Spinal Radiographic Progression Research Articles

Disease modification in axial spondyloarthritis - still a controversy?

This review evaluates recent advancements in disease-modifying therapies for axial spondyloarthritis (axSpA). A recent study could not demonstrate an additional effect of NSAID therapy on golimumab [Tumor Necrosis Factor-α inhibitor (TNFi)] on structural progression; however, this might be due to the fact that the study was underpowered. While DMARDs have shown promise in suppressing inflammation, their impact on structural progression remains uncertain. A well powered trial showed no difference in spinal progression between secukinumab [Interleukin17A inhibitor (IL17Ai)] and adalimumab-biosimilar (TNFi). Preliminary data on Janus kinase inhibitors (JAKi) focus on MRI findings but lack evidence on radiographic spinal progression. While some studies suggest promising outcomes, others reveal limitations and inconclusive findings. Recent studies explore the effectiveness of NSAIDs, biological disease-modifying antirheumatic drugs like TNFi and IL-17i, as well as JAK inhibitors in axSpA. Conflicting evidence surrounds these therapies' ability to impede structural progression, with challenges in study design and interpretation. Moreover, changes in demographics and treatment methods underscore the importance of examining trends over time when assessing disease outcomes. Ultimately, ongoing research could benefit from new imaging tools when evaluating therapeutic strategies for modifying disease progression in axSpA.

Effect of Secukinumab Versus Adalimumab Biosimilar on Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: Results From a Head-to-Head Randomized Phase IIIb Study.

Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was tocompare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; tumor necrosis factor inhibitor). Biologic-naive patients with active radiographic axial SpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ-ADL at week 104 (primary endpoint), mean CFB-mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ-ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB-mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ-ADL arms. The safety of both treatments was consistent with previous reports.

Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial

ObjectivesThe study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on...

The Effect of Two Years of Secukinumab Treatment on Bone Metabolism in Patients with Radiographic Axial Spondyloarthritis: Results from Daily Clinical Practice.

Our objective was to explore bone-related outcome and bone turnover markers (BTM) during 2 years of secukinumab treatment in patients with radiographic axial spondyloarthritis (r-axSpA) in daily clinical practice. Included were consecutive r-axSpA outpatients from the Groningen Leeuwarden axSpA (GLAS) cohort treated with secukinumab for 2 years. At baseline and 2 years, spinal radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; 0-72), cervical facet joint involvement according the "de Vlam" scoring method (0-15) and radiographic vertebral fractures (VF) using the "Genant" method (grade 0-3). At all visits, BTM reflecting collagen resorption (serum type I collagen C-telopeptide; sCTX), collagen formation (procollagen type 1 N-terminal peptide; PINP) and bone mineralization (bone-specific alkaline phosphatase; BALP) were measured and expressed in Z-scores to correct for the normal influence of age and gender. 17 r-axSpA patients were included; 53% male, mean age was 47±15 years, mean Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.9±1.2, and 53% was biological naïve. The median 2-year progression rates were 1.1 for mSASSS and 0.5 for facet joints, which was less than the smallest detectable change. One traumatic VF (grade 3) occurred. Serum levels of sCTX and PINP remained stable during secukinumab treatment and BALP decreased significantly after 2 years, with median 0-2 year change in Z-scores of +0.1, -0.4, and -1.2, respectively. This explorative study of r-axSpA patients treated with secukinumab in daily clinical practice showed low radiographic spinal progression during 2 years of follow-up. Collagen resorption and formation markers remained stable, whereas mineralization marker BALP decreased significantly after 2 years. Our results are in line with the results of in vitro studies demonstrating that inhibition of IL17-A resulted in suppression of osteogenic differentiation with significant decrease in mineralization.

Impact of sex on spinal radiographic progression in axial spondyloarthritis: a longitudinal Swiss cohort analysis over a period of 10 years

ObjectiveTo investigate sex differences in spinal radiographic progression in axial spondyloarthritis (axSpA).MethodsAxSpA patients in the Swiss Clinical Quality Management cohort with available spinal radiographs every 2 years were included. Paired...

Anaemia is associated with higher disease activity in axial spondyloarthritis but is not an independent predictor of spinal radiographic progression: data from the Swiss Clinical Quality Management Registry

ObjectiveAs anaemia represents a biomarker for increased radiographic damage in rheumatoid arthritis, we aimed to investigate whether it independently predicts spinal radiographic progression in axial spondyloarthritis (axSpA).MethodsAxSpA patients with available haemoglobin levels from the prospective Swiss Clinical Quality Management Registry were included for comparison of patients with and without anaemia. Spinal radiographic progression was assessed according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in patients with ankylosing spondylitis (AS) if ≥ 2 sets of spinal radiographs were available every 2 years. The relationship between anaemia and progression (defined as an increase ≥ 2 mSASSS units in 2 years) was analysed with generalized estimating equation models after adjustment for the Ankylosing Spondylitis Disease Activity Score (ASDAS) and potential confounding, as well as after multiple imputations of missing values.ResultsA total of 212/2522 axSpA patients presented with anaemia (9%). Anaemic patients had higher clinical disease activity, higher acute phase reactants and more severe impairments in physical function, mobility and quality of life. In the subgroup of patients with AS (N = 433), a comparable mSASSS progression was found in anaemic and non-anaemic patients (OR 0.69, 95% CI 0.25 to 1.96, p = 0.49). Age, male sex, baseline radiographic damage and ASDAS were associated with enhanced progression. The results were confirmed in complete case analyses and with progression defined as the formation of ≥ 1 syndesmophyte in 2 years.ConclusionAlthough anaemia was associated with higher disease activity in axSpA, it did not additionally contribute to the prediction of spinal radiographic progression.Key Points• Anaemia is associated with higher disease activity and more severely impaired physical function, mobility and quality of life in axSpA.• Anaemia does not provide an additional value to ASDAS for prediction of spinal radiographic progression.

Spinal radiographic progression is correlated with preclinical atherosclerosis in spondyloarthritis.

A higher prevalence of cardiovascular risk was observed in spondyloarthritis (SpA). The relationship between disease-related factors structural damage and subclinical atherosclerosis is still unknown. The aim of our study was to evaluate the association of subclinical atherosclerosis with radiographic structural damage in patients with SpA. Forty-seven SpA patients who fulfilled the ASAS criteria were enrolled in a case-control study conducted over 12months and compared with 47 age and sex-matched healthy controls. None of the subjects had a previous history of cardiovascular diseases or cardiovascular risk factors. Demographic and disease characteristics were recorded. Structural lesions were evaluated using plain radiography, and two scoring tools were used to spine (BASRI and mSASSS). Subclinical atherosclerosis was assessed using ultrasound measurements of flow-mediated dilation (FMD) and carotid intima-media thickness (cIMT). The median age of patients was 36 years. The sex ratio was 2.35. The median BASRI total score was 3 (IQR 2-4), median mSASSS score was 10 (IQR 415). cIMT was significantly increased in SpA patients compared to controls (p< 0.0001), and FMD was significantly lower in patients than in healthy subjects (p= 0.008). cIMT was significantly associated with ankylosis of the facet joints (p= 0.035) and Romanus spondylitis (p= 005). FMD was negatively associated with vertebral squaring (p= 0049), bridging syndesmophytes (p= 0031) and mSASSS score (p= 0.047). Our result supports the association of radiographic structural damage and subclinical atherosclerosis assessed using cIMT and FMD. This finding highlights the importance of earlier treatment in order to prevent radiographic damage progression and atherosclerotic events.

Site-specific assessment of spinal radiographic progression improves detection of TNF blocker-associated disease modification in axial spondyloarthritis: longitudinal observational data from the Swiss Clinical Quality Management Registry

ObjectivesTo analyse whether time-varying treatment with tumour necrosis factor inhibitors (TNFi) in radiographic axial spondyloarthritis (r-axSpA) has a differential impact on structural damage progression on different spinal segments (cervical versus lumbar spine).MethodsPatients with r-axSpA in the Swiss Clinical Quality Management cohort were included if cervical and lumbar radiographs were available at intervals of 2 years for a maximum of 10 years. Paired radiographs were scored by two calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The relationship between TNFi use and progression in the cervical and the lumbar spine was analysed using generalised estimating equation models and adjustment for potential confounding. Radiographic progression per spinal segment was defined as an increase of ≥ 1 mSASSS unit or by the formation of ≥ 1 new syndesmophyte over 2 years.ResultsMean ± SD symptom duration was 13.8 ± 9.8 years. Mean ± SD mSASSS progression per radiographic interval was 0.41 ± 1.69 units in the cervical spine and 0.45 ± 1.45 units in the lumbar spine (p = 0.66). Prior use of TNFi significantly reduced the odds of progression in the cervical spine by 68% (OR 0.32, 95% CI 0.14–0.72), but not in the lumbar spine (OR 0.99, 95% CI 0.52–1.88). A more restricted inhibition of progression in the lumbar spine was confirmed after multiple imputation of missing covariate data (OR 0.43, 95% CI 0.24–0.77 and 0.85, 95% CI 0.51–1.41, for the cervical and lumbar spine, respectively). It was also confirmed with progression defined as formation of ≥ 1 syndesmophyte (OR 0.31, 95% CI 0.12–0.80 versus OR 0.56, 95% CI 0.26–1.24 for the cervical and lumbar spine, respectively).ConclusionDisease modification by treatment with TNFi seems to more profoundly affect the cervical spine in this r-axSpA population with longstanding disease. Site-specific analysis of spinal progression might, therefore, improve detection of disease modification in clinical trials in axSpA.

Knowledge mapping of biological disease-modifying anti-rheumatic drugs for axial spondyloarthritis: a bibliometric study.

Various biological disease-modifying anti-rheumatic drugs (bDMARDs) have been applied for treating axial spondyloarthritis (axSpA). However, there is a glaring absence of a bibliometric analysis on bDMARDs against axSpA. Articles related to use of bDMARDs in treating axSpA published from 2004 to 2022 were searched from the Web of Science Core Collection. VOS viewer 1.6.18 and CiteSpace 6.1.R2 were used to analyze and visualize the quantity and citations of publications, as well as to identify "research hotspots" and trends in this field. BibExcel version 1.0.0 and gCLUTO version 1.0 were used to build matrices for bi-clustering analysis. A total of 2546 articles referring to bDMARDs for treatment of axSpA were included in this bibliometric analysis. Overall, the number of publications has been increasing steadily annually. The USA (23.21%, 591 publications) ranked first with the largest output of papers, followed by Germany, and the Netherlands. Rheumazentrum Ruhrgebiet ranked first as the most frequent publisher (119 articles). Annals of the Rheumatic Diseases published the most documents (6.76%, 172 publications) in this field. The predominant hotspots have been "tuberculosis," "IL-17," and "quality of life" in the field until 2020. Since 2015, "biosimilar pharmaceuticals" has retained the popularity. Current research hotspots are "spinal radiographic progression," Janus kinase (JAK) inhibitors, and adverse events (AEs). Machine learning has become popular gradually. Globally, there has been a steady increase in the number of studies on bDMARDs use against axSpA. JAK inhibitors, spinal radiographic progression, biosimilar pharmaceuticals, and AEs are current research hotspots. Machine learning is emerging research hotspots and trends in this field.

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.

The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences

BackgroundMale HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are unclear. We recently showed that persistently elevated Lipocalin 2 (LCN2; L) reflects sacroiliac joint (SIJ) inflammation. LCN2 binds to MMP9. Concomitant elevation of L and LCN2-MMP9 (LM) was detected in many inflammatory diseases. We asked whether L and LM play similar roles in r-axSpA pathogenesis.MethodsWe analyzed 190 axSpA patients (123 radiographic and 67 non-radiographic axSpA) who had no detectable circulating Oncostatin M, to avoid complications due to cross-talk between pathways. L and LM levels from a single blood sample of each patient were measured and were correlated with MRI and modified stoke AS (mSASS) scoring. Association of elevated L (L+) or concurrent L+ and elevated LM (LM+) patterns with B27 status and gender were assessed.ResultsIn L+LM+ axSpA patients, both L and LM levels correlated with MRI SPARCC SIJ scores, but only LM levels correlated with MRI Berlin Spine Scores, suggesting LM is a biomarker for both SIJ and spinal inflammation. Among patients with minimal spinal ankylosis (mSASSS < 10), 65% of male r-axSpA patients are L+LM+, while 30% and 64% of female patients are L+LM+ and L+, respectively, supporting the role of LM with disease progression. In B27+ L+LM+ male patients, both L and LM (but not CRP) levels correlate with mSASSS. B27 positivity and maleness have additive effects on spondylitis progression, suggesting concurrent high L and LM elevations are associated with B27+ male patients having more significant radiographic damage. L+ B27-negative male patients or L+ female patients are more likely to have milder disease.ConclusionL and LM are informative biomarkers for SIJ and spinal inflammation, as well as for ankylosing development in r-axSpA patients. Distinctive L+LM+ or L+ patterns not only could distinguish clinically aggressive vs milder course of disease, respectively, but also provide an explanation for B27-positive male patients being the most susceptible to severe ankylosis.

Treatment with tumour necrosis factor inhibitors is associated with a time-shifted retardation of radiographic spinal progression in patients with axial spondyloarthritis

ObjectiveThe objective of the current study was to analyse the association between treatment with tumour necrosis factor inhibitors (TNFi) and radiographic spinal progression in patients with axial spondyloarthritis (axSpA) from...

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.

OP0018 COMPARISON OF THE EFFECT OF TREATMENT WITH NSAIDs ADDED TO ANTI-TNF THERAPY VERSUS ANTI-TNF THERAPY ALONE ON PROGRESSION OF STRUCTURAL DAMAGE IN THE SPINE OVER TWO YEARS IN PATIENTS WITH ANKYLOSING SPONDYLITIS (CONSUL) – AN OPEN-LABEL, RANDOMIZED CONTROLLED, MULTICENTER TRIAL

BackgroundThere is some evidence that NSAIDs, in particular celecoxib (CEL), might possess not only symptomatic efficacy but also disease-modifying properties in radiographic axial spondyloarthritis (r-axSpA) formerly known as ankylosing spondylitis, retarding progression of structural damage in the spine if taken continuously. For biological disease-modifying antirheumatic drugs (bDMARDs), retardation of structural damage progression has also been demonstrated, but at least 4 years of treatment seem to be necessary (at least for tumour necrosis factor inhibitors – TNFi) to see such an effect. Therefore, a combination of an NSAID with a TNFi might bring additional benefits in terms of retardation of structural damage progression especially in high-risk patients.ObjectivesThe aim of this RCT was to evaluate the impact of treatment with the COX-II-selective NSAID (CEL) when added to a TNFi (golimumab - GOL) compared with TNFi (GOL) alone on progression of structural damage in the spine over 2 years in patients with r-axSpA.MethodsEligible patients had r-axSpA and high disease activity (BASDAI ≥4), NSAID failure and risk factors for radiographic spinal progression: C-reactive protein &gt;5 mg/l and/or ≥1 syndesmophyte(s). The trial consisted of two phases: a 12-week run-in phase, in which all included patients received treatment with GOL 50 mg every 4 weeks sc, followed by a 96-week controlled treatment period, in which patients who achieved a BASDAI improvement of ≥2 points were randomly assigned to GOL + CEL 200 mg bid or GOL alone arms. The primary endpoint was radiographic spinal progression as assessed by the change in the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) after 108 weeks in the intent-to-treat population, read by 3 independent readers blinded for the treatment arm and the time-point.ResultsOf the 157 screened patients, 81.5% (n=128) were enrolled into the run-in phase. 109 patients fulfilled the BASDAI response criterion at w12 and were randomized 1:1 (54 vs. 55) to GOL+CEL or GOL alone; 97 (45 vs. 52) patients completed the study at w108. Clinical characteristics of the randomized patients are shown in Tab. 1. The mSASSS change after w108 was 1.1 (95%CI 0.2; 2.0) vs. 1.7 (95%CI 0.8; 2.6) in the GOL+CEL vs. GOL alone groups, respectively, p=0.79. Figure 1 shows the cumulative probability of the mSASSS change in both treatment arms. New syndesmophytes in the opinion of three readers occurred in 11% vs. 25% of the patients in the GOL+CEL vs. GOL alone groups, respectively, p=0.12. During the study, a total of 14 serious adverse events (SAE) were reported (7 in the GOL+CEL group, 5 in the GOL alone group and 2 during the run-in phase).Figure 1.Cumulative probability plot of mSASSS progression over 108 weeks of treatment.ConclusionIn this study, a combined therapy with GOL+CEL did not show significant superiority over GOL monotherapy in retarding radiographic spinal progression over two years in r-axSpA patients.However, the observed numerical reduction in radiographic spinal progression associated with the combined treatment might be, however, clinically relevant for patients at high risk for progression.Table 1.Baseline characteristics of randomized patientsParametersGOL+CEL N=54GOL alone N=55All patients N=109validnvaluevalidnvaluevalidnvalueSex, malen (%)5440 (74.1)5541 (74.5)10981 (74.3)Age, yearsMean (SD)5439.9 (9.9)5537.5 (10.8)10938.7 (10.4)Smokern (%)5319 (35.8)5522 (40)10841 (38)HLA-B27 positivityn (%)5445 (83.3)5147 (92.2)10592 (87.6)BASDAIMean (SD)546.2 (1)556.1 (1.1)1096.1 (1.1)BASMIMean (SD)542.6 (1.9)542.9 (1.4)1082.8 (1.6)CRP &gt; 5 mg/Ln (%)5438 (70.4)5538 (69.1)10976 (69.7)ASDAS-CRPMean (SD)543.6 (0.6)553.7 (0.9)1093.7 (0.8)Prior bDMARDsn (%)5417 (31.5)559 (16.4)10926 (23.9)Presence of ≥ 1 syndesmophyte(s)n (%)5427 (50)5528 (50.9)10955 (50.5)mSASSSMean (SD)5413.5 (16.9)5510.3 (13.2)10911.9 (15.2)AcknowledgementsThe CONSUL study has been supported by a grant from the German Ministry of Education and Research (BMBF), grant number FKZ 01KG1603 and study medication (golimumab) was provided free of charge by MSD Sharp &amp; Dohme GmbH, Munich, Germany.Furthermore we would like to thank Anne Weber, Bianca Mandt, Claudia Lorenz, Hildrun Haibel, Judith Rademacher, Laura Spiller, Petra Tietz as well as all participating rheumatologist and included patients.Disclosure of InterestsFabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, UCB, Lilly, Burkhard Muche Speakers bureau: UCB Pharma, AMGEN, Consultant of: UCB Pharma, AMGEN, Valeria Rios Rodriguez Speakers bureau: AbbVie, Falk e.V., Murat Torgutalp: None declared, Mikhail Protopopov Consultant of: Novartis, Joachim Listing: None declared, Maryna Verba: None declared, Uta Kiltz: None declared, Jan Brandt-Juergens: None declared, Maren Sieburg: None declared, Swen Holger Jacki: None declared, Joachim Sieper Speakers bureau: AbbVie, Janssen, Merck, Novartis, Consultant of: Abbvie, Janssen, Lilly, Merck, Novartis, 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, and Pfizer.

Baseline serum biomarkers of inflammation, bone turnover and adipokines predict spinal radiographic progression in ankylosing spondylitis patients on TNF inhibitor therapy

ObjectiveTo analyze whether biomarker levels at baseline or their change after 3 months or 2 years predict radiographic spinal progression in ankylosing spondylitis (AS) patients treated with TNF-α inhibitors (TNFi). Methods137 AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included before starting TNFi. Serum biomarkers were measured at baseline, 3 months and 2 years: Markers of inflammation (calprotectin, matrix metalloproteinase-3, vascular endothelial growth factor), bone turnover markers (bone-specific alkaline phosphatase, serum C-terminal telopeptide fragments of type I collagen (sCTX), osteocalcin, osteoprotegerin, procollagen type I and II N-terminal propeptide, sclerostin) and adipokines (high-molecular-weight adiponectin, leptin, visfatin). Spinal radiographs were scored at baseline, 2 and 4 years. Logistic regression was performed to examine the association between biomarker values and radiographic spinal progression, adjusting for known risk factors for radiographic progression. ResultsBaseline calprotectin and visfatin levels were associated with mSASSS progression ≥2 points (OR 1.195 [95%CI 1.055–1.355] and 1.465 [1.137–1.889], respectively), while calprotectin was also associated with new syndesmophyte formation after 2 years (OR 1.107 [1.001–1.225]). Baseline leptin level was associated with mSASSS progression ≥4 points after 4 years (OR 0.614 [0.453–0.832]), and baseline sCTX level with syndesmophyte formation after 4 years (OR 1.004 [1.001–1.008]). Furthermore, change of visfatin and leptin levels over the first 2 years showed significant association with radiographic progression after 4 years. ConclusionIndependent of known risk factors, serum levels of biomarkers at baseline are able to predict radiographic spinal progression over 2 and 4 years in AS patients on TNFi therapy.

Current differentiation between radiographic and non-radiographic axial spondyloarthritis is of limited benefit for prediction of important clinical outcomes: data from a large, prospective, observational cohort

ObjectiveTo compare disease characteristics and outcomes between patients with axial spondyloarthritis with non-radiographic disease (nr-axSpA), bilateral grade 2 sacroiliitis (r22axSpA) and unilateral/bilateral grade 3–4 sacroiliitis (r3+axSpA) according to the modified...

Sustained low disease activity measured by ASDAS slow radiographic spinal progression in axial spondyloarthritis patients treated with TNF-inhibitors: data from REGISPONSERBIO

BackgroundTo evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi).MethodsThe study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (≥4 years) and (ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients’ groups at each time point were assessed using a linear mixed-effect model.ResultsRadiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP).ConclusionsPatients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.

Zoledronic acid does not slow spinal radiographic progression of osteoarthritis in postmenopausal women with osteoporosis and radiographic osteoarthritis.

Introduction:Post hoc analyses of osteoporosis trials have suggested that alendronate and strontium ranelate may be associated with a reduction in the progression of spinal radiographic osteoarthritis (OA). We performed an analysis on a subgroup of participants in the horizon PFT trial (a 3-year randomized controlled trial (RCT) of yearly zoledronic acid (ZA) in postmenopausal women with osteoporosis), to evaluate the effect of ZA on the structural progression of spinal osteophytes (OPh) and disk space narrowing (DN).Methods:Paired lateral spinal X-rays (baseline and 36 months) were selected from the horizon PFT trial records restricted to those with radiographic OA at baseline. The X-rays were analyzed by two readers blinded to the treatment allocation. OPh and DN were scored separately using the Lane atlas (0–3 for increasing severity at each vertebral level) at all evaluable levels from T4–12 and L1–5.Results:A total of 504 sets of paired radiographs were included in the analysis, 245 in the ZA group and 259 in the placebo group. Overall, the rates of change of OPh and DN scores were low, and they were not statistically different between the groups (change in the whole spine OPh ZA 1.0 ± 1.6, placebo 0.8 ± 1.3, p = 0.1; DN ZA 0.3 ± 1.0, placebo 0.3 ± 0.8, p = 0.7).Conclusion:Yearly ZA for 3 years was not associated with a slowing of progression of OPh or DN in the thoracolumbar spine in patients with pre-existing radiographic OA.

Age-stratified trends in the progression of spinal radiographic damage in patients with ankylosing spondylitis: a longitudinal study.

Objective:The objective of this study was to investigate spinal radiographic progression in specific age ranges of ankylosing spondylitis (AS) patients.Methods:Longitudinal data for 1125 AS patients at a single hospital from 2000 to 2018 were retrospectively reviewed. Radiographic intervals were obtained from patients with consecutive spinal radiographs. The radiographic progression rate was defined as the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change per year within each interval. Using generalized estimating equations (GEEs), estimated marginal means were calculated for the mSASSS progression rate across age groups after adjusting for potential confounders.Results:We obtained 4016 radiographic intervals and stratified them into five groups based on patient age at the interval start: <20 (n = 122); 20–29 (n = 1124); 30–39 (n = 1690); 40–49 (n = 794); and ⩾50 years (n = 286). The mean (SD) mSASSS progression rate for all the intervals was 0.8 (1.9). The GEE-estimated mean mSASSS progression rate increased with age, peaking in the 30–39 age group with a value of 1.15 [95% confidence interval (CI) 1.03, 1.27], and decreased slightly thereafter. In the presence of risk factors, rapid progression occurred at earlier ages: the GEE-estimated mean mSASSS progression rate in those with elevated C-reactive protein levels and preexisting syndesmophytes was 2.82 (95% CI 1.93, 3.71) in the 20–29 age group.Conclusion:Spinal structural damage in AS seems to progress most rapidly when patients are age 30–39 years. An awareness of the trends in radiographic progression with advancing age could improve understanding of the natural course of AS.

Early control of C-reactive protein levels with non-biologics is associated with slow radiographic progression in radiographic axial spondyloarthritis.

Predicting radiographic progression is vital for assessing the prognosis of patients with radiographic axial spondyloarthritis, and C-reactive protein (CRP) may be a valuable biomarker for this purpose. This study aimed to investigate the relationship between changes in the CRP level and spinal radiographic progression in patients with radiographic axial spondyloarthritis who were initially treated with non-biologics. Patients with radiographic axial spondyloarthritis who were followed up for 18years at a single center and initially treated with nonsteroidal anti-inflammatory drugs and/or conventional disease-modifying antirheumatic drugs for 3months were included. Patients with a CRP level of <0.8mg/dL or 50% of the baseline CRP at 3months were assigned to the controlled CRP group (n=351), and the remaining patients were assigned to the uncontrolled CRP group (n=452). A generalized estimating equation was used to analyze the differences in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between the 2 groups. The increase in the mSASSS was slower in the controlled CRP group than in the uncontrolled CRP group (interaction term β=-.499, 95% confidence interval -0.699 to -0.300). Controlled CRP achieved in response to initial treatment with non-biologic agents for 3months was significantly associated with a slower rate of spinal radiographic change in patients with radiographic axial spondyloarthritis. The CRP level at 3months after initial non-biologic treatment is a good predictor of radiographic progression.