Impact of patient characteristics on ASDAS disease activity state cut-offs in axial spondyloarthritis: results from nine European rheumatology registries.

OBJECTIVES: To re-evaluate cut-offs for disease activity states according to the Axial Spondyloarthritis Disease Activity Score (ASDAS), and study the impact of sex, age, calendar time, disease and symptom duration on ASDAS and ASDAS cut-offs in a large contemporary cohort. METHODS: Data from 2939 patients with axial spondyloarthritis (axSpA) starting their first tumour necrosis factor inhibitor in nine European registries were pooled and analysed. Receiver operating characteristic analyses were performed to identify cut-offs against external criteria. Six-month data including patient and physician global assessments, both ≤1 (0-10 integer scale), and Assessment of SpondyloArthritis International Society partial remission were used for separation of inactive disease (ID) from low disease activity (LDA), while patient and physician global ≤3 were applied as external criteria to separate LDA from high disease activity (HDA). Patient and physician global ≥6 were applied to separate HDA from very high disease activity in baseline data. RESULTS: The three ASDAS cut-offs identified to separate the four disease activity states in the overall patient population were <1.3, <2.0 and >3.5. Cut-offs for ID and LDA in women were higher (<1.5 and <2.0, respectively) than in men (<1.3 and <1.9), as were cut-offs in patients ≥45 years (<1.5 and <2.2) versus ≤34 years (<1.2 and <1.9) and 35-44 years (<1.3 and <1.8). Cut-offs were independent of calendar time and disease duration. CONCLUSIONS: Re-evaluation of ASDAS cut-offs for disease activity states in a large multi-national axSpA cohort resulted in cut-offs similar to those currently endorsed. Differences in cut-offs between sex and age groups for ID and LDA were observed, but the differences were minor.

Effect of apremilast on hand and whole-body MRI assessments of inflammation in patients with psoriatic arthritis (MOSAIC): a phase 4, multicentre, single-arm, open-label study.

BACKGROUND: The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE. METHODS: MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years or older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have at least three swollen and three tender joints with hand involvement and at least one active enthesitis site according to the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026). FINDINGS: Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Of these 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks of treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -2·32 (95% CI -4·73 to 0·09). 95 (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment-emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment-emergent adverse events were considered to be related to apremilast. INTERPRETATION: Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whole-body MRI, as an objective outcome measure in trials in patients with psoriatic arthritis. FUNDING: Amgen.

Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis.

OBJECTIVE: The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell-derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs) in RA. METHODS: Thirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4+ T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: HR-pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3+Th2 cells (r = -0.38, P = 0.04) and CXCR3+Th17 cells (r = -0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing. CONCLUSION: MTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA.

Clinical information on imaging referrals for suspected or known axial spondyloarthritis: recommendations from the Assessment of Spondyloarthritis International Society (ASAS).

OBJECTIVES: This study aims to establish expert consensus recommendations for clinical information on imaging requests in suspected/known axial spondyloarthritis (axSpA), focusing on enhancing diagnostic clarity and patient care through guidelines. MATERIALS AND METHODS: A specialised task force was formed, comprising 7 radiologists, 11 rheumatologists from the Assessment of Spondyloarthritis International Society (ASAS) and a patient representative. Using the Delphi method, two rounds of surveys were conducted among ASAS members. These surveys aimed to identify critical elements for imaging referrals and to refine these elements for practical application. The task force deliberated on the survey outcomes and proposed a set of recommendations, which were then presented to the ASAS community for a decisive vote. RESULTS: The collaborative effort resulted in a set of six detailed recommendations for clinicians involved in requesting imaging for patients with suspected or known axSpA. These recommendations cover crucial areas, including clinical features indicative of axSpA, clinical features, mechanical factors, past imaging data, potential contraindications for specific imaging modalities or contrast media and detailed reasons for the examination, including differential diagnoses. Garnering support from 73% of voting ASAS members, these recommendations represent a consensus on optimising imaging request protocols in axSpA. CONCLUSION: The ASAS recommendations offer comprehensive guidance for rheumatologists in requesting imaging for axSpA, aiming to standardise requesting practices. By improving the precision and relevance of imaging requests, these guidelines should enhance the clinical impact of radiology reports, facilitate accurate diagnosis and consequently improve the management of patients with axSpA.

Effect of Online Training on the Reliability of Assessing Sacroiliac Joint Radiographs in Axial Spondyloarthritis: A Randomized, Controlled Study.

OBJECTIVE: Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in the classification of axial spondyloarthritis but has moderate interreader agreement. We aimed to investigate the improvements of the reliability in scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone. METHODS: Nineteen readers, randomized to 2 groups (A or B), completed 3 calibration steps: (1) review of manuscripts, (2) review of slideshow and video with group A completing RETIC, and (3) re-review of slideshow and video with group B completing RETIC. The RETIC module gave instant feedback on readers' gradings and continued until predefined reliability (κ) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (exercises I to III). Agreement (κ) with an expert radiologist was assessed for mNY positivity/negativity and individual lesions. Improvements by training strategies were tested by linear mixed models. RESULTS: In exercises I, II, and III, mNY κ were 0.61, 0.76, and 0.84, respectively, in group A; and 0.70, 0.68, and 0.86, respectively, in group B (ie, increasing, mainly after RETIC completion). Improvements were observed for grading both mNY positivity/negativity and individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to the slideshow and video caused a significant κ increase of 0.17 (95% CI 0.07-0.27; P = 0.002) for mNY-positive and mNY-negative grading, whereas completion of the slideshow and video alone did not (κ = 0.00, 95% CI -0.10 to 0.10; P = 0.99). CONCLUSION: Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone.

Spine and Sacroiliac Joint Involvement in Newly Diagnosed Patients With Inflammatory Bowel Disease: Clinical and MRI Findings From a Population-Based Cohort.

INTRODUCTION: In patients with inflammatory bowel disease (IBD), co-occurring spondyloarthritis (SpA) leads to poorer outcomes and impaired quality of life, highlighting the importance of early detection and effective treatment. This is the first study to assess the prevalence and distribution of axial symptoms and magnetic resonance imaging (MRI)-detected involvement of the spine and sacroiliac joints (SIJs) in early IBD. METHODS: Newly diagnosed patients with IBD from a prospective, population-based cohort were consecutively recruited. Rheumatological interview, clinical, ultrasound, and MRI assessment for SIJ and spine inflammatory and structural lesions were made using validated scoring methods and consensus definitions of axial SpA (axSpA). RESULTS: Of 110 patients (ulcerative colitis: 70, Crohn's disease: 40, mean age of 42 years, and 40% male), 48 (44.9%) reported back and/or buttock pain, and 10 (9.1%) had inflammatory back pain. Seventeen (16.7%) patients had MRI findings indicative of axSpA; only 10 of these patients had axial symptoms. Inflammatory MRI lesions were present in SIJs and the spine of 27 (26.5%) and 30 (30.3%) patients, respectively. The Assessment of SpondyloArthritis International Society classification criteria for axSpA were met in 11 (10%) cases. MRI findings typical of axSpA were associated with peripheral joint and entheseal inflammation detected by ultrasound ( P = 0.04). No differences in clinical or imaging findings were found between patients with ulcerative colitis and Crohn's disease. DISCUSSION: One-in-6 newly diagnosed patients with IBD had MRI findings indicative of axSpA. As 40% of these patients were asymptomatic, this suggests that axSpA is underdiagnosed in early IBD. Multidisciplinary collaboration is essential to ensure early detection of axial inflammation and to enable optimal therapy preventing future structural damage and disability.

Spinal Lesions in Axial Psoriatic Disease: How Should They Be Identified and Quantified by Magnetic Resonance Imaging?

Proper assessment of patients with psoriatic arthritis (PsA) requires assessment of all disease domains, including axial disease. Magnetic resonance imaging (MRI) is the method of choice for evaluating axial involvement in PsA. When assessing patients with PsA for spinal involvement, it is important to assess both vertebral body lesions and posterolateral lesions, such as inflammation in facet joints and costovertebral joints, and enthesitis at spinous and transverse processes. The Canada-Denmark (CanDen) assessment system for spine MRIs is the preferred method for detailed evaluation of inflammation and structural damage at various anatomical locations in the spine, and it is reproducible and sensitive to change. The Assessment of Spondyloarthritis international Society (ASAS) has recently published MRI definitions of inflammatory and structural lesions in the spine, incorporating the CanDen definitions of spinal lesions on MRI. Applying the ASAS definitions and the CanDen assessment system in clinical practice and trials is recommended. Ongoing research/studies, not least the Axial Involvement in Psoriatic Arthritis (AXIS) study, may provide a data-driven definition of axial involvement in PsA. Ongoing research is expected to further improve and validate assessment tools for axial PsA and to provide a much-needed data-driven consensus-based definition of axial involvement in PsA.

Sex differences in patient-reported outcomes and the association with clinical factors in axial spondyloarthritis patients treated with tumour necrosis factor inhibitors.

OBJECTIVES: To investigate sex differences in patient-reported outcome measures (PROMs) among axSpA patients initiating their first TNFi and identify factors contributing to these disparities over the follow-up. METHODS: Data were included from 15 EuroSpA registries and consisted of axSpA patients initiating their first TNFi, with ≥2 measurements for each analysed PROM (BASDAI and BASFI, scale 0-100) taken at any time point. Linear mixed models were employed to analyse sex differences in PROMs over 24 months and to evaluate how baseline characteristics were related to the observed sex differences. RESULTS: We analysed 13 102 (38% women) in the BASDAI analyses and 10 623 (38% women) in the BASFI analyses. At follow-up, mean sex differences in BASDAI increased from 4.3 units at baseline (95% CI, 3.5-5.1)-8.0 (7.2-8.8) at 6 months, and in BASFI from 2.2 (1.4-3.1)-4.6 (3.6-5.5), with consistently worse scores in women. Baseline characteristics could not substantially account for the observed sex differences over time; however, the magnitude of the sex differences was reduced by HLA-B27 positivity, longer disease duration, and increased CRP levels, but increased by TNFi initiation in later years and peripheral arthritis. CONCLUSION: In axSpA patients initiating their first TNFi, baseline sex differences in BASDAI and BASFI increased two-fold after 6 months of treatment and persisted thereafter, with worse scores in women. Several baseline characteristics moderated the sex differences, though none could fully account for them. These findings improve our understanding of sex differences and underscore their importance in axSpA.

Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.

OBJECTIVES: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT). METHODS: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking. RESULTS: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks. CONCLUSIONS: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice. TRIAL REGISTRATION NUMBER: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.

Effectiveness of secukinumab in radiographic and non-radiographic axial spondyloarthritis: a European routine-care observational study.

OBJECTIVES: To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe. METHODS: Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0-10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.3 after 6/12/24 months of secukinumab treatment were calculated.Remission and drug retention rates in r-axSpA versus nr-axSpA patients were compared by logistic and Cox regression models (unadjusted/adjusted for age+sex/adjusted for multiple confounders). RESULTS: Overall, 1161 secukinumab-treated patients were included (r-axSpA/nr-axSpA: 922/239). At baseline, r-axSpA patients had longer disease duration and higher C reactive protein, were more often male and HLA-B27 positive and had received fewer prior biological or targeted synthetic disease-modifying antirheumatic drugs compared with nr-axSpA patients, whereas PROs were largely similar.During follow-up, crude PRO remission rates were significantly higher in r-axSpA compared with nr-axSpA patients (6 months: pain≤2: 40%/28%, OR=1.7; BASDAI≤2: 37%/25%, OR=1.8), as were drug retention rates (24 months: 66%/58%, HR 0.73 (ref: r-axSpA)). Proportions of patients achieving ASDAS ID were low for both groups, particularly nr-axSpA (6 months: 11%/8%).However, when adjusting for age+sex, these differences diminished, and after adjusting for multiple confounders, no significant between-group differences remained for either remission or drug retention rates. CONCLUSION: Crude remission/drug retention rates in European secukinumab-treated patients were higher in r-axSpA compared with nr-axSpA patients. In adjusted analyses, secukinumab effectiveness was similar in both groups, suggesting that observed differences were related to factors other than radiographic status.

Evidence for routine brain-to-pelvis imaging and antiplatelet therapy in patients diagnosed with fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a disease of the musculature of arterial walls leading to stenoses, aneurysms, and dissections. The purpose of this report was to summarize the evidence for (1) one-time routine imaging from brain-to-pelvis and (2) lifelong antiplatelet therapy, for example, aspirin, for patients diagnosed with FMD as suggested by an international consensus report from 2019. PubMed was systematically searched, and the evidence providing a basis for the current consensus points, as well as articles published since, were reviewed. In four registries evaluating patients with FMD, the prevalence of multivessel involvement, aneurysms, and dissections was reported to be 43.5%-66.3%, 21.6%-30.6%, and 5.6%-28.1%, respectively. Any antiplatelet drug was used in 72.9% of patients, and aspirin was prescribed in up to 70.2% of patients. Based on the high prevalence of vascular manifestations, their associated morbidity, and the potential for endovascular or surgical intervention, the suggestion of one-time brain-to-pelvis screening with computed tomography angiography or magnetic resonance angiography is well supported. Contrarily, the evidence to support the consensus statement of lifelong antiplatelet therapy to all patients in the absence of contraindications is more uncertain since a beneficial effect has not been demonstrated specifically in patients with fibromuscular dysplasia. Therefore, until the efficacy and safety of primary thromboprophylaxis have been demonstrated in this patient group specifically, it may be equally appropriate to only use antiplatelet agents in patients with a clear indication after individual evaluation according to risk factors for thrombotic and thromboembolic complications.

Comparing DAPSA, DAPSA28, and DAS28-CRP in Patients With Psoriatic Arthritis Initiating a First Tumor Necrosis Factor Inhibitor Across Nine European Countries.

OBJECTIVE: Because 66/68 joint counts are not always performed in routine care, we aimed to determine which of the modified 28-joint disease activity index for psoriatic arthritis (DAPSA28) or 28-joint disease activity score with C-reactive protein (DAS28-CRP) should be preferred for monitoring disease activity in psoriatic arthritis (PsA) when the original DAPSA (66/68 joints) is not available. METHODS: Prospectively collected real-world data of European bionaive patients with PsA initiating a first tumor necrosis factor inhibitor were pooled. Remission and response status were evaluated at 6 months by remission (DAPSA ≤ 4, DAPSA28 ≤ 4, and DAS28-CRP < 2.6), response (75% improvement for DAPSA and DAPSA28), and combined EULAR good/moderate responses for DAS28-CRP. Logistic regression analyses on multiple imputed data were used to identify baseline predictors. RESULTS: Remission and response cohorts included 3,159 and 1,866 patients, respectively. The 6-month proportions achieving remission/response were DAPSA (27%/44%), DAPSA28 (28%/44%), and DAS28-CRP (59%/80%). Of 14 possible baseline predictors, 11 predicted both DAPSA and DAPSA28 remission (8 of which also predicted their response, indicated by "*"): longer disease duration*, male sex*, and higher CRP* were positive, whereas older age*, higher body mass index*, patient fatigue*, and global, physician global, health assessment questionnaire score*, and tender and swollen* joint counts were negative predictors. Eight and five of these predicted DAS28-CRP remission and response, respectively. CONCLUSION: In patients with PsA, DAPSA28 should be preferred over DAS28-CRP as a substitute for DAPSA when 66/68 joint counts are not available because of the large overlap in remission and response status and in predictors between DAPSA and DAPSA28.

Reporting Sacroiliac Joint Imaging Performed for Known or Suspected Axial Spondyloarthritis: Assessment of SpondyloArthritis International Society Recommendations.

Whereas previous projects attempted to standardize imaging in patients with axial spondyloarthritis (axSpA), few studies have been published about the need for specific details regarding the image acquisition and lesions that may be less familiar to general radiologists. This work reports consensus recommendations developed by the Assessment of SpondyloArthritis International Society (ASAS) that aim to standardize the imaging reports in patients suspected of having or with known axSpA. A task force consisting of radiologists and rheumatologists from ASAS and one patient representative formulated two surveys that were completed by ASAS members. The results of these surveys led to the development of 10 recommendations that were endorsed by 73% (43 of 59) of ASAS members. The recommendations are targeted to the radiologist and include best practices for the inclusion of clinical information, technical details, image quality, and imaging findings in radiology reports. These recommendations also emphasize that imaging findings that indicate differential diagnoses and referral suggestions should be included in the concluding section of the radiology report. With these recommendations, ASAS aims to improve the diagnostic process and care for patients suspected of having or with known axSpA.

Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: a NORD-STAR study.

OBJECTIVE: This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA). METHODS: This report included 793 participants with untreated early RA from the randomised, longitudinal NORD-STAR trial, all of whom had their body mass index (BMI) assessed at baseline. Obesity was defined as BMI ≥30 kg/m2. All participants were randomised 1:1:1:1 to one of four treatment arms: active conventional treatment, certolizumab-pegol, abatacept and tocilizumab. Clinical and laboratory measurements were performed at baseline and at 8, 12, 24 and 48-week follow-up. The primary endpoint for this report was response to treatment based on Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) remission and Disease Activity Score with 28 joints using C-reactive protein (DAS28-CRP) <2.6 stratified by BMI. RESULTS: Out of 793 people included in the present report, 161 (20%) had obesity at baseline. During follow-up, participants with baseline obesity had higher disease activity compared with those with lower BMI, despite having similar disease activity at baseline. In survival analyses, obesity was associated with a lower likelihood of achieving response to treatment during follow-up for up to 48 weeks (CDAI remission, HR 0.84, 95% CI 0.67 to 1.05; SDAI, HR 0.77, 95% CI 0.62 to 0.97; DAS28-CRP <2.6, HR 0.78, 95% CI 0.64 to 0.95). The effect of obesity on response to treatment was not influenced by the treatment arms. CONCLUSION: In people with untreated early RA followed up for up to 48 weeks, obesity was associated with a lower likelihood of good treatment response, irrespective of the type of randomised treatment received. TRIAL REGISTRATION NUMBER: NCT01491815.

Cut-Offs for Disease Activity States in Axial Spondyloarthritis With Ankylosing Spondylitis Disease Activity Score (ASDAS) Based on C-Reactive Protein and ASDAS Based on Erythrocyte Sedimentation Rate: Are They Interchangeable?

OBJECTIVE: Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. METHODS: We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. RESULTS: In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. CONCLUSION: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

Adding ultrasound to treat-to-target shows no benefit in achieving clinical remission nor in slowing radiographic progression in rheumatoid arthritis: results from a multicenter prospective cohort.

OBJECTIVE: To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA. METHODS: Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3 months and hands and feet radiographs every 6 months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed. RESULTS: A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [ß(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12 months later. CONCLUSION: Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit.

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.

OBJECTIVE: Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was to compare 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Drug effectiveness of 2nd and 3rd TNF inhibitors in psoriatic arthritis - relationship with the reason for withdrawal from the previous treatment.

OBJECTIVE: To investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment. METHODS: Prospectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively). RESULTS: We included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67-70%) and 66% (64-68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi. CONCLUSION: Two-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE.

Detection of structural lesions of the sacroiliac joints in patients with spondyloarthritis: A comparison of T1-weighted 3D spoiled gradient echo MRI and MRI-based synthetic CT versus T1-weighted turbo spin echo MRI.

OBJECTIVES: To investigate the detection of erosion, sclerosis and ankylosis using 1 mm 3D T1-weighted spoiled gradient echo (T1w-GRE) MRI and 1 mm MRI-based synthetic CT (sCT), compared with conventional 4 mm T1w-TSE. MATERIALS AND METHODS: Prospective, cross-sectional study. Semi-coronal 4 mm T1w-TSE and axial T1w-GRE with 1.6 mm slice thickness and 0.8 mm spacing between overlapping slices were performed. The T1w-GRE images were processed into sCT images using a commercial deep learning algorithm, BoneMRI. Both were reconstructed into 1 mm semi-coronal images. T1w-TSE, T1w-GRE and sCT images were assessed independently by 3 expert and 4 non-expert readers for erosion, sclerosis and ankylosis. Cohen's kappa for inter-reader agreement, exact McNemar test for lesion frequencies and Wilcoxon signed-rank test for confidence in lesion detection were used. RESULTS: Nineteen patients with axial spondyloarthritis were evaluated. T1w-GRE increased inter-reader agreement for detecting erosion (kappa 0.42 vs 0.21 in non-experts), increased detection of erosion (57 vs 43 of 152 joint quadrants) and sclerosis (26 vs 17 of 152 joint quadrants) among experts, and increased reader confidence for scoring erosion and sclerosis. sCT increased inter-reader agreement for detecting sclerosis (kappa 0.69 vs 0.37 in experts) and ankylosis (0.71 vs 0.52 in non-experts), increased detection of sclerosis (34 vs 17 of 152 joint quadrants) and ankylosis (20 vs 13 of 76 joint halves) among experts, and increased reader confidence for scoring erosion, sclerosis and ankylosis. CONCLUSION: T1w-GRE and sCT increase sensitivity and reader confidence for the detection of erosion, sclerosis and ankylosis, compared with T1w-TSE. CLINICAL RELEVANCE STATEMENT: These methods improve the detection of sacroiliac joint structural lesions and might be a useful addition to SIJ MRI protocols both in routine clinical care and as structural outcome measures in clinical trials.