Early Axial Spondyloarthritis Research Articles

Head-to-head studies on radiographic progression in axial spondyloarthritis

In this review article four clinical comparative studies in axial spondylarthritis (axSpA) are presented and discussed. SURPASS as the only head-to-head study investigated the effect of adalimumab biosimilar disease-modifying antirheumatic drug (bsDMARD) or secukinumab on radiographic progression over a time period of 2 years. Overall, the radiographic progression of the spine was low and no significant difference between adalimumab bsDMARD or secukinumab was noted. The three other studies were not constructed as direct head-to-head studies but compared the efficacy of non-steroidal antirheumatic drugs (NSARD) with and without simultaneous treatment with biological DMARDs (bDMARD). The CONSUL study showed no statistically significant difference in the delay of radiographic progression of the spine over 2 years in radiographic axSpA (r-axSpA) patients, who underwent either combined treatment with golimumab and celecoxib or treatment with golimumab alone over 2 years. The ESTHER study showed that patients with early axSpA active inflammatory lesions, which were detected by whole-body magnetic resonance imaging (MRI), showed a significantly greater improvement under treatment with etanercept than those treated with sulfasalazine. The INFAST study showed that patients with early active axSpA who received a combined treatment of infliximab and naproxen, achieved a clinical remission twice as frequently as those who only received naproxen. Therefore, for the endpoint of radiological progression no difference could be shown in the inhibition of radiological progression between the mechanisms of action investigated. The comparative data for the endpoint of clinical efficacy showed that patients with bDMARDs showed a clearly better response to treatment than patients with NSAR or conventional synthetic DMARDs (csDMARD).

OA11 Maintained improvement in patient reported outcomes in early axial spondyloarthritis following certolizumab pegol dose reduction

Abstract Background/Aims Certolizumab pegol (CZP), a PEGylated TNFi without an Fc region, has previously shown efficacy and safety in patients with axial spondyloarthritis (axSpA). EULAR guidelines recommend that tapering of a biologic can be considered for patients in sustained remission. The C-OPTIMISE trial (NCT02505542) identified early (<5 years) axSpA patients in sustained remission who may benefit from dose tapering or stopping treatment. Here we report whether a reduced CZP maintenance dose is associated with sustained improvements in patient reported outcomes (PROs) in patients with axSpA at Week (Wk) 96. Methods C-OPTIMISE was a two-part, multicentre, phase 3b study in adult patients. Part A: up to Wk48 (open-label), patients received CZP 200mg Q2W. At Wk48 (Part B), patients who achieved sustained remission at Wk32 or 36 (ASDAS <1.3), were randomised 1:1:1 to double-blind CZP 200 mg Q2W (full maintenance dose), CZP 200 mg Q4W (reduced maintenance dose), or placebo (PBO [drug withdrawal]) for additional 48Wks. We report disease activity and PROs (BASDAI, PtGADA, nocturnal apinal pain, morning stiffness, fatigue, and ASQoL) during Part B (Wks48-96). Flare is defined as ASDAS ≥2.1 at two consecutive visits, or ASDAS >3.5 at any visit. Results At Wk48 (Part A), 43.9% (323/736) of patients achieved sustained remission, of which 313 patients were randomised to Part B (Wks48-96). During Wks48-96, 87/104 (83.7%) patients receiving the full maintenance dose, 83/105 (79.0%) patients receiving the reduced maintenance dose, and 21/104 (20.2%) patients receiving PBO remained flare-free. Patients receiving full maintenance and those on reduced dose have similar disease activity measures (BASDAI; mean [SD], 0.8 [0.8] vs 0.8 [1.0]) at Wk96 (Table). Sustained improvements in PROs were similar for CZP full maintenance dose and CZP reduced maintenance dose, including ASQoL, fatigue and nocturnal spinal pain, while PBO showed increased disease activity (Table). Conclusion In axSpA patients who achieved sustained remission, CZP reduced dosage resulted in sustained improvements in disease activity and PROs similar to those receiving full maintenance dose. This suggests that dose reduction can be a viable strategy without compromising PROs. Disclosure A. Chan: Member of speakers’ bureau; AC has received speaker bureau from Novartis, UCB, Abbvie, Janssen, Amgen. Grants/research support; AC has received grant support for service and educational projects from Novartis and UCB Pharma. Other; AC has received honoraria/advisory boards from Novartis, Abbvie, UCB, Janssen, Amgen, Lilly. J. Wood: Other; JW is an employee of UCB Pharma. L. Burns: Other; LBu is an employee of UCB Pharma. R. Tham: Other; RT is employed by Veramed and a contractor for UCB Pharma. T. Kumke: Other; TK is an employee and shareholder of UCB Pharma. B. Hoepken: Other; BH is an employee and shareholder of UCB Pharma. M. Kim: Other; MK is an employee of UCB Pharma. L. Bauer: Other; LBa is an employee and shareholder of UCB Pharma. K. MacKay: Other; KM received consultancy & speaker meetings for UCB, AbbVie, Novartis, Lilly, AZ, Janssen and Roche. K. Gaffney: Shareholder/stock ownership; KG is a shareholder of Rheumatology Events. Grants/research support; KG has received grants/research support from NASS, Versus Arthritis, AbbVie, Pfizer, UCB Pharma, Norvartis, Eli Lilly, Cellgene, Celltrion, Janssen, Gilead and Biogen. Other; KG has received honoraria/ consultation fees from Novartis, AbbVie, UCB Pharma, Lilly and Pfizer, KG has received speaker’s bureau from Novartis, UCB Pharma, AbbVie and Lilly; meeting expenses from AbbVie, Lilly, Roche, Novartis, Pfizer and UCB Pharma.

Factors Associated With Treatment Pathways in Early Axial Spondyloarthritis: A Multistate Analysis of the 10-Year Follow-Up of the DESIR Cohort.

Current recommendations for the management of patients with axial spondyloarthritis (axSpA) emphasize the need of an individualized strategy in therapeutic decision-making. The study objectives were to describe therapeutic strategies observed in axSpA, and to assess the factors associated with treatment intensification over time. We included patients with axSpA from the French prospective cohort DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes), with a scheduled 10-year follow-up. A multistate model with 4 ordered treatment states (no treatment, nonsteroidal antiinflammatory drugs [NSAIDs], conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], and tumor necrosis factor inhibitors [TNFi]) was defined, with 6 possible transitions. Restricted mean sojourn times in each state were estimated. Then, predictors of those transitions were assessed by multivariable Cox models. A total of 686/708 (96.9%) patients who had > 1 visit were analyzed. At cohort entry, 199 (29%) were untreated, 427 (62.2%) were receiving NSAIDs, 60 (8.7%) csDMARDs, and none were receiving TNFi. Over the follow-up period, patients mostly (46.4% of the time) received NSAIDs, followed by TNFi (24.4% of the time). The presence of sacroiliitis on radiographs, inflammatory bowel disease, and articular index were jointly associated with the transition to NSAIDs. Longer duration in the previous state often decreased the hazard of the transition to csDMARDs or TNFi. Worse disease activity outcomes increased the hazard of most transitions. To our knowledge, this was the first study using a multistate model to easily represent different treatment states, detailing the transitions across them and their associated factors. Different time profiles for the management of patients with axSpA were identified, including in those abstaining from treatment up to a significant proportion of patients treated with csDMARDs.

Early axial spondyloarthritis according to the ASAS consensus definition: characterisation of patients and effectiveness of a first TNF inhibitor in a large observational registry

ObjectiveTo characterise the population fulfilling the Assessment of SpondyloArthritis international Society (ASAS) consensus definition of early axial spondyloarthritis (axSpA) and to determine the effectiveness of a first tumour necrosis factor...

Differences in the course of coxitis in men and women with early axial spondyloarthritis

Introduction. Currently, there is a small number of studies devoted to the differences in the manifestations of axial spondyloarthritis (axSpA) in men and women, and there are no studies assessing the frequency of coxitis in axSpA in patients of different sexes. The purpose of the study is to compare the main manifestations of coxitis in axial spondyloarthritis in men and women. Material and methods. The study was conducted on the Moscow Cohort of Early SpondyloArthritis (CoRSAr), which currently includes 175 patients. Their age at the time of inclusion in the cohort was on average 28.5±5.8 years, the duration of the disease was 24.1±15.4 months. 92.6% of patients were positive for HLA-B27 (human leukocyte antigen B27). All patients were assessed for pain in the hip joints (HIP) using a numerical rating scale (NRS) (0–10), and pelvic radiography, magnetic resonance imaging (MRI) and ultrasound examination of the Hip joint were performed. An increase in the cervical-capsular distance (NCD) of more than 7.0 mm was considered a sign of coxitis according to ultrasound data. When analyzing MRI results, signs of coxitis were considered to be synovitis and/or osteitis of the femoral head or acetabulum. X-ray changes in the hip joint were assessed using the BASRI-hip index (Bath Ankylosing Spondylitis Radiology Hip Index). Results and discussion. Among the 175 patients, there were 97 (55.4%) men and 79 (44.6%) women. At the time of inclusion in the study, women were older than men (p<0.01), while the duration of the disease in men and women was the same and averaged about 2 years. In men, X-ray changes in the hip joint were more common than in women (in 7.2% and 1.3% of cases, respectively; p<0.05). Clinical signs of coxitis were detected in 54 (55.7%) men and 41 (51.9%) women, while the level of pain according to the NRS in women averaged about 2, and in men – about 3 points (p>0.05). According to ultrasound data, coxitis was detected in 15 (18.9%) women and 27 (27.8%) men; NCD averaged 6.2 mm in men and 5.9 mm in women (p>0.05). In men, signs of damage to the hip joint according to MRI were more common than in women (in 27.8% and 15.1% of cases, respectively; p<0.05). The level of C-reactive protein (CRP) in men was also higher than in women (on average 12.8 and 4.3 mg/l, respectively; p<0.05). Conclusion. Women develop axSpA at a later age than men, and the latter are more likely to have HLA-B27, MRI features of coxitis, and higher levels of CRP.

Looking through the window of opportunity in axial spondyloarthritis?

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine and sacroiliac joints, that can lead to irreversible structural damage. Early detection and timely intervention are crucial for preventing long-term structural damage, improving quality of life, and reducing the burden of the disease. The concept of a window of opportunity suggests that an early intervention in the reversible stage of the disease can lead to improved long-term outcomes. However, it is unclear whether this concept applies in axSpA. Recent advances in axSpA management, including the use of diagnostic techniques such as magnetic resonance imaging as well as the use of advanced therapies, have shown promise in improving outcomes. However, studies investigating the potential window of opportunity in axSpA by assessing the impact of an early treatment on clinical outcomes have yielded inconclusive results. One of the reasons behind this is the lack of a standardized definition of early axSpA. The Assessment of Spondyloarthritis International Society (ASAS)-SPEAR (SPondyloarthritis EARly) project has set the ground for it by working on a consensus definition of early axSpA. Randomized controlled trials specifically focused on the comparison between treating axSpA in the early and late stages of the disease and using the standardised definition of early axSpA are essential to understand better the potential benefits of an early treatment on clinical outcomes. Additionally, it would be relevant to assess the long-term outcomes of early axSpA treatment, especially regarding structural damage, to better grasp the concept of the window of opportunity in axSpA.

Bone marrow edema in the sacroiliac joints is associated with the development of structural lesions at the same anatomical location over time in patients with axial spondyloarthritis

ObjectiveTo assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to investigate the association between BME patterns over time and structural lesions in patients with early axial spondyloarthritis (axSpA). MethodsPatients with axSpA from the DESIR cohort with ≥2 consecutive magnetic resonance imaging (MRI)-SIJ were assessed at baseline, 2 and 5 years. MRI-SIJ images were divided into 8 quadrants. The association between BME and subsequent structural lesions (sclerosis, erosions, fatty lesions, and ankylosis) on MRI in the same quadrant was tested longitudinally. Additionally, patients were grouped according to the pattern of BME evolution across quadrants over time (no BME, sporadic, fluctuating, and persistent). The association between these patterns and 5-year imaging outcomes (eg: ≥5 erosions and/or fatty lesions on MRI-SIJ) was tested. ResultsIn total, 196 patients were included. BME in each quadrant was associated with sclerosis (OR:1.9 (95%CI: 1.1;3.4)), erosions (1.9 (1.5;2.5)) and fatty lesions (1.9 (1.4;2.6)). Ankylosis was uncommon. There was a gradient between increased level of inflammation and subsequent damage: compared to the ‘no BME’ pattern, the sporadic (OR (95% CI): 2.1 (1.0;4.5)), fluctuating (OR:5.6(2.2;14.4)) and persistent (OR:7.5(2.8;19.6)) patterns were associated with higher structural damage on MRI-SIJ at 5-years. ConclusionsIn early axSpA, inflammation on MRI-SIJ leads to damage at the quadrant level. The higher the exposure to inflammation across quadrants in the SIJs over time the higher the likelihood of subsequent structural damage, suggesting a cumulative effect.

Influence of Sex on Early Axial Spondyloarthritis: A Six-Year Longitudinal Analysis From a Large National Cohort.

The objective was to determine sex differences in disease outcomes in recent axial spondyloarthritis (SpA) over time. We analyzed the first 6 years of follow-up of the prospective French multicenter DESIR cohort. Patients analyzed had <3 years of disease, were naive to disease-modifying antirheumatic drugs, and fulfilled the Assessment of SpondyloArthritis international Society classification criteria for axial SpA. Disease activity (Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level), patient global assessment (PtGA), CRP level, and radiographic sacroiliitis were compared between men and women (self-reported sex) by linear and logistic mixed-effects models.Models were created for trajectories of disease activity over 6 years in men and women, using k-means. Of 494 patients analyzed (mean ± SD age 31.9 ± 7.5 years, symptoms duration 20.7 ± 11.7 months), 50.4% were men. Over 6 years of follow-up, both men and women showed clear improvements in ASDAS-CRP, PtGA, and CRP level. Women had higher ASDAS-CRP and PtGA over time compared to men (both P < 0.0001) with overall similar CRP levels (P=0.089), whereas structural damage increased more in men (P < 0.0001). One-third of both men (33%) and women (34%) belonged to persistent high/very high disease activity trajectories, but ASDAS-CRP was globally higher in women in these trajectories. In early axial SpA, clinical outcomes (disease activity and symptoms) were worse in women than men over 6 years of follow-up, whereas CRP was similar and structural damage was more frequent in men. Although similarly distributed, disease activity scores were higher in women in high/very high disease activity trajectories. Sex appears to be an important contextual factor in axial SpA.

Relationship between sex and clinical and imaging features of early axial spondyloarthritis: results from a 48 month follow-up (Italian arm of the SPondyloArthritis Caught Early (SPACE) study)

Objectives To assess the association between sex and clinical and disease activity indices, and X-rays and magnetic resonance imaging (MRI) features, in early-stage axial spondyloarthritis (axSpA). Method Baseline data analysis was conducted on the Italian SPACE cohort, including patients with chronic back pain (duration ≥ 3 months and ≤ 2 years; onset < 45 years). Patients underwent MRI and X-rays of the sacroiliac joints (SIJs) to establish the diagnosis of axSpA, according to Assessment of SpondyloArthritis international Society criteria and physician’s judgement. Clinical features, disease activity and functional indices, and images were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRI images were scored by two readers following Spondyloarthritis Research Consortium of Canada (SPARCC), modified Stoke Ankylosing Spondylitis Spinal Score, and modified New York criteria. Characteristics of axSpA patients according to sex (male/female) were compared over time using descriptive statistics. Results Ninety-one patients had axSpA (83.5% non-radiographic; 16.5% radiographic); 47.3% were male. Males were younger, with shorter duration of axial symptoms, and more frequently had HLA-B27 positivity, radiographic sacroiliitis with a bilateral/symmetric pattern, and more signs of spondylitis. Females more frequently showed peripheral/entheseal involvement and the non-radiographic phenotype. Males showed increased pelvic/spinal radiographic progression and more often had active sacroiliitis on MRI. Although the frequency of inflammatory corner lesions did not differ between males and females, localization varied, with more cervical/thoracic MRI-spine lesions in females and more lumbar lesions in males. We observed a significant downward trend of SPARCC SIJ/spine scores in all patients, irrespective of sex. More fat lesions were observed on MRI-spine in females and on MRI-SIJ in males. Conclusion Sex was associated with distinct axSpA features: females showed low-grade radiographic sacroiliitis and spinal progression, and a higher prevalence of cervical and thoracic spine MRI signs.

Antibodies of the immunoglobulin a isotype to novel antigens in early axial spondyloarthritis.

There is an unmet need for biomarkers to identify patients with axial spondyloarthritis (axSpA). Increasing evidence suggest the presence of autoantibodies in a subset of axSpA patients. The aim of this study was to identify novel IgA antibodies in early axSpA patients and to determine their diagnostic potential in combination with previously determined IgG antibodies against UH (Hasselt University)-axSpA-IgG antigens. An axSpA cDNA phage display library constructed from axSpA hip synovium, was used to screen for novel IgA antibodies in plasma from early axSpA patients. The presence of these antibodies against novel UH-axSpA-IgA antigens was determined in two independent axSpA cohorts, in healthy controls and in patients with chronic low back pain. We identified antibodies to 7 novel UH-axSpA-IgA antigens, of which 6 correspond to non-physiological peptides and 1 to the human histone deacetylase 3 (HDAC3) protein. IgA antibodies against 2 of these 7 novel UH-axSpA-IgA antigens and IgG antibodies against 2 of the previously identified antigens were significantly more present in early axSpA patients from the UH cohort (18/70, 25.7%) and the (Bio)SPAR cohort (26/164, 15.9%), compared to controls with chronic low back pain (2/66, 3%). Antibodies to this panel of 4 antigens were present in 21.1% (30/142) of patients with early axSpA from the UH and (Bio)SPAR cohorts. The positive likelihood ratio for confirming early axSpA using antibodies to these 4 UH-axSpA antigens was 7.0. So far, no clinical correlation between the novel identified IgA antibodies and inflammatory bowel disease could be identified. In conclusion, screening an axSpA cDNA phage display library for IgA reactivity resulted in the identification of 7 novel UH-axSpA-IgA antigens, of which 2 show promising biomarker potential for the diagnosis of a subset of axSpA patients, in combination with previously identified UH-axSpA-IgG antigens.

Fetuin-A: A Novel Biomarker of Bone Damage in Early Axial Spondyloarthritis. Results of an Interim Analysis of the SPACE Study.

Our study aimed to evaluate the association between fetuin-A levels and the presence of radiographic sacroiliitis and syndesmophytes in patients with early axial spondyloarthritis (axSpA) and to identify potential predictors of radiographic damage in the sacroiliac joints (SIJs) after 24 months. Patients diagnosed with axSpA in the Italian cohort of the SpondyloArthritis-Caught-Early (SPACE) study were included. Physical examinations, laboratory tests (including fetuin-A), SIJ,+ and spinal X-rays and MRIs at T0 (diagnosis) and at T24 were considered. Radiographic damage in the SIJs was defined according to the modified New York criteria (mNY). Fifty-seven patients were included in this analysis (41.2% male, median (interquartile range), chronic back pain [CBP] duration of 12 (8-18) months). Fetuin-A levels were significantly lower in patients with radiographic sacroiliitis compared to those without at T0 (207.9 (181.7-215.9) vs. 239.9 (217.9-286.9), respectively, p < 0.001) and at T24 (207.6 (182.5-246.5) vs. 261.1 (210.2-286.6) µg/mL, p = 0.03). At T0, fetuin-A levels were significantly higher in non-smokers, in patients with heel enthesitis and in those with a family history of axSpA; fetuin-A levels at T24 were higher in females, in patients with higher ESR or CRP at T0 and in those with radiographic sacroiliitis at T0. Fetuin-A levels at T0 were independently negatively associated with the likelihood of radiographic sacroiliitis (OR = 0.9 per 10-unit increase (95% CI 0.8, 0.999), p = 0.048); but not with the presence of syndesmophytes. After adjustment for confounders, fetuin-A levels at T0 and T24 were also negatively associated with mNY at T0 (β -0.5, p < 0.001) and at T24 (β -0.3, p < 0.001), respectively. Among other variables at T0, fetuin-A levels did not achieve statistical significance in predicting mNY at T24. Fetuin-A levels were negatively associated with radiographic damage of the SIJs, but not of the spine, in early axSpA and after 2 years of follow-up. Our findings suggest that fetuin-A levels may serve as a biomarker to identify patients with a higher risk of developing severe disease and early structural damage.

Treatment With Tumor Necrosis Factor Inhibitors Is Associated With a Time-Shifted Retardation of Radiographic Sacroiliitis Progression in Patients With Axial Spondyloarthritis: 10-Year Results From the German Spondyloarthritis Inception Cohort.

To investigate the longitudinal association between radiographic sacroiliitis progression and treatment with tumor necrosis factor inhibitors (TNFi) in patients with early axial spondyloarthritis (SpA) in a long-term inception cohort. We included patients from the German Spondyloarthritis Inception Cohort who underwent radiographic assessment of the sacroiliac joints at baseline and at least once more during the 10-year follow-up. Two central readers scored the radiographs according to the modified New York criteria for ankylosing spondylitis. The sacroiliac sum score was calculated as a mean of the scores determined by both readers. TNFi use was assessed according to exposure in the current and/or previous 2-year radiographic interval. The association between TNFi use and radiographic sacroiliitis progression was examined by longitudinal generalized estimating equation analysis with adjustment for potential confounders. In this long-term inception cohort, 10-year follow-up data on 737 radiographic intervals assessed in 301 patients with axial SpA (166 patients with nonradiographic axial SpA and 135 patients with radiographic axial SpA) were obtained. Having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was associated with a significant decrease in the sacroiliitis sum score (β=-0.09 [95% confidence interval (95% CI) -0.18, -0.003]; analyses adjusted for age, sex, symptom duration, HLA-B27 status, Bath Ankylosing Spondylitis Disease Activity Index score, C-reactive protein, and nonsteroidal antiinflammatory drug intake). In contrast, among patients receiving TNFi in the current radiographic interval, there was no significant association with change in the sacroiliitis sum score (β=0.05 [95% CI -0.05, 0.14]). This effect of having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was stronger in patients with nonradiographic axial SpA as compared to patients with radiographic axial SpA (β=-0.16 [95% CI -0.28, -0.03] versus β=-0.04 [95% CI -0.15, 0.07]). Treatment with TNFi was associated with the reduction in radiographic sacroiliitis progression in patients with axial SpA. This effect became evident between 2 and 4 years after treatment was initiated.

Achievement of clinical-laboratory and ASAS-partial remission in patients with early axial spondyloarthritis according to the ESAC cohort at the 3rd year of follow-up

According to the treat-to-target strategy for spondyloarthritis (SpA), the main goal is to achieve clinical remission or inactive disease. In 2001, the Assessment of Spondyloarhtritis International Society (ASAS) formulated the ASAS criteria for partial remission, and the Russian expert group for the study of SpA identified clinical-laboratory remission (no clinical manifestations of the disease that persists for 6 months in the presence of normal values of C-reactive protein and erythrocyte sedimentation rate), magnetic resonance imaging (MRI) remission and complete remission (a combination of clinical-laboratory and MRI remission). To determine the frequency of achieving clinical-laboratory and ASAS partial remission in patients with early axial SpA (axSpA) at the 3rd year of follow-up. The study included patients from the ESAC cohort (Early SpondyloArthritis Cohort), formed at the Nasonova Research Institute of Rheumatology (Moscow). Currently, the cohort includes 175 patients with axSpA. The analysis included 66 patients followed for at least 3 years, of which 37 (56%) were men and 29 (44%) were women. The average age of the patients was 31.5 (5.7) years, the average duration of the disease was 22.1 (17.0) months, 63 (95.4%) patients had HLA-B27 antigen. Clinical-laboratory remission was achieved by 21 (31.8%) patients with early axSpA at the 3rd year of follow-up, ASAS partial remission by 29 (44.0%) patients. In the 3rd year of follow-up of patients with early axSpA, 32% of patients achieved clinical-laboratory remission, and 44% of patients achieved ASAS partial remission. More than 40% of patients with early axial spondyloarthritis achieve remission while taking non-steroidal anti-inflammatory drugs.

How is early spondyloarthritis defined in the literature? Results from a systematic review

AimTo identify all possible definitions of “early SpA” employed in the literature, including “early axial SpA (axSpA)” and “early peripheral SpA (pSpA)”. MethodsA systematic literature review was conducted in Medline, EMBASE and the Cochrane Library for studies that included any mention of “early SpA” or its subtypes. The proportion of studies including a definition was calculated, and the different definitions were assessed. ResultsOut of 9651 titles identified, 336 publications reporting data from 183 studies were included. Over time, an increasing number of publications were identified. In total, 114 (62%) studies reported a specific definition: 33% of them based it on symptom duration, 31% on radiographic damage, 28% on disease duration, 5% on both symptom/disease duration and radiographic damage, and 3% on other aspects. Overall, 61 (33%) studies included the term “early axSpA”, whereas 60 (33%) included “early ankylosing spondylitis (AS)”. Regarding the studies that referred to “early axSpA”, the most used definition was symptom/disease duration <5 years, whereas for “early AS” was symptom/disease duration <10 years. After 2010, the definition of “early axSpA” based on the absence of radiographic sacroiliitis was less used compared to before 2010 (17% vs 38%). ConclusionOver time, the term “early SpA” and its subtypes is increasingly used. More than one third of the studies did not include a definition of the term and the studies reporting one showed a large heterogeneity. These results emphasize the need for a standardised definition of early SpA.

OP0021 TREATMENT WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IS ASSOCIATED WITH RETARDATION OF RADIOGRAPHIC SPINAL PROGRESSION IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS: 10-YEAR RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT

BackgroundThere are conflicting data regarding effect of nonsteroidal anti-inflammatory drugs (NSAID) on radiographic spinal progression in axial spondyloarthritis (axSpA). The analysis of the first 2-year of the GErman SPondyloarthritis Inception Cohort (GESPIC) showed that higher NSAID intake may retard new bone formation in r-axSpA. It remained, however, unclear, whether cyclooxygenase-2 selective inhibitors (COX2i) might have a stronger effect than non-selective (NS) ones and if the effect could be observed also in nr-axSpA.ObjectivesTo investigate the effect of NSAIDs (COX2i and NS) intake on radiographic spinal progression in patients with r-axSpA and nr-axSpA.MethodsBased on availability of at least two sets of spinal radiographs during 10-year follow-up, 243 patients with early axSpA (130 and 113 nr- and r-axSpA, respectively) from GESPIC were included in this analysis. The patients contributed a total of 540 2-year radiographic intervals. Radiographs were scored by 3 trained and calibrated readers according to modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Final mSASSS was calculated as a mean of 3 readers, and progression was defined as absolute mSASSS change score over 2 years. NSAID type, daily dose, and frequency of intake were recorded at visits. The ASAS index of NSAID intake (0-100) counting both dose and duration of intake was calculated for intervals. The association between NSAID intake (NSAID type and NSAID score) and radiographic spinal progression over 2 years was analysed using longitudinal generalized estimated equations (GEE).ResultsAt baseline, 161 (66.3%) patients were treated with NSAIDs. While 289 (53.5%) and 128 (23.7%) 2-year radiographic intervals were covered by NS and COX-2i respectively, 123 (22.8%) intervals were not covered by NSAID. The significant association between higher NSAID intake and retardation of radiographic spinal progression was found in adjusted multivariable longitudinal GEE analysis. This effect was mostly attributable to patients with r-axSpA (Table 1). mSASSS progression was numerically lower in patients taking COX2i (irrespectively of dose) as compared to patients treated with NS-NSAIDs; in stratified analysis, however, there was no clear dose-dependency (as reflected by NSAID index) in both groups (Figure 1, Table 1).Table 1.The association between radiographic spinal progression (mSASSS change score) and NSAID intake in patients with axSpA in multivariable longitudinal GEEAll axSpA β (95% CI)* (n=461)nr-axSpA β (95% CI)*(n=244)r-axSpA β (95% CI)* (n=217)NSAID intake score, per 10 points-0.04 (-0.09, 0.00)-0.02 (-0.06, 0.02)-0.07 (-0.13, 0.00)NSAID type§ NS inhibitors vs No NSAID0.30(-0.07, 0.66)0.25(-0.07, 0.57)0.26(-0.40, 0.92) COX2i vs No NSAID0.17(-0.19, 0.54)0.15(-0.15, 0.46)0.18(-0.49, 0.85) COX2i vs NS inhibitors-0.12(-0.37, 0.12)-0.10(-0.28, 0.09)-0.08(-0.57, 0.40)Analysis stratified according to NSAID typeNon-selective NSAID intake score, per 10 points-0.06(-0.12, 0.00)-0.04(-0.09, 0.01)-0.07(-0.17, 0.03)COX2 selective NSAID intake score, per 10 points-0.06(-0.13, 0.02)-0.03(-0.07, 0.02)-0.09(-0.18, 0.01)axSpA: axial spondyloarthritis; COX2i, cyclooxygenase-2 selective inhibitors; n, number of current 2-year radiographic intervals in multivariable analyses; NS, non-selective COXi; NSAID, non-steroidal anti-inflammatory drugs.*All multivariable models were adjusted for sex, symptom duration at the beginning of the interval, time-averaged ASDAS the interval, classification as radiographic axSpA, smoking in the interval, mSASSS at the beginning of theinterval, and TNFi use in the interval.§NSAID intake score was added in this model.ConclusionHigher NSAID intake is associated with lower radiographic spinal progression, particularly in r-axSpA patients. COX2i might possess a stronger inhibitory effect on radiographic progression as compared to NS-NSAIDs.Disclosure of InterestsMurat Torgutalp: None declared, Valeria Rios Rodriguez Consultant of: AbbVie, Grant/research support from: Falk e.V, Ani Dilbaryan: None declared, Fabian Proft Speakers bureau: Novartis, Lilly, UCB AbbVie, AMGEN, BMS, Hexal, MSD, Pfizer, Roche and Janssen, Grant/research support from: Novartis, Lilly and UCB, Mikhail Protopopov Consultant of: Novartis and UCB, Maryna Verba: None declared, Judith Rademacher Consultant of: Novartis and UCB, Hildrun Haibel Consultant of: Boehringer, Janssen, MSD, Novartis, Sobi, Roche, Pfizer, AbbVie, and Sobi, Joachim Sieper Speakers bureau: Abbvie, Janssen, Lilly, Merck, Novartis, UCB, Consultant of: AbbVie, Lilly, Merck, Novartis, UCB, Martin Rudwaleit Speakers bureau: AbbVie, Boehringer Ingelheim, Celgen, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB., Consultant of: AbbVie, Boehringer Ingelheim, Celgen, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB., Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer.

Improving the design of RCTs in non-radiographic axial spondyloarthritis.

Concerns have been raised that randomized placebo-controlled trials (RCTs) in non-radiographic axial spondyloarthritis (nr-axSpA) might be failing to identify patients that best show differences in clinical response rates between those receiving active drug and those receiving placebo therapies; in addition, some studies might even be showing spurious differences in responses to TNF and IL-17 inhibitor therapies. In particular, the most recent phase III RCTs in nr-axSpA have reported variable and generally lower response rates than observed in phase III trials of patients with ankylosing spondylitis and in trials conducted a decade ago in patients with early axSpA who were selected on the basis of axial inflammation evident on MRI scans. We argue that these observations at least partly reflect an RCT design that does not take full advantage of MRI to select patients who are responsive to therapy because the current MRI-based inclusion criteria cannot identify patients with axSpA with sufficient specificity. We propose that future studies should be designed using revised patient inclusion criteria based on expanded MRI evaluation and the application of data-driven definitions of a positive MRI for inflammatory and structural lesions typical of axSpA reported in an international multicentre analysis of MRI scans from the Assessment of SpondyloArthritis International Society (ASAS) classification cohort.

Opioid use frequency in early axial spondyloarthritis in Finland-a pharmacoepidemic register study.

To evaluate opioid use among incident axial spondyloarthritis (axSpA) patients compared to general population. From the national register, we identified all adult patients with axSpA (ICD-10 codes M45-46), who between 2010 and 2014 (index date, ID) were for the first time granted special reimbursement for any disease-modifying antirheumatic drugs (DMARDs). Three matched population controls were identified for each patient. Drug purchases were evaluated between 2009-2015, and opioid use was analyzed for one year before and after the ID. The Defined Daily Dose (DDD) was used as a tool to assess the opioid consumption before and after the biological (b) DMARD initiation. We identified 3577 axSpA patients and 10,573 controls. Of these patients, 97.2% started a conventional synthetic (cs) DMARD during a year after ID and 23.4% switched later to a self-injected bDMARD between the ID and 31 Dec 2015 (median follow-up 3.4 years). Opioids were purchased at least once by 29.8% and 21.7% of the patients in the years before and after the ID, respectively, compared to 8.1% and 7.8% of the controls. The proportion of opioid-using patients was greatest during the last quarter before the ID [relative risk (RR) 4.72 (95% CI 4.14 to 5.39)] compared to controls, and it remained higher [RR 2.84 (2.59 to 3.11)] also after the start of csDMARDs. DDD of opioid consumption decreased from 7.7 to 1.6/1000 inhabitants after bDMARD initiation. Considerably more axSpA patients than population controls used opioids. The opioid consumption by dose decreased clearly after bDMARD initiation.

P261 Early and accurate diagnosis of patients with axial spondyloarthritis using machine learning: a predictive analysis from electronic health records in the United Kingdom

Abstract Background/Aims On average, there is a delay of 6.7 years between symptom onset and diagnosis of axial spondyloarthritis (axSpA). Since traditional approaches to improving early axSpA identification have had limited success, predictive automated analyses using patient records may help alleviate the burden on healthcare providers. We report results from a machine learning (ML) algorithm developed with UK electronic health records (EHRs) Clinical Practice Research Datalink (CPRD) data to estimate the probability or likelihood of a patient being diagnosed with axSpA based on prior clinical indicators and patient history. Methods Primary care UK EHR data - CPRD GOLD was used to identify patients with axSpA and healthy controls (HC). Patients aged ≥18 years with first diagnosis date of axSpA within the identification period (01-Jan-2005 to 31-Dec-2018) and fulfilling CPRD research acceptability criteria were included. Data pertaining to clinical presentation, consultation, referral, test, and therapy history were extracted for individual patients prior to diagnosis of axSpA. A total of 5,090 patients with axSpA satisfied the acceptability criteria. HC were randomly sampled to create a subset of one unique HC matched to each patient with axSpA, resulting in 5,089 HC. ML usable features derived from the total population (patients with axSpA and HC) numbered 820. After using a further exclusion criterion for the patients with axSpA and HC who had ≥1 of 820 usable features, the final dataset included 7,813 patients (3,902 with axSpA and 3,911 HC). This combined dataset was randomly split (67:33) into a train (n = 5237) and a test (n = 2576) dataset. A random forest (RF) model was trained on the train dataset. Cross-validation was performed for hyper-parameter tuning of the RF classifier. Once the model was trained, accuracy, precision, and F-1 scores were obtained with the test dataset. Results The RF-based algorithm resulted in a high level of accuracy (88.12%), with precision of 0.95 for patients with axSpA and 0.83 for HC. The RF algorithm identified 89 best clinical predictors (out of 820 used as inputs) that differentiated between patient and HC such as: total number of tests, total number of referrals, first age of consultation, first symptom age, and number of low back pain symptoms. The model sensitivity was 0.75 and positive predictive value was 80.88%. The model specificity was 0.96 and negative predictive value was 82.56%. Conclusion The ML algorithm demonstrated a high level of accuracy and precision in the identification of possible cases of axSpA, which may be useful in reducing the delay in diagnosis. Previous studies have successfully demonstrated automated cohort identification of axSpA in large datasets, with only a few using ML-based approaches for diagnosis from patient medical history. While our model supports previous work in axSpA, it needs further validation in routine clinical practice (exploration ongoing). Disclosure R. Sengupta: Honoraria; AbbVie, Biogen, Celgene, Lilly, MSD, Novartis, Roche, UCB. Grants/research support; AbbVie, Celgene, Novartis, UCB. S. Narasimham: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. B.S. Mato: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. M. Meglic: Other; Employee of Novartis. C. Perella: Other; Employee of Novartis. P. Pamies: Other; Employee of Novartis. P. Emery: Consultancies; AbbVie, Astra-Zeneca, BMS, Boehringer Ingelheim, Celltrion, Gilead, Janssen, MSD, Lilly, Novartis, Pfizer, Roche, Samsung, UCB. Grants/research support; AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, Samsung.

Machine-learning derived algorithms for prediction of radiographic progression in early axial spondyloarthritis.

To compare machine learning (ML) to traditional models to predict radiographic progression in patients with early axial spondyloarthritis (axSpA). We carried out a prospective French multicentric DESIR cohort study with 5 years of follow-up that included patients with chronic back pain for <3 years, suggestive of axSpA. Radiographic progression was defined as progression at the spine (increase of at least 1 point of mSASSS scores/2 years) or at the sacroiliac joint (worsening of at least one grade of the mNY score between 2 visits). Statistical analyses were based on patients without any missing data regarding the outcome and variables of interest (295 patients).Traditional modelling: we performed a multivariate logistic regression model (M1); then variable selection with stepwise selection based on Akaike Information Criterion (stepAIC) method (M2), and Least Absolute Shrinkage and Selection Operator (LASSO) method (M3).ML modelling: using "SuperLearner" package on R, we modelled radiographic progression with stepAIC, LASSO, random forest, Discrete Bayesian Additive Regression Trees Samplers (DBARTS), Generalized Additive Models (GAM), multivariate adaptive polynomial spline regression (polymars), Recursive Partitioning And Regression Trees (RPART) and Super Learner. Accuracy of these models was compared based on their 10-fold cross-validated AUC (cv-AUC). 10-fold cv-AUC for traditional models were 0.79 and 0.78 for M2 and M3, respectively. The three best models in the ML algorithms were the GAM, the DBARTS and the Super Learner models, with 10-fold cv-AUC of: 0.77, 0.76 and 0.74, respectively. Two traditional models predicted radiographic progression as good as the eight ML models tested in this population.

Differences in topographical location of sacroiliac joint MRI lesions in patients with early axial spondyloarthritis and mechanical back pain

BackgroundEarly diagnostics of axial spondyloarthritis (axSpA) remains a challenge. Traditional imaging one-plane sacroiliac joint (SIJ) MRI assessment is used. By introducing a two-plane assessment system, the objective was to analyse the differences in SIJ MRI changes in early axSpA compared with changes in patients with mechanical back pain (MBP) by exploring the differences in volume and location.MethodsMRIs in the early diagnostic state of 25 axSpA patients (mean age 31.3 years) and 59 MBP patients (mean age 32.3 years) were included. The MRIs were assessed by two readers regarding the distribution of bone marrow edema (BME) in 14 joint portions and structural changes in six joint portions in addition to SIJ anatomical variations and lumbar spine disc degeneration.ResultsAxSpA patients had a significantly higher overall BME sumscore (volume) of 25.1 compared to MBP patients 6.8, p < 0.005. The MBP group had the highest prevalence (66%) and sumscore (5.7) in the middle anterior sacrum. The axSpA group had significantly higher prevalence and sumscores in all joint portions except the three cartilaginous anterior sacral joint portions, including the ligamentous compartments (prevalence 40–60% compared to 8–15%, p both < 0.005). The axSpA group had also a significantly higher prevalence of erosions and fatty marrow disposition, but there were no differences in the prevalence of anatomical variations except the bipartite iliac bony plate.ConclusionsAxSpA patients demonstrated a widespread distribution of both inflammatory and structural changes, including high BME occurrence in the ligamentous joint portions whereas patients with MBP had the highest occurrence of BME in the middle anterior sacrum. These findings may help differentiate axSpA patients from other back pain conditions in the early diagnostic phase.