results from the German Spondyloarthritis Inception Cohort

Background Functional status and spinal mobility in patients with axial spondyloarthritis (axSpA) are known to be determined both by disease activity and by structural damage in the spine. The impact of structural damage in the sacroiliac joints (SIJ) on physical function and spinal mobility in axSpA has not been studied so far. The objective of the study was to analyze the impact of radiographic sacroiliitis on functional status and spinal mobility in patients with axSpA. Methods In total, 210 patients with axSpA were included in the analysis. Radiographs of SIJ obtained at baseline and after 2 years of follow up were scored by two trained readers according to the modified New York criteria grading system (grade 0–4). The mean of two readers’ scores for each joint and a sum score for both SIJ were calculated for each patient giving a sacroiliitis sum score between 0 and 8. The Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) at baseline and after 2 years were used as outcome measures. Results Longitudinal mixed model analysis adjusted for structural damage in the spine (modified Stoke Ankylosing Spondylitis Spine Score - mSASSS), disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI and C-reactive protein level) and gender, revealed an independent association of the sacroiliitis sum score with the BASFI: b = 0.10 (95% CI 0.01–0.19) and the BASMI: b = 0.12 (95% CI 0.03–0.21), respectively, indicating that change by one radiographic sacroiliitis grade in one joint is associated with BASFI/BASMI worsening by 0.10/0.12 points, respectively, independently of disease activity and structural damage in the spine. Conclusion Structural damage in the SIJ might have an impact on functional status and spinal mobility in axSpA independently of spinal structural damage and disease activity. Trial registration ClinicalTrials.gov, NCT01277419. Registered on 14 January 2011

Study protocol: Comparison of the effect of treatment with Nonsteroidal anti- inflammatory drugs added to anti-tumour necrosis factor a therapy versus anti- tumour necrosis factor a 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

Introduction There is some evidence that non-steroidal anti-inflammatory drugs (NSAIDs), in particular celecoxib, might possess not only a symptomatic efficacy but also disease-modifying properties in ankylosing spondylitis (AS), retarding the progression of structural damage in the spine if taken continuously. In contrast, this remains controversial for tumour necrosis factor alpha (TNF-α) inhibitors, despite their good clinical efficacy. The impact of a combined therapy (a TNF inhibitor plus an NSAID) on radiographic spinal progression in AS is unclear. Methods and analysis The aim of this study is to evaluate the impact of treatment with an NSAID (celecoxib) when added to a TNF inhibitor (golimumab) compared with TNF inhibitor (golimumab) alone on progression of structural damage in the spine over 2 years in patients with AS. The study consists of a 6-week screening period, a 12-week period (phase I: run-in phase) of treatment with golimumab for all subjects followed by a 96-week controlled treatment period (phase II: core phase) with golimumab plus celecoxib versus golimumab alone, and a safety follow-up period of 4 weeks. At week 108, the primary study endpoint radiographic spinal progression (as assessed by the change in the modified Stoke Ankylosing Spondylitis Spine Score after 2 years) will be evaluated. Ethics and dissemination The study will be performed according to the principles of good clinical practice and the German drug law. The written approval of the independent ethics committee and of the German federal authority have been obtained. On study completion, results are expected to be published in a peer- reviewed journal. Trial registration number ClinicalTrials.gov register (NCT02758782) and European Union Clinical Trials Register (EudraCT No 2016-000615-33)

Diagnostic accuracy of inflammatory back pain for axial spondyloarthritis in rheumatological care

Objective: Inflammatory back pain (IBP), the key symptom of axial spondyloarthritis (axSpA), including ankylosing spondylitis, has been proposed as a screening test for patients presenting with chronic back pain in primary care. The diagnostic accuracy of IBP in the rheumatology setting is unknown. Methods: Six rheumatology centres, representing secondary and tertiary rheumatology care, included routinely referred patients with consecutive chronic back pain with suspicion of axSpA. IBP (diagnostic test) was assessed in each centre by an independent (blinded) rheumatologist; a second (unblinded) rheumatologist made the diagnosis (axSpA or no-axSpA), which served as reference standard. Results: Of 461 routinely referred patients, 403 received a final diagnosis. IBP was present in 67.3%, and 44.6% (180/403) were diagnosed as axSpA. The sensitivity of IBP according to various definitions (global judgement, Calin, Berlin, Assessment of SpondyloArthritis international Society criteria for IBP) was 74.4%-81.1 % and comparable to published figures, whereas the specificity was unexpectedly low (25.1%-43.9%). The resulting positive likelihood ratios (LR+) were 1.1-1.4 and without major differences between sets of IBP criteria. The presence of IBP according to various definitions increased the probability of axSpA by 2.5%-8.4% only (from 44.6% to 47.1%-53.0%). Conclusions: The diagnostic utility of IBP in the rheumatology setting was smaller than expected. However, this was counterbalanced by a high prevalence of IBP among referred patients, demonstrating the effective usage of IBP in primary care as selection parameter for referral to rheumatology. Notably, this study illustrates potential shifts in specificity and LR+ of diagnostic tests if these tests are used to select patients for referral

Asymptomatic secondary hyperparathyroidism can mimic sacroiliitis on computed tomography

Secondary hyperparathyroidism (sHPT) as a result of chronic kidney disease (CKD) is a common health problem and has been reported to manifest at the sacroiliac joints (SIJ). The aim of this investigation was to systematically assess sacroiliac joint changes in asymptomatic sHPT as detected by high-resolution CT. Included in this IRB-approved retrospective case-control study were 56 patients with asymptomatic sHPT as well as 259 matched controls without SIJ disease. Demographic data were retrieved from electronic patient records. High-resolution computed tomography datasets of all patients were subjected to a structured scoring, including erosions, sclerosis, osteophytes, joint space alterations and intraarticular calcifications. Chi(2) tests were used to compare frequencies of lesions. Erosions were significantly more prevalent in patients with sHPT, and were found mainly in the ventral (28.6% vs. 13.9%; p = 0.016) and middle (17.9% vs. 7.7%; p = 0.040) iliac portions of the SIJ. Partial ankylosis was rare in both cohorts (3.6% vs. 5.0%; p > 0.999); complete ankylosis was not observed. Neither extent not prevalence of sclerosis or calcifications differed significantly between groups. Joint lesions reminiscent of sacroiliitis can be found in a substantial portion of asymptomatic patients with secondary hyperparathyroidism. Further investigations into the clinical significance of these findings are warranted

Incorporation of the anteroposterior lumbar radiographs in the modified Stoke Ankylosing Spondylitis Spine Score improves detection of radiographic spinal progression in axial spondyloarthritis

Background: To evaluate the performance of the extended modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) incorporating information from anteroposterior (AP) lumbar radiographs as compared to the conventional mSASSS in detection of radiographic spinal progression in patients with axial spondyloarthritis (axSpA) Methods: A total of 210 patients with axSpA, 115 with radiographic axSpA (r-axSpA), and 95 with non-radiographic axSpA (nr-axSpA), from the GErman SPondyloarthritis Inception Cohort (GESPIC), were included in the analysis based on the availability of spinal radiographs (cervical spine lateral, lumbar spine lateral, and AP views), at baseline and year 2. Two trained readers independently scored lateral cervical and lumbar spine images according to the mSASSS system (0-3 per vertebral corner, 0-72 in total). In addition, all vertebral corners of vertebral bodies visible on lumbar AP radiographs (lower T12 to upper S1) were assessed according to the same scoring system that resulted in a total range for the extended mSASSS from 0 to 144. Reliability and sensitivity to detect radiographic spinal progression of the extended mSASSS as compared to the conventional mSASSS were evaluated. Results: The reliability of conventional and extended scores was excellent with intraclass correlation coefficients (ICCs) of 0.926 and 0.927 at baseline and 0.920 and 0.933 at year 2, respectively. The mean ± SD score for mSASSS and extended mSASSS at baseline were 4.25 ± 8.32 and 8.59 ± 17.96, respectively. The change score between baseline and year 2 was 0.73 ± 2.34 and 1.19 ± 3.73 for mSASSS and extended mSASSS, respectively. With the extended mSASSS, new syndesmophytes after 2 years were detected in 4 additional patients, new syndesmophytes or growth of existing syndesmophytes in 5 additional patients, and progression by ≥ 2 points in the total score in 14 additional patients meaning a 25%, 28%, and 46% increase in the proportion of patients with progression according to the respective definition as compared to the conventional score. Conclusions: Incorporation of lumbar AP radiographs in the assessment of structural damage in the spine resulted into detection of additional patients with radiographic spinal progression not captured by the conventional mSASSS score

Impact of age, sex, and joint form on degenerative lesions of the sacroiliac joints on CT in the normal population

Degeneration of the sacroiliac joints (SIJs) is a common finding, while its underlying cause and development remain incompletely understood. The aim of this investigation was to describe the spatial distribution of degenerative SIJ changes across age groups and to investigate for the first time their relationship to anatomical form and sex. For this IRB-approved investigation, demographic data of 818 patients without SIJ disease were retrieved from electronic patient records. High-resolution computed tomography (CT) datasets of all patients were analysed retrospectively for seven predefined age groups (ten-year increments, from75). A structured scoring system was applied to assess sclerosis, osteophytes, joint space alterations, and anatomical form. Chi-square tests were used to compare frequencies of degenerative lesions, and logistic regression analyses were performed to investigate associations between demographic data, anatomical form, and the presence of structural lesions. Sclerosis and osteophytes were common findings, with an overall prevalence of 45.7% and 46.8%, respectively. Female sex had an odds ratio (OR) of 0.15 (95% CI: 0.08-0.27) for the presence of ventral osteophytes and of 4.42 (95% CI: 2.77-7.04) for dorsal osteophytes. Atypical joint forms were significantly more prevalent in women with 62.1% vs. 14.1% in men (p<0.001). Accessory joints increased the likelihood of dorsal sclerosis (OR 2.735; 95% CI 1.376-5.436) while a typical joint form decreased its likelihood (OR 0.174; 95% CI 0.104-0.293). Sex and anatomical joint form have a major impact on the development of degenerative lesions of the SIJs and their spatial distribution

Management of Axial Disease in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations

Objective. Axial involvement in patients with psoriatic arthritis (PsA) is a common subset of this condition, but a unanimous definition has yet to be established. It has been defined by using different criteria, ranging from the presence of at least unilateral grade 2 sacroiliitis to those used for ankylosing spondylitis (AS), or simply the presence of inflammatory low back pain (IBP). Our aim was to identify and evaluate the efficacy of therapeutic interventions for treatment of axial disease in PsA.Methods. This systematic review is an update of the axial PsA (axPsA) domain of the treatment recommen-dations project by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).Results. The systematic review of the literature showed that new biologic and targeted synthetic dis-ease-modifying antirheumatic drug classes, namely interleukin (IL)-17A and Janus kinase inhibitors, could be considered for the treatment of axPsA. This would be in addition to previously recommended treatments such as nonsteroidal antiinflammatory drugs, physiotherapy, simple analgesia, and tumor necrosis factor inhibitors. Conflicting evidence still remains regarding the use of IL-12/23 and IL-23 inhibitors.Conclusion. Further studies are needed for a better understanding of the treatment of axPsA, as well as vali-dated outcome measures

Axial Spondyloarthritis: Patient-Reported Impact in Europe

This open access book provides an overview of the International Map of Axial Spondyloarthritis (IMAS) project -focusing on Europe-, a wide-ranging, multi-disciplinary collaboration between academic groups, Health Care Professionals (HCPs), patient organizations and Novartis. IMAS was conceived to improve knowledge of Axial Spondyloarthritis (axSpA) and raise awareness of its heavy burden globally. By asking more than 2,000 patients across Europe about the impact of axSpA on multiple aspects of their life, the full extent of this disease was investigated from a direct patient perspective. This allowed a unique understanding of how living with axSpA affects the daily lives and well-being of patients, and how this varies between European countries. Axial Spondyloarthritis: Patient-Reported Impact in Europe highlights opportunities for progressing quality patient care to be applied to health services globally. HCPs, policy makers and patients will find this book to be an indispensable resource for improving the understanding of this chronic condition, including patients’ clinical outcomes, the protection of those at risk of psychological distress, and the economic burden on patients and society

Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis : 5-year results from the phase III MEASURE 1 extension study

Objective: This study aimed to report end-of-study results on efficacy and safety of secukinumab 150 mg through 5 years in patients with ankylosing spondylitis (AS; MEASURE 1 extension trial (NCT01863732)). Methods: After the 2-year core trial, 274 patients receiving subcutaneous secukinumab 150 or 75 mg (following intravenous loading or initial placebo treatment to 16/24 weeks) every 4 weeks were invited to enter the 3-year extension study. Dose escalation from 75 to 150 mg (approved dose) was allowed at or after week 156 based on the judgement of the treating physician. Assessments at week 260 (5 years) included Assessment of SpondyloArthritis international Society (ASAS) 20/40 and other efficacy outcomes. Data are presented as observed. Safety assessment included all patients who received >= 1 dose of study treatment. Results: Of the 274 patients who entered the extension study, 84% (230/274) completed 5 years of treatment. ASAS20/40 responses were 78.6/65.2%, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response was 63.4% and mean (+/- SD) BASDAI total score was 2.6 +/- 1.76 with secukinumab 150 mg at 5 years. Improvements in efficacy outcomes were sustained through 5 years. A total of 82 patients on secukinumab 75 mg (56.2%) had their dose escalated to 150 mg after week 168; ASAS40, ASAS-PR, ASAS 5/6 and BASDAI50 responses were improved in patients whose dose was escalated from secukinumab 75 to 150 mg. Secukinumab was well tolerated with a safety profile consistent over the course of the study. Conclusions: Secukinumab 150 mg provided sustained efficacy across multiple domains of AS with a favourable and consistent safety profile through 5-year treatment. Over 50% of patients required dose escalation from 75 to 150 mg and efficacy improved in these patients

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

Objective: To 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). Methods: 137 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. Results: Baseline 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. Conclusion: Independent 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