. A pre-specified interim analysis compared AAU incidence in the 48 wks prior to CZP treatment with the 48 wks of treatment, using Poisson regression adjusted for possible within-pt correlations, with period (pre- and post-baseline) and axSpA disease duration as covariates. Incidence rates (IR) were calculated based on the number of cases/pts at risk over 48 wks. Observed data are reported.Results:Of 115 enrolled pts, 89 initiated CZP treatment; 85 completed Wk 48. Baseline characteristics are shown in the Table. The 48-wk interim analysis revealed significantly fewer AAU flares/pt during CZP treatment vs before treatment (Figure; Poisson-adjusted IR: 0.2 vs 1.5, p<0.001). The number of pts experiencing 1 and ≥2 AAU flares (64.0% and 31.5% respectively) substantially reduced during CZP treatment (12.4% and 2.2%). After 48 wks CZP treatment, disease activity improved substantially (mean ± SD Ankylosing Spondylitis Disease Activity Score [ASDAS]: 2.0 ± 0.9; Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]: 3.3 ± 2.1), with 31.4% pts achieving ASAS partial remission and 29.1% ASDAS major improvement. No new safety signals were identified.Table.Baseline characteristicsCZP 200 mg Q2W (N=89)Age (years), mean ± SD46.5 ± 11.2Male, n (%)56 (62.9)Racial group, n (%) Caucasian87 (97.8) Other2 (2.2)Diagnosis, n (%) Radiographic axSpA76 (85.4) Non-radiographic axSpA13 (14.6)Duration of axSpA (years), mean ± SD8.6 ± 8.4Time since onset of first uveitis flare (years), mean ± SD9.9 ± 9.0ASDAS, mean ± SD3.5 ± 0.9BASDAI, mean ± SD6.5 ± 1.5Conclusion:In this open-label study, AAU flare rate significantly reduced in axSpA pts with a history of recurrent AAU during the first 48 wks of CZP. Pts also experienced substantial improvements in axSpA disease activity.References:[1]Martin TM. Curr Opin Rheumatol 2002;14:337–41[2]Bacchiega ABS. Rheumatology (Oxford) 2017;56:2060–7[3]van der Heijde D. Rheumatology (Oxford) 2017;56:1498–509[4]van Bentum RE. J Rheumatol 2019;46:153–9[5]van Denderen JC. J Rheumatol 2014;41:1843–8Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Rianne van Bentum: None declared, Frank Verbraak Grant/research support from: Bayer, Novartis, IDxDR, UCB Pharma, Consultant of: Bayer, Novartis, IDxDR, UCB Pharma, Thomas Rath Grant/research support from: AbbVie, Bristol-Myers Squibb, Chugai, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, James Rosenbaum Consultant of: AbbVie, Corvus, Eyevensys, Gilead, Novartis, Janssen, Roche, UCB Pharma; royalties from UpToDate, Maria Misterska-Skora: None declared, Bengt Hoepken Employee of: UCB Pharma, Oscar Irvin-Sellers Employee of: UCB Pharma, Brenda VanLunen Employee of: UCB Pharma, Lars Bauer Employee of: UCB Pharma, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma

BackgroundOne third of the axial spondyloarthritis (axSpA) patients suffers from acute anterior uveitis (AAU). Correspondently, AAU can be the first sign of axSpA and previous studies described undetected axSpA in up to 40% of the patients with noninfectious AAU.ObjectivesTo study whether referral of all patients with AAU and chronic back pain results in a high prevalence of newly diagnosed axSpA patients.Table 1Patient characteristics at referral.Overall (N=50)Definite AxSpA (N=13)Suspicion of early axSpA (N=21)No suspicion of axSpA (N=16)Age 42 (±13)44 (±15)38 (±9)45 (±15)Gender, men26 (52)10 (77)11 (52)5 (31)Back pain duration, years 15 (5-27)14 (5-27)9 (4-24)21 (15-32)Inflammatory back pain21 (42)9 (70) 9 (43)3 (19)>1 anterior uveitis26 (52)9 (69)12 (57)5 (31)HLA-B27 positive27 (54)11 (85)12 (57)4 (25)SpA features (ASAS)3 (±1)4 (±1) 3 (±1)2 (±1)SI joint abnormality16 (32)9 (69)6 (29)1 (6)Sacroiliitis, mNY criteria9 (18)7 (54)2 (10)0 (0)BASMI2.4 (±2.4)4.2 (±4.0)1.6 (±0.7)2.0 (±1.3)BASDAI3 (2-5)2 (2-4)3 (2-5)3 (2-5)ASDAS-CRP ≥2.121 (42)6 (46)10 (48)5 (31)Legend: Numbers are depicted as mean (±SD), median (Q1-Q3) or number of patients (%).MethodsA prospective ongoing observational study was started in April 2017, including all patients with noninfectious AAU and a history of back pain (≥3 months, started < age of 45 years), referred from six Ophthalmology clinics to the Rheumatology Outpatient Clinic of the VU medical center. Patients with a known systemic disease associated with AAU were excluded. Patient characteristics, laboratory (HLA-B27, C-reactive protein) and patient reported parameters (e.g. BASDAI, ASDAS) were collected. X-rays were evaluated according to the modified New York (mNY) criteria for sacroiliitis. The clinical axSpA diagnosis was made by the rheumatologist. Patients were either diagnosed with ‘definite SpA’, ‘suspicion of SpA’ or ‘no suspicion of SpA’, based on the clinical assessment. Patients with ‘definite SpA’ were classified into radiographic or non-radiographic axSpA according to the ASAS criteria. Patients were treated according to standard care guidelines.ResultsBetween April 2017 and October 2018, 65 patients were referred to the Rheumatology clinic, of whom 50 (mean age 42 years; 48% female; median back pain duration 15 years) met all inclusion criteria. AxSpA was diagnosed in 13 patients (26%), of whom seven fulfilled the criteria for radiographic and six for non-radiographic axSpA (table 1). Another 21 patients (42%) were considered clinically suspicious for early axSpA, of whom four had SI joint abnormalities and two even fulfilled the mNY criteria for sacroiliitis. Forty-two% of all patients had a high disease activity score (ASDAS≥2.1). Patients diagnosed with axSpA were significantly more often male and HLA-B27 positive, had more SpA features and a higher BASMI score. In 25 patients treatment was started, mostly with nonsteroidal anti-inflammatory drugs. Two patients received a tumor necrosis factor inhibitor shortly after diagnosis.ConclusionIn this study, 26% of the patient...

Background:Chronic systemic inflammation in patients with ankylosing spondylitis (AS) contributes to the development of cardiovascular disease (CVD). Microvascular changes are thought to precede clinically overt CVD and its early recognition could improve timely treatment. The microvasculature of the retina and fingertips are easily accessible for non-invasive visualization. Furthermore, previous studies have shown an association between CVD and respectively retinal morphology and digital microvascular function (fingertips), in patients without rheumatic diseases. The retinal and digital vasculature could provide an unique opportunity to recognize early signs of CVD in aS patients.Objectives:To investigate whether retinal vascular parameters and digital microvascular function in aS patients are associated with the 10 year CVD risk.Methods:Cross-sectional study in aS patients (diagnosis according to modified New York criteria) between 50-75 years without a history of diabetes mellitus or cerebrovascular disease. Consecutive patients were recruited consecutively from the Rheumatology outpatient clinic of the amsterdam UMC, location VUmc and Reade. Patient characteristics, CVD (risk factors), disease duration/activity (ASDAS), C-reactive protein and lipid profile were assessed. The digital microvascular function (the reactive hyperemia index, RHI) was tested through endo Peripheral arterial Tone measurement at the finger tips (EndoPAT). Retinal vascular parameters were assessed through fundus photography, and identified with Singapore I Vessel assessment (SIVA) software: central retinal artery and vein equivalent (CRAE, CRVE), arteriovenous ratio (AVR), curvature tortuosity arterioles and venules (cTORTa, cTORTv), fractal dimension of arteries and venules (FrDiA, FrDiV). SIVA parameters were reported as continuous values. The Framingham risk score (FRS) was calculated and classified based on the 10 years CVD risk (low risk <10%, intermediate risk 10-20%, high risk >20%). Linear regression analyses were used to determine the association between the FRS categories and retinal parameters or digital microvascular function (RHI), correcting for age and disease duration.Results:Fifty-three aS patients were included (age 60±6 years, 55% female, 74% HLA-B27 positive, disease duration 35 years ±13, aSDAS 2.3±1.0). Fifty-five% was currently treated with NSAIDs and 47% with a TNF inhibitor. Based on the FRS, 36% had a high risk of CVD in the next 10 years, 42% an intermediate and 12% a low risk. In multivariable analyses, patients with an intermediate and high risk of CVD (FRS) had a significantly lower diameter of the central retinal artery (CRAE; p<0.01 for both risk groups) and arteriovenous ratio (AVR; only for high risk; p=0.03) as compared with patients with a low risk. There was no association between the RHI and the cardiovascular risk.Conclusion:This study suggests an association between the 10 years CVD risk and the morphology of the retinal arterial vessels in older aS patients (≥50 years). This is in accordance with...

Background:Acute anterior uveitis (AAU) is the most common extra-articular manifestation in axial spondyloarthritis (axSpA), affecting up to 40% of patients and causing significant burden.1 Previous studies have shown that tumour necrosis factor inhibitors (TNFi) can reduce the incidence of AAU flares in patients with radiographic axSpA (ankylosing spondylitis),2-4 but few have focused on patients across the full axSpA spectrum.1Objectives:To report 2-year outcomes from the phase 4, open-label C-VIEW study (NCT03020992), which investigated the impact of certolizumab pegol (CZP) treatment on AAU in patients with active axSpA and a recent history of AAU.Methods:C-VIEW prospectively investigated patients with active axSpA who were HLA-B27 positive and had recurrent AAU, with a history of ≥1 AAU flare in the year prior to baseline (additional study criteria and study design are described elsewhere5). The primary efficacy variable was the incidence of AAU flares during 96 weeks of CZP treatment versus the 2-year pre-baseline period. AAU incidence was evaluated using Poisson regression adjusted for duration of time in each period, with period (pre- and post-baseline) and axSpA disease duration as covariates. Secondary efficacy variables were Assessment of SpondyloArthritis international Society 20%/40% (ASAS20/40) response rates, as well as mean Ankylosing Spondylitis Disease Activity Score (ASDAS) and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) to Week 96.Results:Of 115 enrolled patients, 89 initiated CZP treatment; 83 completed Week 96. The primary analysis revealed an 82% reduction in the incidence of AAU flares during CZP treatment compared with pre-baseline (Figure 1A; rate ratio [95% CI]: 0.18 [0.12, 0.28], p<0.001). The percentage of patients experiencing ≥1 and ≥2 AAU flares reduced from 100% and 59.6% pre-baseline to 20.2% and 11.2% during treatment (Figure 1B). There were also improvements in axSpA disease activity (Table 1): by Week 96, 75.6% and 58.5% of patients had achieved ASAS20 and ASAS40 responses, respectively. ASDAS and BASDAI also improved substantially over the 96-week treatment period. No new safety signal was identified, compared to previous reports.5Conclusion:These data support the use of CZP for the treatment of patients with axSpA and a history of recurrent AAU. During 96 weeks’ CZP treatment, there was a significant reduction of 82% in the AAU flare rate compared to pre-baseline. There were also substantial improvements in patients’ axSpA disease activity.References:[1]Martin TM. Curr Opin Rheumatol 2002;14:337–41.[2]van der Heijde D. Rheumatology (Oxford) 2017;56:1498–509.[3]van Bentum RE. J Rheumatol 2019;46:153–9.[4]van Denderen JC. J Rheumatol 2014;41:1843–8.[5]van der Horst-Bruinsma I. RMD Open 2020;6:e001161.Table 1.Changes in axSpA disease activity to Week 96Disease activity measureWeek 0(n=89)Week 48(n=86)Week 96(n=82)ASAS responder rates, n (%)ASAS20N/A65 (75.6)62 (75.6)ASAS40N/A46 (53.5)48 (58.5)ASDAS, mean (SD)3.5 (1.0)2.0 (0.9)1.9 (1.0)BASDAI, mean (SD)6.5 (1.5)3.3 (2.1)3.0 (2.1)Observed data are shown. Patients received CZP 400 mg at Weeks 0/2/4, then 200 mg Q2W through 96 weeks. ASAS20/40: Assessment of SpondyloArthritis international Society 20%/40%; ASDAS: Ankylosing Spondylitis Disease Activity Score; axSpA: axial spondyloarthritis; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; CZP: certolizumab pegol; Q2W: every 2 weeks; SD: standard deviation.Acknowledgements:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Irene van der Horst-Bruinsma Speakers bureau: AbbVie, BMS, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, UCB Pharma, Grant/research support from: AbbVie, MSD, Pfizer, Rianne van Bentum: None declared, Frank Verbraak Speakers bureau: Bayer, IDxDR, Novartis, UMC, Consultant of: Bayer, Novartis, Grant/research support from: Bayer, Thomas Rath Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Bengt Hoepken Shareholder of: UBC Pharma, Employee of: UCB Pharma, Oscar Irvin-Sellers Shareholder of: UCB Pharma, Employee of: UCB Pharma, Thomas Kumke Shareholder of: UCB Pharma, Employee of: UCB Pharma, Lars Bauer Shareholder of: UCB Pharma, Employee of: UCB Pharma, Martin Rudwaleit Speakers bureau: AbbVie, Eli Lilly, Novartis, UCB Pharma, Consultant of: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, UCB Pharma