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Axial spondyloarthritis (axSpA) encompasses both radiographic and non-radiographic axSpA. It is a chronic inflammatory disease with a predilection for involving the axial skeleton. The most common presenting symptoms are chronic back pain and spinal stiffness but peripheral and extra-musculoskeletal manifestations occur also frequently. The diagnosis of axSpA relies on the recognition of a clinical pattern of the disease, based on clinical, laboratory and imaging features. The Assessment in SpondyloArthritis international Society classification criteria for axSpA are valid and well implemented for research purposes. Sustained disease activity, measured by validated tools such as the Ankylosing Spondylitis Disease Activity Score, leads to irreversible structural damage and poor functioning and therefore should be abrogated. As part of the management algorithm, non-steroidal anti-inflammatory drugs remain as the first line of pharmacological treatment besides physiotherapy. As a second line, tumour necrosis factor inhibitor and interleukin-17 inhibitor are available but recently Janus kinase inhibitors have also shown efficacy in improving symptoms of the disease.

ObjectiveTo investigate complement system activation and complement protein levels in relation to radiographic progression in axial spondyloarthritis (axSpA) within a longitudinal randomised controlled trial (RCT) of radiographic axSpA patients initiating tumour necrosis factor inhibitor (TNFi) therapy.MethodsSerum samples from 96 patients with active radiographic axSpA in the multicentre RCT CONSUL were analysed by immunoassays for complement activation, that is, C3dg and complement proteins (MBL, CL-L1, M-, H- and L-ficolin; MASP-1,–2 and −3; and MAp44) before and after 108 weeks of TNF inhibitor therapy with golimumab.ResultsBaseline serum levels of total complement activation, that is, C3dg and lectin pathway activating protease MASP-1 were elevated in patients with new bone formation (new syndesmophytes and/or growth of existing syndesmophytes) after 2 years of follow-up, whereas baseline MASP-3 levels were decreased. Assessed by univariate logistic regression, baseline levels of MASP-1, MASP-3 and C3dg were associated with the development of new bone formation and remained significant in a corresponding multivariate logistic regression analysis. At follow-up, serum levels of C3dg and complement lectin pathway initiator L-ficolin were elevated in patients with new bone formation, and C3dg remained significant in a corresponding multivariate logistic regression analysis.ConclusionsComplement activation marker C3dg, MASP-1 and MASP-3 levels before TNFi therapy predicted new bone formation after 2 years of follow-up among axSpA patients with a high risk of radiographic progression. Furthermore, levels of L-ficolin and C3dg at follow-up were elevated in axSpA patients with new bone formation. Our findings support an association between activation of the complement system and radiographic spinal progression in patients with axSpA.

BackgroundA 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.MethodsBaseline 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.ResultsAcross 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.ConclusionThis 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 numberNCT02505542.

ObjectiveTo assess the long-term effect of bimekizumab, a dual inhibitor of IL-17A and IL-17F, on patient-reported symptoms, function and health-related quality of life (HRQoL) in patients with axial spondyloarthritis (axSpA) from phase 3 studies and their open-label extension.MethodsBE MOBILE 1 (non-radiographic-axSpA) and 2 (radiographic-axSpA) comprised 16-week double-blind placebo-controlled and 36-week maintenance periods. From week 16, all patients received subcutaneous bimekizumab 160 mg every 4 weeks. At week 52, eligible patients could enrol in the open-label extension BE MOVING and continue bimekizumab treatment. Spinal pain (rated on a numerical rating scale from 0 (no pain) to 10 (maximum pain)), morning stiffness (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) average of Q5/6), fatigue (BASDAI Q1; Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale), sleep quality (Medical Outcomes Study (MOS) Sleep Scale Index II), physical function (Bath Ankylosing Spondylitis Functional Index (BASFI)) and HRQoL (36-Item Short Form Survey (SF-36) physical component summary (PCS)/mental component summary (MCS); Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire) were reported to week 104.ResultsIn total, 494/586 (84.3%) patients entered BE MOVING at week 52; 456 completed week 104. Patients reported substantial changes from baseline to week 104 in total spinal pain (−4.3), nocturnal spinal pain (−4.3), morning stiffness (−4.3) and fatigue (BASDAI Q1: −3.4; FACIT-Fatigue: +9.9). Over half reported total and nocturnal spinal pain scores ≤3 at week 104. Similar improvements to week 104 were shown in sleep (MOS-Sleep Scale: +10.2), physical function (BASFI: −2.9) and HRQoL (SF-36 PCS: +12.4; ASQoL: −5.6).ConclusionsBimekizumab treatment resulted in sustained improvements in patient-reported symptoms and their impacts across the full disease spectrum of axSpA over 2 years, underscoring its long-term potential for improving patients’ daily lives.Trial registration numbers NCT03928704, NCT03928743, NCT04436640

IntroductionThis 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).MethodsWe 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.Results136 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.ConclusionThere 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 numberNCT01087762.

ObjectivesEarly disease activity control with targeted therapies may improve long-term outcomes in axial spondyloarthritis (axSpA). Here, we evaluated the efficacy of upadacitinib in patients with axSpA with shorter versus longer symptom durations.MethodsSELECT-AXIS 1 and 2 studies enrolled patients with radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) naïve to biologic disease-modifying antirheumatic drugs (bDMARD-naïve) and with an intolerance or inadequate response to bDMARD therapy. Patients were stratified by symptom duration (nr-axSpA: early vs established (≤2 vs >2 years=Assessment of SpondyloArthritis international Society (ASAS) definition) and shorter vs longer (≤5 vs >5 years); r-axSpA: ≤5 vs >5 years). Efficacy endpoints assessed through week 14 included the proportion of patients achieving Axial Spondyloarthritis Disease Activity Score and ASAS40 responses, among others. Across all endpoints, the efficacy of upadacitinib versus placebo was assessed by relative risk (RR), and the placebo-adjusted effect of upadacitinib between shorter versus longer symptom duration was assessed by the RR ratio.ResultsAt week 14, better responses were observed in patients treated with upadacitinib in all endpoints assessed compared with placebo, regardless of symptom duration. When comparing patients with early/shorter versus established/longer symptom durations, for all measures assessed, no statistically significant differences were observed except for the change from baseline in high-sensitivity C-reactive protein in the nr-axSpA group, with a better response in early disease (difference –8.2, 95% CI –14.9 to –1.6).ConclusionRegarding short-term outcomes, both subgroups of patients (shorter axSpA symptom duration (≤2 years) and longer symptom duration (>2 years)) achieved comparable results when treated with upadacitinib.Trial registration numberNCT03178487 (SELECT-AXIS 1) and NCT04169373 (SELECT-AXIS 2).

BackgroundBimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated 2-year efficacy in non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axSpA (r-axSpA) phase III studies.ObjectiveAssess the impact of BKZ on peripheral manifestations to week 104 of those studies.MethodsBE MOBILE 1 (nr-axSpA) and 2 (r-axSpA) each comprised a 16-week double-blind, placebo-controlled period, then all received BKZ 160 mg every 4 weeks for 36 weeks. Patients not meeting withdrawal criteria could enter a combined open-label extension. We report change in enthesitis (Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)) in patients with baseline MASES>0, peripheral arthritis (swollen joint count (SJC)/Disease Activity Index for Psoriatic Arthritis (DAPSA)) in patients with baseline SJC>0 and proportions achieving DAPSA disease states to week 104. Resolution of enthesitis (MASES=0)/arthritis (SJC=0) is reported to week 104 for those with baseline enthesitis/arthritis. We also report associations between peripheral manifestation resolution (MASES=0/SJC=0) and week 104 clinical outcomes in those with baseline enthesitis/arthritis.ResultsAt baseline, 186/254 (73.2%) and 88/254 (34.6%) patients with nr-axSpA had enthesitis (MASES>0) and arthritis (SJC>0), respectively, compared with 199/332 (59.9%) and 66/332 (19.9%) patients with r-axSpA. Pooled BKZ/placebo-randomised patients with enthesitis (nr-axSpA/r-axSpA) showed average MASES improvement from 4.8/4.3 (baseline) to 1.6/1.3 (week 52) and 1.6/1.0 (week 104). Pooled BKZ/placebo-randomised patients with arthritis showed average SJC improvement from 4.0/4.5 (baseline) to 1.2/0.7 (week 52) and 0.9/0.6 (week 104). Over 60% of patients achieved DAPSA low disease activity/remission by week 52. Over 40%/60% patients achieved resolution of enthesitis (MASES=0)/arthritis (SJC=0) at week 104; enthesitis resolution was associated with larger improvements in week 104 clinical outcomes for patients with r-axSpA.ConclusionBKZ resulted in sustained improvements in peripheral manifestations to 2 years across the full disease spectrum of axSpA.

ObjectivesIn this post-hoc analysis of ESTHER trial, we aimed to investigate the longitudinal relationship between inflammation on MRI and the achievement of inactive disease/low disease activity in patients with axial spondyloarthritis (axSpA) treated with long-term tumor necrosis factor (TNF) inhibitor etanercept.MethodsOf the 76 patients with active axSpA in the ESTHER trial, we included all patients treated with etanercept for at least 6 months for main analysis. All clinical and MRI data from 4.5 years of follow-up were used in the analysis. MRIs of the spine and sacroiliac (SI) joints were performed at baseline, week 24, week 48 and yearly thereafter and were evaluated for active inflammatory lesions according to the Berlin MRI score.ResultsLongitudinal analysis showed that higher SI joint osteitis score was associated with higher Axial Spondyloarthritis Disease Activity Score (ASDAS) at the same time point (β=0.08, 95% CI (0.05; 0.11)) and at the next time point 6 months later (β=0.05, 95% CI (0.02; 0.07)). Furthermore, resolution of osteitis in the SI joint (Berlin MRI osteitis score of ≤1) was associated with lower ASDAS at the next time point (β=−0.26, 95% CI (−0.42; −0.09)), higher odds of achieving ASDAS low disease activity (OR=5.61, 95% CI (1.06; 29.67)) and inactive disease status (OR=2.23, 95% CI (1.01; 4.94)) at the next time point.ConclusionsThe presence of inflammation on SI joints-MRI is associated with higher disease activity in axSpA. Resolution of inflammation on MRI is associated with better clinical outcomes in the long-term follow-up. Thus, achieving complete resolution of inflammation is favourable for meeting the treatment goals in axSpA.Trial registration numberNCT00844142.

Axial spondyloarthritis manifests as a chronic inflammatory disease primarily affecting the sacroiliac joints and spine. Although chronic back pain and spinal stiffness are typical initial symptoms, peripheral (ie, enthesitis, arthritis, and dactylitis) and extra-musculoskeletal (ie, uveitis, inflammatory bowel disease, and psoriasis) manifestations are also common. Timely and accurate diagnosis is challenging and relies on identifying a clinical pattern with a combination of clinical, laboratory (HLA-B27 positivity), and imaging findings (eg, structural damage on pelvic radiographs and bone marrow oedema on MRI of the sacroiliac joints). The Assessment in SpondyloArthritis international Society classification criteria for axial spondyloarthritis are widely used for research and have contributed to a better understanding of the gestalt of axial spondyloarthritis. Persistent disease activity, assessed mainly by the Axial Spondyloarthritis Disease Activity Score, leads to irreversible structural damage and functional impairment. Management involves non-pharmacological (eg, education, smoking cessation, exercise, physiotherapy) and pharmacological therapy. Non-steroidal anti-inflammatory drugs remain first line pharmacotherapy, while tumour necrosis factor, IL-17, and Janus kinase inhibitors are considered second-line therapies. Future advances are expected to increase disease awareness, facilitate early and accurate diagnosis, optimise disease management, and enhance overall quality of life in patients with axial spondyloarthritis.

ObjectivesTo develop a consensual definition for the term ‘early axial spondyloarthritis—axSpA’—and ‘early peripheral spondyloarthritis—pSpA’.MethodsThe ASAS (Assessment of SpondyloArthritis international Society-Spondyloarthritis EARly definition) steering committee convened an international working group (WG). Five consecutive steps were followed: (1) systematic literature review (SLR); (2) discussion of SLR results within the WG and ASAS community; (3) a three-round Delphi survey inviting all ASAS members to select the items that should be considered for the definition; (4) presentation of Delphi results to the WG and ASAS community and (5) ASAS voting and endorsement (2023 annual meeting).ResultsFollowing the SLR, consensus was to proceed with an expert-based definition for early axSpA (81% in favour) but not for pSpA (54% against). Importantly, early axSpA should be based on symptom duration taking solely axial symptoms into account. 151–164 ASAS members participated in the Delphi surveys. Consensus was achieved for considering the following items within early axSpA definition: duration of symptoms ≤2 years; axial symptoms defined as cervical/thoracic/back/buttock pain or morning stiffness; regardless of the presence/absence of radiographic damage. The WG agreed that in patients with a diagnosis of axSpA ‘early axSpA’ should be defined as a duration of ≤2 years of axial symptoms. Axial symptoms should include spinal/buttock pain or morning stiffness and should be considered by a rheumatologist as related to axSpA. The ASAS community endorsed this proposal (88% in favour).ConclusionsEarly axSpA has newly been defined, based on expert consensus. This ASAS definition should be adopted in research studies addressing early axSpA.