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Background A consensus definition for active sacroiliitis by MRI, mentioned in the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axSpA), was published in 2009 and included a qualitative and quantitative MRI cut-off component. In 2021, updates to the quantitative component were preliminarily proposed. This post hoc analysis of part A of the phase 3 open-label C-OPTIMISE study (NCT02505542) explores the differences by applying the 2009 and preliminary 2021 inflammatory cut-offs on clinical outcomes of axSpA patients treated with certolizumab pegol.Methods Baseline MRI scans were used to classify 657 patients as MRI+ or MRI– according to the quantitative components of the 2009 and preliminary 2021 MRI cut-offs for inflammatory lesions. Clinical outcomes, including ASAS ≥40% improvement (ASAS40), Ankylosing Spondylitis Disease Activity Score and Bath Ankylosing Spondylitis Disease Activity Index, were reported to week 48.Results Across all analysed outcomes, 2009 MRI+ and preliminary 2021 MRI+ subgroups showed similar results. Notably, clinical outcomes for the discordant group (2009 MRI+but preliminary 2021 MRI– group; 53/657 [8.1%]) were close to those seen in MRI– patients according to either 2009 or preliminary 2021 inflammatory cut-offs, and notably different from the totality of MRI+ subgroups.Conclusion This analysis suggests that the preliminary 2021 cut-offs for MRI inflammatory lesions may slightly increase the specificity of the quantitative part of the 2009 MRI inflammatory lesion definition. The effects of the updated MRI cut-offs need to be assessed on the basis of efficacy outcomes and with the inclusion of aspects of structural changes.Trial registration number NCT02505542.

Introduction This post hoc analysis evaluated the relationship between objective measures of inflammation and clinical outcomes following 12 weeks of certolizumab pegol (CZP) treatment in patients with active axial spondyloarthritis (axSpA).Methods We report the proportion of patients achieving ≥50% and ≥75% improvements in clinical composite outcome measures of disease activity (Axial Spondyloarthritis Disease Activity Score [ASDAS], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) and objective measures of inflammation (C reactive protein [CRP], Ankylosing Spondylitis spine MRI score [ASspiMRI-a] Berlin score and Spondyloarthritis Research Consortium of Canada [SPARCC] MRI Sacroiliac Joints [SIJ] score) following 12 weeks of CZP treatment. Data from two independent readers over four MRI reading campaigns were pooled using a mixed model with repeated measures for each variable.Results 136 patients (radiographic axSpA [r-axSpA]: 76; non-radiographic axSpA [nr-axSpA]: 60) were included. Following CZP treatment, CRP, ASspiMRI-a Berlin score and SPARCC SIJ score were reduced by ≥50% in most patients (CRP: 136/136 [100.0%]; Berlin: 73/136 [53.7%]; SPARCC SIJ: 71/136 [52.2%]), and often by ≥75%. Less than half of patients with r-axSpA and nr-axSpA showed ≥50% reduction in clinical responses (BASDAI: 64/136 [47.1%]; ASDAS: 66/136 [48.5%]). These results were also observed at the individual patient level; ≥50% improvements in MRI/CRP inflammatory measures did not translate into similar improvements in clinical responses for most patients.Conclusion There is a potential disconnect between objective measures of inflammation and clinical outcome responses in patients with axSpA. The use of only clinical response measures as trial endpoints may underestimate anti-inflammatory treatment effects.Trial registration number NCT01087762.

Objective There is a paucity of data on long-term clinical responses in patients with non-radiographic axial spondyloarthritis (nr-axSpA) based on their baseline objective signs of inflammation such as MRI or C-reactive protein (CRP) levels. This study reports clinical outcomes up to 3 years of the C-axSpAnd trial, including safety follow-up extension (SFE) from Weeks 52 to 156, stratified by patients’ baseline MRI and CRP status.Methods C-axSpAnd (NCT02552212) was a phase 3, multicentre study that evaluated certolizumab pegol (CZP) in patients with active nr-axSpA who had active sacroiliitis on MRI and/or elevated CRP. In this post hoc analysis, efficacy outcomes are reported to Week 156 of C-axSpAnd for patients stratified according to their MRI and CRP status at Week 0 (MRI+/CRP−, MRI−/CRP+ and MRI+/CRP+).Results Across all outcome measures, including major improvement in Ankylosing Spondylitis Disease Activity Score (ASDAS-MI) and Assessment of SpondyloArthritis international Society criteria ≥40% response (ASAS40), outcomes were generally sustained in SFE patients from Week 52 to Week 156. MRI+/CRP+ patients showed numerically higher or comparable responses relative to MRI−/CRP+ and MRI+/CRP− patients at Weeks 52 and 156; however, all three subgroups demonstrated substantial improvements from Week 0 (in CZP-randomised patients, ASDAS-MI at Week 156 [observed case]: MRI+/CRP+: 73.1%, MRI–/CRP+: 52.2%, MRI+/CRP–: 30.4%; ASAS40: MRI+/CRP+: 76.9%, MRI–/CRP+: 62.5%, MRI+/CRP–: 65.2%).Conclusions In patients with nr-axSpA and objective signs of inflammation, long-term clinical outcomes achieved after 1 year were generally sustained at 3 years across MRI+/CRP+, MRI−/CRP+ and MRI+/CRP− subgroups.

Objective Tumor necrosis factor inhibitors (TNFi) are an effective treatment for non‐radiographic axial spondyloarthritis (nr‐axSpA). To be eligible, however, many authorities require patients with nr‐axSpA to show active sacroiliitis on magnetic resonance imaging (MRI) and/or an elevated C‐reactive protein (CRP) level, possibly resulting in a perception that patients with nr‐axSpA without both factors have only low responses to TNFi treatment. We evaluated clinical responses to certolizumab pegol (CZP) in patients with nr‐axSpA stratified by baseline MRI/CRP status. Methods C‐axSpAnd was a phase 3, multicenter study on CZP in adult patients with active nr‐axSpA and objective signs of inflammation. This analysis assessed efficacy of CZP over the 52‐week randomized, double‐blind, placebo‐controlled period in patients stratified into subgroups based on the presence of active sacroiliitis on MRI and CRP level at baseline. Results CZP‐treated patients across all MRI/CRP subgroups achieved clinical responses greater than placebo. Across outcome measures, CZP‐treated MRI+/CRP+ patients demonstrated the greatest clinical responses, but substantial improvements were also observed in CZP‐treated MRI+/CRP− and MRI−/CRP+ patients. Ankylosing Spondylitis Disease Activity Score Major Improvement response rates at week 52 among CZP‐treated patients (75.6% MRI+/CRP+; 47.5% MRI−/CRP+; and 29.7% MRI+/CRP−) were higher than rates in placebo groups (range: 3.9%‐12.5%). Assessment of SpondyloArthritis international Society 40% response, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondyloarthritis Functional Index had similar response patterns, although differences between the CZP‐treated MRI/CRP subgroups were smaller. Clinical responses among CZP‐treated patients were also observed in additional subgroups, including those with low Spondyloarthritis Research Consortium of Canada MRI sacroiliac joint inflammation scores and those with normal baseline CRP levels. Conclusion Our findings indicate that CZP treatment benefits patients with nr‐axSpA across MRI+/CRP+, MRI−/CRP+, and MRI+/CRP− subgroups.

Abstract Background Identification of predictive clinical factors of long-term treatment response may contribute to improved management of non-radiographic axSpA (nr-axSpA) patients. This analysis aims to identify whether any baseline characteristics or Week 12 clinical outcomes in nr-axSpA patients with elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) enrolled in the C-axSpAnd study are predictive of achieving clinical response after 1 year of certolizumab pegol (CZP). Methods C-axSpAnd (NCT02552212) was a phase 3, multicentre study, including a 52-Week double-blind, placebo-controlled period. Enrolled patients were randomised to CZP 200 mg Q2W or placebo. Predictors of Week 12 (CZP group only) and Week 52 clinical response were identified using a multivariate stepwise logistic regression analysis. Response variables included Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI), Assessment of SpondyloArthritis International Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index 50% response (BASDAI50) and ASDAS inactive disease (ASDAS-ID). Predictive factors assessed included demographic and baseline characteristics and clinical outcomes at Week 12. A p-value

Abstract Introduction Achievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP. Methods C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA,

With the widespread use of IoT applications and the increasing trend in the number of connected smart devices, the concept of routing has become very challenging. In this regard, the IPv6 Routing Protocol for Low-power and Lossy Networks (PRL) was standardized to be adopted in IoT networks. Nevertheless, while mobile IoT domains have gained significant popularity in recent years, since RPL was fundamentally designed for stationary IoT applications, it could not well adjust with the dynamic fluctuations in mobile applications. While there have been a number of studies on tuning RPL for mobile IoT applications, but still there is a high demand for more efforts to reach a standard version of this protocol for such applications. Accordingly, in this survey, we try to conduct a precise and comprehensive experimental study on the impact of various mobility models on the performance of a mobility-aware RPL to help this process. In this regard, a complete and scrutinized survey of the mobility models has been presented to be able to fairly justify and compare the outcome results. A significant set of evaluations has been conducted via precise IoT simulation tools to monitor and compare the performance of the network and its IoT devices in mobile RPL-based IoT applications under the presence of different mobility models from different perspectives including power consumption, reliability, latency, and control packet overhead. This will pave the way for researchers in both academia and industry to be able to compare the impact of various mobility models on the functionality of RPL, and consequently to design and implement application-specific and even a standard version of this protocol, which is capable of being employed in mobile IoT applications.

Introduction: Acute anterior uveitis (AAU), affecting up to 40% of patients with axial spondyloarthritis (axSpA), risks permanent visual deficits if not adequately treated. We report 2-year results from C-VIEW, the first study to prospectively investigate certolizumab pegol (CZP) on AAU in patients with active axSpA at high risk of recurrent AAU. Patients and methods: C-VIEW (NCT03020992) was a 104-week (96 weeks plus 8-week safety follow-up), open-label, multicenter study. Eligible patients had active axSpA, human leukocyte antigen-B27 (HLA-B27) positivity and a history of recurrent AAU (⩾2 AAU flares in total; ⩾1 in the year prior to baseline). Patients received CZP 400 mg at weeks 0, 2 and 4, then 200 mg every 2 weeks to week 96. The primary efficacy endpoint was the AAU flare event rate during 96 weeks’ CZP versus 2 years pre-baseline. Results: Of 115 enrolled patients, 89 initiated CZP (male: 63%; radiographic/non-radiographic axSpA: 85%/15%; mean disease duration: 9.1 years); 83 completed week 96. There was a significant 82% reduction in AAU flare event rate during CZP versus pre-baseline [rate ratio (95% confidence interval): 0.18 (0.12–0.28), p

Background Acute anterior uveitis (AAU) is the most common extra-articular manifestation in patients with axial spondyloarthritis (axSpA). C-VIEW investigates the impact of the Fc-free TNF inhibitor certolizumab pegol (CZP) on AAU flares in patients with active axSpA at high risk of recurrent AAU.Methods C-VIEW (NCT03020992) is a 96-week ongoing, multicentre, open-label, phase 4 study. Included patients had an axSpA diagnosis, a history of recurrent AAU (≥2 AAU flares, ≥1 flare in the year prior to study entry), HLA-B27 positivity, active disease, and failure of ≥2 non-steroidal anti-inflammatory drugs. Patients received CZP 400 mg at Weeks 0/2/4, then 200 mg every 2 weeks up to 96 weeks. This 48-week pre-planned interim analysis compares AAU flare incidence in the 48 weeks before and after initiation of CZP treatment, using Poisson regression to account for possible within-patient correlations.Results In total, 89 patients were included (male: 63%; radiographic/non-radiographic axSpA: 85%/15%; mean axSpA disease duration: 8.6 years). During 48 weeks’ CZP treatment, 13 (15%) patients experienced 15 AAU flares, representing an 87% reduction in AAU incidence rate (146.6 per 100 patient-years (PY) in the 48 weeks pre-baseline to 18.7 per 100 PY during CZP treatment). Poisson regression analysis showed that the incidence rate of AAU per patient reduced from 1.5 to 0.2 (p