Long-term clinical outcomes of certolizumab pegol treatment in non-radiographic axial spondyloarthritis stratified by baseline MRI and CRP status.

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.

The cost-effectiveness of a bimekizumab versus IL-17A inhibitors treatment-pathway in patients with active axial spondyloarthritis in Scotland.

OBJECTIVE: To estimate the cost-effectiveness of a treatment-pathway initiated with bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with axial spondyloarthritis (axSpA) compared with IL-17Ai's, ixekizumab, and secukinumab, from the NHS Scotland perspective. METHODS: The axSpA treatment-pathway was modeled using a decision tree followed by a lifetime Markov model. The pathway included first- and second-line biologic disease-modifying antirheumatic drugs (bDMARD), followed by best supportive care (bDMARD, nonbiologic). Bimekizumab followed by any bDMARD ("BKZ") was compared with IL-17Ai's: secukinumab 150 mg followed by a blend ("SEC") of dose up-titration to secukinumab 300 mg and any bDMARD, or ixekizumab followed by any bDMARD ("IXE"). Transition to the next therapy was triggered by Bath Ankylosing Spondylitis Disease Activity Index-50% (BASDAI50) non-response or any-cause discontinuation. A published network meta-analysis provided efficacy data. EuroQoL-5-dimensions utilities were derived by mapping from Ankylosing Spondylitis Disease Activity Score. Costs included disease management (linked to functional limitations), biologics acquisition (list prices), administration and monitoring (NHS 2021/22). Discounting was 3.5%/year. Probabilistic results from patients with non-radiographic axSpA and ankylosing spondylitis were averaged to reflect the axSpA disease spectrum. Scenario and sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) of BKZ was £24,801/quality-adjusted life-year (QALY) vs. SEC (95% credible interval £24,163-£25,895). BKZ had similar costs (Δ -£385 [-£15,239-£14,468]) and QALYs (Δ 0.039 [-0.748-0.825]) to IXE, with £1,523 (£862-£2,222) net monetary benefit. Conclusions remained unchanged in most scenarios. Results' drivers included BASDAI50 response rate and disease management cost. LIMITATIONS: Results were based on list prices. Data concerning up-titration to secukinumab 300 mg was scarce. CONCLUSIONS: The bimekizumab treatment-pathway represents a cost-effective option across the axSpA disease spectrum in Scotland. Bimekizumab is cost-effective compared to a secukinumab-pathway that includes dose up-titration, and has similar costs and QALYs to an ixekizumab-pathway.

Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy.

BACKGROUND: We aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi). METHODS: Using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA. RESULTS: This study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (𝛽 = 0.343, p = 0.011), whereas ASDAS was not (𝛽 = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200-2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678-1.455), after adjusting for other baseline characteristics. CONCLUSIONS: The changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.

Early identification of golimumab-treated patients with higher likelihood of long-term retention.

Background: The early identification of patients' profiles most likely to respond to and maintain long-term therapy with a biological drug can have clinical and cost-effectiveness implications. Objectives: To evaluate the utility of an innovative approach for early identification of patient profiles associated with long-term persistence of golimumab, a tumour necrosis factor inhibitor, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) under real-world conditions. Design: Retrospective non-interventional database analysis. Methods: Kaplan-Meier curves of golimumab retention over 8 years from the BIOBADASER registry, overall and by indication, were analysed using a novel approach (a two-phase decay model) to identify the point at which the golimumab retention curve shifted from rapid (indicating high golimumab discontinuation rate) to slow decay (low discontinuation rate). Factors associated with golimumab retention at these time points were identified using Cox regression, and retention rates for different patient profiles were calculated. Results: 885 patients were included. The golimumab retention curve shifted from rapid to slow decay at month 10 for the overall population (retention rate: 73.4%), at month 24 for RA patients (retention: 45.0%), and at month 8 for SpA, including axial SpA and PsA (81.6%). Factors associated with golimumab discontinuation at these early points were, overall, similar to those previously identified at year 8 (RA diagnosis, golimumab as second- or third-line of biological therapy, disease activity over the median and treatment with corticosteroids at golimumab initiation, advanced age [in RA], and female gender [in SpA]). Conclusion: With this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab.

Year in Review in Axial Spondyloarthritis Clinical Research and Guidelines: SPARTAN 2023 Annual Meeting Proceedings.

PURPOSE OF REVIEW: To highlight high impact clinical publications in spondyloarthritis from May 2022 to April 2023 that were summarized and presented at the SPARTAN annual meeting in May 2023. RECENT FINDINGS: Publications included updated guidelines on management of axial spondyloarthritis (axSpA) by ASAS-EULAR and development of a modified Juvenile Spondyloarthritis Disease Activity Index (JSpADA). Definitions were published for MRI lesions of the spine in axSpA and active and structural sacroiliac (SI) joint lesions in juvenile spondyloarthritis (JSpA). Anatomic variants of the sacroiliac joint were commonly detected using synthetic CT derived from pelvis MRI images. Anti-CD74 antibodies hold promise as a diagnostic biomarker for axSpA; however, the mechanism of such antibody development seems unrelated to gastrointestinal inflammation. High impact clinical publications in spondyloarthritis addressed lab-based and imaging biomarkers, outcome measures, and updated management guidelines.

Erosions on T1-Weighted Magnetic Resonance Imaging Versus Radiography of Sacroiliac Joints in Recent-Onset Axial Spondyloarthritis: 2-Year Data (EMBARK Trial and DESIR Cohort).

OBJECTIVE: (1) To compare the capacity to detect sacroiliac joint (SIJ) erosions and baseline-to-week 104 change in erosions between magnetic resonance imaging (MRI) and radiographs in recent-onset axial spondyloarthritis (axSpA); and (2) to compare treatment-discriminatory capacities of MRI and radiographic scores for erosion detection in patients receiving etanercept in the Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic axSpA (EMBARK) trial vs controls in the DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes) cohort. METHODS: Anonymized SIJ MRI and radiographs were assessed at patient and joint surface levels. Three readers evaluated MRI; 3 different readers evaluated radiographs. Final scores for comparison of radiographs and MRI for detection of erosions were assigned based on agreement of ≥ 2 of 3 readers' assessments. RESULTS: At baseline, discordance in erosion detection between imaging methods was more frequent for MRI erosions in the absence of radiographic erosions (48/224 [21.4%] patients) than for radiographic erosions in the absence of MRI erosions (14/224 [6.3%] patients; P < 0.001). After 104 weeks, a decrease in erosions was observed on MRI but not radiographs in 49/221 (22.2%) patients, and on radiographs but not MRI in 6/221 (2.7%) patients (P < 0.001). In the treatment-discriminant capacity analysis, the largest standardized differences between etanercept and control cohorts at week 104 were changes in Spondyloarthritis Research Consortium of Canada MRI erosion discrete score, changes in erosion average score, and meeting the modified New York criteria on radiographs, with unadjusted/adjusted Hedges G effect sizes of 0.40/0.50, 0.40/0.56, and 0.40/0.43, respectively. CONCLUSION: In recent-onset axSpA, SIJ erosions and erosion change were observed more frequently on MRI than radiography. The significance of interval improvement of MRI erosions warrants further research. [ClinicalTrials.gov: NCT01258738, NCT01648907].

Axial Spondyloarthritis Treatment Recommendations and Disease Activity Monitoring in Clinical Practice: Results of an Online Survey.

OBJECTIVE: Clinical practice guidelines are not always followed consistently. To better understand potential barriers to the implementation of treatment recommendations in axial spondyloarthritis and ankylosing spondylitis (axSpA/AS), an online survey was conducted. METHODS: Email invitations were sent to US rheumatology care providers in January 2023. The questionnaire included 20 questions, with an estimated completion time of 5-7 minutes. RESULTS: One hundred four of 441 (24%) invitees participated, including 80/104 (77%) board-certified rheumatologists and 20/104 (19%) fellows. Survey participants identified UpToDate (85%), treatment guidelines (74%), and colleagues (54%) as relevant sources of knowledge for managing axSpA/AS. Of the participants, 64% and 53% considered themselves to be at least moderately familiar with the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network (ACR/SAA/SPARTAN) and Assessment of Spondyloarthritis international Society/European Alliance of Associations for Rheumatology (ASAS/EULAR) treatment recommendations for axSpA/AS, respectively. Whereas 69% of participants agreed or strongly agreed that disease activity scores are useful for making treatment decisions in axSpA/AS, only 37% measure patient-reported outcomes (PROs) frequently (≥ 50% of clinic visits) while 82% do so for C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). PROs are typically recorded during clinic encounters (65%) and CRP/ESR are obtained after the visit (86%). Of the participants, 57% and 47% considered the Bath Ankylosing Spondylitis Disease Activity Index and Ankylosing Spondylitis Disease Activity Score to be at least moderately useful for measuring disease activity in axSpA/AS, respectively; 41% and 37% thought the same about the ASAS 20% improvement criteria and Clinical Disease Activity Index, respectively. CONCLUSION: Treatment guidelines are an important resource for rheumatologists who manage patients with axSpA/AS. Although there is general agreement that disease activity monitoring is important, the implementation of the respective recommendations is lacking. Reasons may include lack of familiarity and an underdeveloped infrastructure to efficiently collect PROs.

Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA. METHODS: We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool. RESULTS: Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo. CONCLUSION: Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.

Patient-tailored dose reduction of tumor necrosis factor inhibitors in axial spondyloarthritis.

Tumor necrosis factor inhibitors have been widely used in the field of axial spondyloarthritis, with current guidelines now recommending dose reduction instead of withdrawal of biologics. Systemic review and meta-analyses in literature have summarized present tapering strategies and principles in published heterogeneous studies. In this study, we reviewed and provided an update on present evidence based on prospective and retrospective studies from 2008 to 2022 by performing a literature review of related publications on remission or relapse from PubMed. We further stated the core issues concerning dose reduction, including the timing, optimization, intensity, maintenance, monitoring, factors associated with tapering and solutions to de-escalation failure. Remission/relapse should be the principal consideration in dose reduction implementation for individuals without comorbidities. As a treat-to-target scope of this multifaceted systemic disease, extra-articular manifestations such as uveitis, psoriasis, inflammatory bowel disease, cardiovascular complication, hip involvement and progressed structural damage influence patient-tailored dose reduction plans. Safety concerns and costs should be integrated into the decision-making schedule to optimize the individualized dose reduction paradigm.

Serum granulocyte-macrophage colony-stimulating factor (GM-CSF) is increased in patients with active radiographic axial spondyloarthritis and persists despite anti-TNF treatment.

BACKGROUND: Accumulating evidence supports the role of monocytes and neutrophils in radiographic axSpA (r-axSpA). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for both leukocyte lineages and a pro-inflammatory cytokine activating myeloid cells and promoting osteoclastogenesis. It acts through the JAK-STAT pathway. We measured serum GM-CSF and markers of bone metabolism in patients with r-axSpA before and after anti-TNF treatment. METHODS: Patients with active r-axSpA despite treatment with NSAIDs, all eligible for treatment with a biologic agent, were recruited. Healthy donors were sampled as controls. Serum was collected before (baseline) and after 4-6 months (follow-up) of anti-TNF treatment and the following molecules were measured with ELISA: GM-CSF, sclerostin (SOST), and dickkopf-1 (Dkk-1). RESULTS: Twelve r-axSpA patients (7 males, 5 females, median age 37 years) with a median disease duration of 1 year and 16 age- and sex-matched controls were included. At baseline, patients had mean BASDAI 6.3±2 and ASDAS 3.2±0.7, which decreased to 4.1±1.7 and 2.2±0.6 at follow-up, respectively. At baseline, r-axSpA patients had significantly higher mean serum levels of GM-CSF (150 vs 62pg/ml, p=0.049), significantly lower Dkk-1 (1228 vs 3052pg/ml, p=0.001), but similar levels of SOST (369 vs 544pg/ml, p=0.144) compared to controls. Anti-TNF treatment did not affect GM-CSF, Dkk-1, or SOST levels. Spearman correlation analysis showed that GM-CSF correlated positively with ASDAS at baseline (r=0.61, p=0.039), while no correlations were identified between bone markers (Dkk-1, SOST) on one hand and GM-CSF or disease activity indices on the other. CONCLUSIONS: GM-CSF is increased in patients with active AS and strongly correlates with disease activity. TNF inhibition does not affect GM-SCF levels, despite improving disease activity. GM-CSF may represent an important pathway responsible for residual inflammation during TNF blockade, but also a potential target of JAK inhibitors, explaining their efficacy in r-axSpA.

A Real-World Study on the Effect of Imrecoxib for Patients with Axial Spondyloarthritis.

Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) have generally been viewed as first-line therapy for axial spondyloarthritis (axSpA). Imrecoxib is a selective COX-2 inhibitor developed independently in China. At present, only one single-center RCT trial has shown that imrecoxib is equally effective as celecoxib in treating axSpA. Based on real-world data, our study aims to explore the efficiency of imrecoxib and TNF inhibitor (TNFi) combined with imrecoxib in treating axSpA. Patients and Methods: A total of 163 patients with axSpA who had more than two follow-up records in 6 months and treated with imrecoxib/celecoxib/TNFi combined with imrecoxib/TNFi combined with celecoxib from the First Affiliated Hospital of Anhui Medical University SpA Real World Database (AHSpA) were selected for analysis of our study. The linear mixed model was used to compare efficacy indexes before and after treatment and between different groups, adjust baseline measurement value and follow-up time. The Kaplan-Meier survival analysis was used to identify the differences in cumulative clinical remission rates between groups with different treatment at the follow-up period. Results: Results showed that after treatment ASDAScrp was slightly improved in imrecoxib group and celecoxib group within 6 months (p < 0.05). CRP, ESR, BASDAI, ASDAScrp, BASFI, occiput to wall distance and finger floor distance all significantly improved in TNFi combined with imrecoxib group and TNFi combined with celecoxib group within 6 months (all p < 0.05). According to the Kaplan-Meier survival curve and Log rank test analysis, the clinical remission rate was not significantly different between different treatment during 24-month follow-up (all p > 0.05). Conclusion: ASDAScrp improved slightly within 6 months after treatment with imrecoxib, and TNFi combined with imrecoxib significantly improved multiple effect indexes in axSpA patients. The efficacy of imrecoxib and celecoxib in the treatment of axSpA is equivalent. Also, they have the same efficacy after being combined with TNFi.

Sarcoidosis-like reaction secondary to adalimumab treatment in a patient with axial spondyloarthritis.

Anti-TNF agents, namely adalimumab, are safe drugs that represent an important arsenal in the treatment of immune-mediated inflammatory diseases. "Paradoxical effects" have been described with their use. A sarcoidosis "like" reaction induced by these agents is rare and is characterized by a systemic granulomatous reaction indistinguishable from sarcoidosis. We present a 55-year-old male patient, with axial spondyloarthritis, treated with with adalimumab. About 17 months under this therapy, he complained of dry cough and wheezing. Chest CT showed a peri-lymphatic and pericisural micronodular pattern and hilo-mediastinal lymph nodes, suggestive of sarcoidosis. Angiotensin converting enzyme was increased. Assuming the hypothesis of a sarcoidosis-like reaction secondary to adalimumab this therapy was discontinued with progressive improvement in the patient's complaints and in the radiological changes.

Measurement of pre-treatment inflammatory cytokine levels is valuable for prediction of treatment efficacy to tumor necrosis factor inhibitor in axial spondyloarthritis patients.

AIM: To evaluate the correlation of inflammatory cytokines with the treatment response to tumor necrosis factor inhibitor (TNFi) in axial spondyloarthritis (axSpA) patients. METHODS: This study enrolled 86 axSpA patients and 20 healthy controls (HCs). Inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-12, IL-17A, IL-21, IL-23, and IL-32 were determined in serum samples of axSpA patients before treatment and in HCs after enrollment. All patients received 40 mg adalimumab every 2 weeks for 12 weeks; meanwhile, ASAS40 (40 criteria of the Assessment by the SpondyloArthritis International Society) response rates were evaluated at weeks 2, 4, 8, and 12. RESULTS: Most inflammatory cytokines were elevated in axSpA patients compared with HCs (all P < 0.05) except for IL-32 (P = 0.101). In axSpA patients, ASAS40 response rates were 0%, 19.5%, 34.5%, 47.1%, and 56.3% at weeks 0, 2, 4, 8, and 12, respectively. Baseline [interquartile range] IL-6 (47.3 [32.5-53.4] pg/mL vs 31.7 [23.0-50.9] pg/mL, P = 0.005) and IL-17A (127.9 [90.7-149.5] pg/mL vs 96.6 [56.1-112.6] pg/mL, P < 0.001) were higher in axSpA patients with ASAS40 response compared with those without ASAS40 response, while baseline TNF-α, IL-1ß, IL-12, IL-21, IL-23, and IL-32 were not different between them (all P > 0.050). Multivariate logistic regression analysis disclosed that baseline IL-17A (P = 0.037), C-reactive protein (P = 0.012), and history of TNF inhibitor (P = 0.029) were independently associated with ASAS40 response. Furthermore, baseline IL-17A, C-reactive protein, history of TNFi, and their combination had an acceptable to good ability for predicting ASAS40 response. CONCLUSION: Measurement of pre-treatment inflammatory cytokine levels is valuable for predicting treatment efficacy of TNFi in axSpA patients.

Nonsteroidal anti-inflammatory drug-sparing effect of secukinumab in patients with radiographic axial spondyloarthritis: 4-year results from the MEASURE 2, 3 and 4 phase III trials.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain and inflammation, and are considered the cornerstone of pharmacological intervention in patients with radiographic axial spondyloarthritis (r-axSpA); however, the long-term use of NSAIDs is debatable due to their restricted therapeutic potential and the risk of side effects and complications. Therefore, reduction in NSAID intake is desirable in r-axSpA patients. Here, we report the long-term NSAID-sparing effect of secukinumab over 4 years in patients with r-axSpA. This post hoc analysis pooled data from 3 secukinumab trials (MEASURE 2-4) for each secukinumab maintenance dose of 150 and 300 mg, regardless of the loading dose regimen being i.v. or s.c. NSAID intake was evaluated prospectively using the Assessment of SpondyloArthritis International Society (ASAS)-NSAID score. Patients with an ASAS-NSAID score > 0 at baseline were analysed. NSAID-sparing endpoints included the mean change in the ASAS-NSAID score, the proportion of patients achieving 50% reduction, and the proportion of patients with an ASAS-NSAID score < 10. Percentages of patients who achieved BASDAI ≤ 2 were also assessed. Overall, 562 patients were included in this pooled analysis (secukinumab: 150 mg, N = 467; 300 mg, N = 95). The mean ASAS-NSAID score decreased with time in both the secukinumab 150 mg and 300 mg dose groups. The proportion of patients who achieved 50% reduction in the ASAS-NSAID score and clinically meaningful reduction of ASAS-NSAID score < 10 increased with time in both dose groups and in both low and high NSAID intake patients. The percentage of patients with a clinically relevant improvement (BASDAI ≤ 2) was consistently higher in patients with an ASAS-NSAID score < 10 than in patients with an ASAS-NSAID score ≥ 10. Secukinumab provided sustained, long-term NSAID-sparing effects in patients with r-axSpA for up to 4 years of treatment, as measured using the ASAS-NSAID score. Trial registered at clinicaltrials.gov: NCT01649375 ( https://clinicaltrials.gov/ct2/show/NCT01649375 ); NCT02008916 ( https://clinicaltrials.gov/ct2/show/NCT02008916 ); NCT02159053 ( https://clinicaltrials.gov/ct2/show/NCT02159053 ).

Significance of structural changes in the sacroiliac joints of patients with axial spondyloarthritis detected by MRI related to patients symptoms and functioning.

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that manifests primarily in the axial skeleton, initially mostly in the sacroiliac joints (SIJ), usually later spreading to the spine. The disease is characterised by inflammation and new bone formation which are mainly assessed by conventional radiography (CR) and magnetic resonance imaging (MRI). Tumour necrosis factor inhibitors (TNFi) and interleukin-17 antagonists have been shown to be efficacious and efficient in patients with axSpA. This treatment seems to also inhibit structural damage, for example, retard radiographic progression. Indeed, a reduction of new bone formation in the spine, as assessed by CR, has been reported to occur after at least 2 years of therapy with TNFi. Recently, a reduction of erosions and ankylosis in the SIJ has also been observed in axSpA patients treated with etanercept and filgotinib. In this narrative review, we discuss the limited significance of such findings.

No efficacy of anti-IL-23 therapy for axial spondyloarthritis in randomised controlled trials but in post-hoc analyses of psoriatic arthritis-related 'physician-reported spondylitis'?

The three monoclonal antibodies ustekinumab, guselkumab and risankizumab targeting the p 40 or the 19 subunit of interleukin -23 have now been approved for the indication psoriasis and the former two also for psoriatic arthritis (PsA). Ustekinumab and risankizumab have appeared ineffective in randomised controlled trials with patients with axial spondyloarthritis (axSpA), but post-hoc analyses of PsA trials have now suggested that they may improve back pain symptoms potentially induced by axial inflammation based on PsA. Here we argue that, based on the absence of efficacy in axSpA, this is unlikely and more probably due to generic, non-specific effects, which are not adequately covered by the tools developed for the assessment of inflammation in axSpA.

Long-term tolerability and efficacy of golimumab in active non-radiographic axial spondyloarthritis: results from open-label extension.

OBJECTIVES: We report the open-label extension (OLE) of the GO-AHEAD study evaluating the long-term efficacy and safety of golimumab (GLM) in patients with non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: Patients [both GLM- and placebo (PBO)-treated in the double-blind phase] received GLM 50 mg every 4 weeks during the OLE (36-week treatment; additional 8-week safety follow-up; GLM/GLM and PBO/GLM groups). All patients who entered and received ≥1 dose of study treatment in the OLE were included in the efficacy and safety analyses. The primary efficacy evaluations were the proportions of patients achieving 20% and 40% improvement in the ASAS criteria (ASAS20 and ASAS40, respectively). Responders' analyses were calculated using a non-responder imputation approach. RESULTS: Of 198 patients randomised, 189/198 (95.5%) entered the OLE; 174/198 patients (87.9%) completed all visits. Although the proportion of responders increased from week 16 to week 52 in the OLE in both GLM/GLM and PBO/GLM groups, the GLM/GLM group had a higher proportion of responders than the PBO/GLM group throughout the OLE from week 16 to week 52 (ASAS20: 71.1% to 83.9% vs 40.0% to 75.0%, respectively; ASAS40: 56.7% to 76.3% vs 23.0% to 59.4%, respectively; ASAS partial remission: 33.0% to 53.8% and 18.0% to 45.8%). In the OLE, the overall incidence of AEs was lower in the GLM/GLM vs PBO/GLM groups (41.9% and 54.2%). CONCLUSIONS: Sustained improvement in clinical efficacy was observed at 52 weeks in patients with nr-axSpA following GLM treatment. GLM was well tolerated and provided substantial long-term benefits to patients with nr-axSpA. TRIAL REGISTRATION: NCT01453725; United States National Library of Medicine clinical trials database; www.clinicaltrials.gov.