Active Axial Spondyloarthritis Research Articles

Rapid and Sustained Effect of Ixekizumab on Patient Global, Spinal Pain, Stiffness, and Fatigue in Chinese Patients with Radiographic Axial Spondyloarthritis.

Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase3 study in China. In this Chinese phase3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80mg every 4weeks (IXEQ4W; starting dose 160mg) or placebo for 16weeks. At week16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week16. Improvements were maintained through week52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. ClinicalTrials.gov identifier NCT04285229.

Granulocyte-macrophage colony-stimulating factor neutralisation in patients with axial spondyloarthritis in the UK (NAMASTE): a randomised, double-blind, placebo-controlled, phase 2 trial

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial spondyloarthritis. Namilumab is a human IgG1 monoclonal anti-GM-CSF antibody that potently neutralises human GM-CSF. We aimed to assess the efficacy of namilumab in participants with moderate-to-severe active axial spondyloarthritis. This proof-of-concept, randomised, double-blind, placebo-controlled, phase 2, Bayesian (NAMASTE) trial was done at nine hospitals in the UK. Participants aged 18-75 years with axial spondyloarthritis, meeting the Assessment in SpondyloArthritis international Society (ASAS) criteria and the ASAS-defined MRI criteria, with active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), were eligible. Those who had inadequately responded or had intolerance to previous treatment with an anti-TNF agent were included. Participants were randomly assigned (6:1) to receive subcutaneous namilumab 150 mg or placebo at weeks 0, 2, 6, and 10. Participants, site staff (except pharmacy staff), and central study staff were masked to treatment assignment. The primary endpoint was the proportion of participants who had an ASAS ≥20% improvement (ASAS20) clinical response at week 12 in the full analysis set (all randomly assigned participants). This trial is registered with ClinicalTrials.gov (NCT03622658). From Sept 6, 2018, to July 25, 2019, 60 patients with moderate-to-severe active axial spondyloarthritis were assessed for eligibility and 42 were randomly assigned to receive namilumab (n=36) or placebo (n=six). The mean age of participants was 39·5 years (SD 13·3), 17 were women, 25 were men, 39 were White, and seven had previously received anti-TNF therapy. The primary endpoint was not met. At week 12, the proportion of patients who had an ASAS20 clinical response was lower in the namilumab group (14 of 36) than in the placebo group (three of six; estimated between-group difference 6·8%). The Bayesian posterior probability η was 0·72 (>0·927 suggests high clinical significance). The rates of any treatment-emergent adverse events in the namilumab group were similar to those in the placebo group (31 vs five). Namilumab did not show efficacy compared with placebo in patients with active axial spondyloarthritis, but the treatment was generally well tolerated. Izana Bioscience, NIHR Oxford Biomedical Research Centre (BRC), NIHR Birmingham BRC, and Clinical Research Facility.

Efficacy and safety of iguratimod combined with celecoxib in active axial spondyloarthritis: a randomized, double-blind, placebo-controlled study

Objective To assess the efficacy and safety of iguratimod in adult patients with active axial spondyloarthritis (axSpA). Method This randomized, double-blind, placebo-controlled clinical trial lasted for 28 weeks. Patients with axSpA were randomized 1:1 to receive iguratimod 25 mg twice daily or a placebo. All patients also took celecoxib 200 mg twice daily for the first 4 weeks and on demand from 4 to 28 weeks. The primary endpoints were ASAS20 at 4 weeks and the non-steroidal anti-inflammatory drug (NSAID) index at 28 weeks. Other assessment variables included ASAS40, ASAS5/6 response rates, Spondyloarthritis Research Consortium of Canada (SPARCC) scores, and adverse events. Results In total, 35 patients completed the study and were included for analyses. The median (interquartile range) NSAID index was 43.8 (34.9–51.8) in the iguratimod group, which is significantly lower than 68.9 (42.5–86.4) in the placebo group (p = 0.025). ASAS response rates and changes in disease activity scores were similar between the iguratimod and placebo groups. Patients in the iguratimod group had more improvement in median (interquartile range) SPARCC scores for sacroiliac joints than did those in the placebo group [71% (54–100%) vs 40% (0–52%), p = 0.006]. Iguratimod combined with celecoxib was not associated with a greater risk of adverse effects than was monotherapy with celecoxib. No severe adverse events occurred. Conclusions In the treatment of active axSpA, iguratimod has a potential NSAID-sparing effect, and may also reduce magnetic resonance imaging-assessed bone marrow oedema in sacroiliac joints. Iguratimod provides an additional treatment option for patients with active axSpA.Clinical trial registration numberChiCTR2000029112, Chinese Clinical Trial Registry (http://www.chictr.org.cn)

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.

Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was tocompare 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). 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. 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. 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.

E068 Achievement of low disease activity over 52 weeks in patients with active axial spondyloarthritis on bimekizumab treatment: results from the phase 3 studies BE MOBILE 1 and BE MOBILE 2

Abstract Background/Aims The recommended treatment target for axial spondyloarthritis (axSpA) is remission/low disease activity (LDA) according to Ankylosing Spondylitis Disease Activity Score (ASDAS) levels (ASDAS<2.1); however, remission is difficult to achieve for many patients. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) remains commonly used in clinical practice to assess disease activity, although limited data exist to validate cut-offs. Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. BKZ has demonstrated consistent and sustained efficacy up to Week (Wk)52 in the BE MOBILE 1 and 2 phase 3 studies, including achievement of LDA according to ASDAS by > 50% of patients with non-radiographic (nr-)axSpA and radiographic (r-)axSpA. Here, we report achievement of LDA, as assessed by either ASDAS<2.1, BASDAI<4, or both, to Wk52 with BKZ across the spectrum of axSpA in two phase 3 studies. Methods BE MOBILE 1 (NCT03928704) and BE MOBILE 2 (NCT03928743) comprised a 16-wk placebo (PBO)-controlled and 36-wk maintenance period. BE MOBILE 1 (nr-axSpA) patients met Assessment of SpondyloArthritis international Society (ASAS) classification criteria and had objective inflammation (MRI and/or elevated C-reactive protein). BE MOBILE 2 (r-axSpA) patients met modified New York and ASAS classification criteria. All patients had active disease (BASDAI≥4 and spinal pain≥4 [BASDAI item 2]) at baseline. Patients were randomised to subcutaneous BKZ 160 mg every 4 weeks (Q4W) or PBO. Patients randomised to PBO switched to BKZ from Wk16 (‘PBO/BKZ-switchers’). The proportion of patients that achieved LDA to Wk52, as defined by either ASDAS<2.1, BASDAI<4, or both, are presented (non-responder imputation). Results Overall, 254 patients with nr-axSpA (BKZ: 128/PBO: 126) and 332 with r-axSpA (BKZ: 221/PBO: 111) were randomised. Most had high (ASDAS≥2.1-≤3.5) or very high (ASDAS>3.5) disease activity at baseline (nr-axSpA: BKZ: 99.2%/PBO: 97.6%; r-axSpA: BKZ: 98.6%/PBO: 100%). At Wk16, a greater proportion of BKZ vs PBO-treated patients achieved ASDAS<2.1 (nr-axSpA: BKZ: 46.1%/PBO: 19.8%; r-axSpA: BKZ: 42.1%/PBO: 17.1%), BASDAI<4 (nr-axSpA: BKZ: 52.3%/PBO: 31.7%; r-axSpA: BKZ: 55.7%/PBO: 41.4%) and both (nr-axSpA: BKZ: 43.8%/PBO: 19.0%; r-axSpA: BKZ: 41.6%/PBO: 17.1%). Results were sustained/improved across continuous BKZ-treated patients and PBO/BKZ-switchers to Wk52, with achievement of ASDAS<2.1 (nr-axSpA: BKZ: 53.9%/switchers: 47.6%; r-axSpA: BKZ: 50.2%/switchers: 61.3%), BASDAI<4 (nr-axSpA: BKZ: 60.2%/switchers: 54.0%; r-axSpA: BKZ: 65.6%/switchers: 68.5%) and both (nr-axSpA: BKZ: 49.2%/switchers: 45.2%; r-axSpA: BKZ: 49.8%/switchers: 58.6%). Achievement of BASDAI<4 was consistently higher than ASDAS<2.1, regardless of treatment arm. Conclusion Across the full axSpA disease spectrum, BKZ resulted in rapid achievement of LDA vs PBO to Wk16, as assessed by ASDAS<2.1, BASDAI<4, or both; improvements continued to Wk52. Most patients achieving ASDAS<2.1 also achieved BASDAI<4. These data suggest ASDAS<2.1 is a more stringent criterion for LDA, relevant for consideration of BKZ in the context of a potential treat-to-target approach for axSpA in daily practice. Disclosure X. Baraliakos: Consultancies; AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer and UCB Pharma ; grant/research support from: Novartis and UCB Pharma. Member of speakers’ bureau; AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma. Other; Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma. S. Ramiro: Grants/research support; AbbVie, Galapagos, MSD, Novartis, Pfizer and UCB Pharma; Consultant for AbbVie, Eli Lilly, Novartis, Pfizer, Sanofi and UCB Pharma. M. Magrey: Consultancies; AbbVie, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, BMS and UCB Pharma. M. Rudwaleit: Consultancies; AbbVie, Eli Lilly, Novartis and UCB Pharma. Member of speakers’ bureau; AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. N. Haroon: Consultancies; AbbVie, Eli Lilly, Janssen, Novartis and UCB Pharma. C. Fleurinck: Other; Employees of UCB Pharma. U. Massow: Other; Employees of UCB Pharma. N. de Peyrecave: Other; Employees of UCB Pharma. T. Vaux: Other; Employees of UCB Pharma. H. Marzo-Ortega: Consultancies; AbbVie, Biogen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB Pharma. Honoraria; AbbVie, Biogen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB Pharma. Grants/research support; Janssen, Novartis and UCB Pharma. V. Navarro-Compán: Consultancies; AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie and Novartis.

Comparative analysis of the efficacy of seniprutug (BCD-180) and adalimumab in the treatment of active radiographic axial spondyloarthritis: results of a systematic review and matching-adjusted indirect comparison

Objective: to compare the clinical efficacy of seniprutug (BCD-180) and adalimumab (ADA) in the treatment of adults with active radiographic axial spondyloarthritis (r-axSpA).Materials and methods. Based on the results of a previously conducted systematic review, an unanchored matching-adjusted indirect comparison (MAIC) was performed, adjusting for confounding factors. The analysis was based on the results of randomized placebo-controlled clinical trials of seniprutug (BCD-180-2/ELEFTA, NCT05445076) and ADA (ATLAS, NCT00085644) that met the selection criteria. We chose ASAS40 and ASAS20 measurements at week 24 as efficacy outcomes. Initial BASDAI and BASFI indices, proportion of women in the study population, time from disease onset, and baseline C-reactive protein (CRP) levels were considered as confounders.Results and discussion. The MAIC showed a statistically significant advantage in the clinical efficacy of seniprutug (BCD-180) over ADA. When adjusted, the odds ratios (OR) with 95% confidence intervals (CI) for seniprutug (BCD-180)/ADA were 1.86 (1.15; 3.02) and 2.21 (1.34; 3.72) for ASAS40 and ASAS20, respectively, at week 24.Conclusion. The MAIC demonstrated statistically significant superiority of seniprutug (BCD-180) over ADA on the key efficacy endpoints ASAS40 and ASAS20 at week 24 in adults with active r-axSpA. The inclusion of the innovative domestic drug seniprutug into treatment paradigm of active r-axSpA will potentially reduce the socio-economic burden of this disease by providing an affordable, effective and safe therapy while optimizing healthcare costs

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.

Certolizumab pegol in the treatment of axial spondyloarthritis.

Axial spondyloarthritis is a chronic, immune-mediated systemic inflammatory disease encompassing ankylosing spondylitis and nonradiographic axial spondyloarthritis. TNF inhibitors are the preferred second line therapy for patients with active axial spondyloarthritis. Certolizumab pegol is a TNFinhibitor approved for treatment of both. Three large phase III trials (RAPID-axSpA, C-axSpAndand C-OPTIMISE) and one large phase IV trial (CIMAX) establish its clinical efficacy in treatment of active disease and maintenance of remission for both diseases. Real world evidence demonstrates clinical efficacy and benefits including reduced bone loss, reduced risk of uveitis, safety in pregnancy and lactation and index drug survival of 10years. It is generally well tolerated, though can be associated with increased risk of serious infections.

Impact of body composition on clinical outcomes in patients with active radiographic axial spondyloarthritis under biological therapy.

To assess the association of body composition, evaluated by bioimpedance analysis (BIA), with disease activity, physical function, and mobility in patients with axSpA undergoing bDMARD treatment for one year. Patients with AS (radiographic axSpA) were enrolled in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to be candidates for bDMARD therapy at baseline presenting high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs. Outcomes (disease activity, function, and mobility) and body composition parameters were assessed at baseline and every 6 months thereafter. Body composition was assessed by BIA. The association between body composition parameters and outcomes over 1 year was analyzed using longitudinal generalized estimating equations. Seventy-four patients with radiographic axSpA were included in current analysis with a mean age of 36.5 years, disease duration of 6.2 years and ASDAS-CRP score of 3.4 at baseline. Fat mass value and fat mass index were positively associated with disease activity (ASDAS: ß = 0.01, 95% CI [-0.01, 0.03] and ß = 0.04, 95% CI [-0.01, 0.08], respectively) and functional disability (BASFI). Visceral adipose tissue (VAT) was associated with reduced spine mobility (BASMI: ß = 0.20, 95% CI [0.07, 0.33]). Additionally, increase in VAT and fat mass parameters was linked to worse disease activity and functional disability in women, while they were strongly associated with reduced spinal mobility in men. Higher levels of body fat and VAT were positively associated with increased disease activity, functional disability, and reduced spinal mobility in patients with radiographic axSpA treated with bDMARDs.

Comparative Effectiveness of Tofacitinib and Adalimumab in Axial Spondyloarthritis: A Real-World Clinical Context Multicenter Study.

Tofacitinib, an oral Janus kinase inhibitor, is a putative choice in the treatment of axial spondyloarthritis (AxSpA). The objective of this study was to compare the effectiveness and tolerability of tofacitinib with adalimumab, in AxSpA, in a real-world clinical setting. In this multicentric medical records review study, adult patients with active AxSpA treated with either tofacitinib 5 mg twice daily or adalimumab 40 mg subcutaneously fortnightly were recruited. Effectiveness was measured with Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Drug-cost analysis was calculated with Incremental Cost-Effectiveness Ratio (ICER drug ). Among the 266 patients, 135 were treated with tofacitinib and 131 with adalimumab (follow-up: 6.5 ± 1.6 months). Mean improvement of BASDAI (3.39 ± 0.09 vs. 3.14 ± 1.16, respectively) and that of ASDAS (1.78 ± 0.68 vs. 2.07 ± 2.08, respectively) were comparable between the adalimumab and tofacitinib groups. A higher proportion of patients achieved BASDAI50 response in the second (49.5% vs. 31.6%) and fourth month (83.9% vs. 62.8%) and ASDAS low disease activity in the fourth month (71.6% vs. 47.9%) in the adalimumab group. All disease activity measurements were similar by the sixth month in both groups. A higher proportion of patients in the tofacitinib group than in the adalimumab group required change in therapy (14.8% vs. 7.6%, respectively). ICER drug for adalimumab compared with tofacitinib was US $188.8 per patient in the adalimumab group for each person-month with BASDAI <4. Tofacitinib showed comparable effectiveness with adalimumab in patients with AxSpA at the sixth month, despite lesser response in the initial months, with favorable ICER drug .

Effectiveness and safety of BCD180, anti-TRBV9&lt;sup&gt;+&lt;/sup&gt; T-lymphocytes monoclonal antibody in patients with active radiographic axial spondyloarthritis: 36-week results of double-blind randomized placebo-controlled phase II clinical study ELEFTA

The aim – to evaluate the clinical effectiveness, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of seniprutug (BCD-180) in patients with radiographic active axial spondyloarthritis (r-axSpA, or ankylosing spondylitis).Subjects and methods. 260 patients with active r-axSpA and inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs) were randomized into three groups: seniprutug (BCD-180) at doses of 5 mg/kg or 7 mg/kg, or placebo. BCD-180 was administered on weeks 0–12–36. Patients in the placebo group were switched to BCD-180 at a dose of 5 mg/kg at week 24 and continued therapy at week 36. The primary endpoint was the proportion of patients achieving 40% improvement by Assessment in Spondyloarthritis International Society scale (ASAS40) at week 24. Secondary endpoints were proportion achieving ASAS20/40, improvement of 5 out of 6 criteria of ASAS (ASAS5/6), ASAS partial remission, clinically important improvement in ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein) (ASDAS-CII) and major improvement in ASDAS-CRP (ASDAS-MI). The dynamics of the disease activity status according to ASDAS-CRP, the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) indices, as well as the dynamics of laboratory markers (C-reactive protein anderythrocyte sedimentation rate (ESR)) were analyzed. Safety was assessed by the frequency and profile of adverse events (AEs) and adverse reactions (ARs).Results. The proportion of patients achieving ASAS40 at week 24 with seniprutug (BCD-180) at the dose of 7 mg/kg and 5 mg/kg was 51.4% and 40.8%, respectively, compared with 24% in the placebo group (p=0.0012 and p=0.0417, respectively). Analysis of secondary endpoints showed that in patients with r-axSpA, BCD-180 at both study doses was significantly superior to placebo at week 24 in the following measures: decrease in the proportion of subjects with very high disease activity (ASDAS-CRP&gt;3.5) achieving ASDAS-CII, ASAS20, ASAS5/6. A statistically significant decrease in the ASDAS-CRP, BASDAI, BASFI indices, as well as the concentration of CRP and ESR were demonstrated. Tolerability of seniprutug therapy was assessed as acceptable. Infusion reactions were the most common observed adverse events, the vast majority of which were mild to moderate in severity according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events) and developed predominantly during the first administration. The proportion of patients with binding antibodies was 5.1%. However, no neutralizing antibodies were detected.Conclusion. Seniprutug (BCD-180) demonstrated superiority over placebo in clinical efficacy with a favorable safety profile and low immunogenicity as a treatment of r-axSpA.

Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies

ObjectivesBimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial...

Efficacy of Tofacitinib in the Treatment of Axial Spondyloarthritis

Tofacitinib is a janus kinase enzyme inhibitor used in the treatment several inflammatory conditions. It orchestrates cytokine communication for numerous natural and adaptive immunological responses and underlie the intricate pathophysiology of AS, are directly bound by JAK inhibitors and their intracellular catalytic activity is controlled. For the medical care of older individuals with axial spondyloarthritis, tofacitinib, an oral JAK inhibitor, is being studied. Objective: To analyze the efficacy of tofacitinib in the treatment of axial spondylarthritis in adult patients. Methods: During the time frame of 1st November 2022 till 31st October 2023 at the department of rheumatology, Lady Reading Hospital, Peshawar, patients with active axial spondyloarthritis who fulfilled the modified New York criteria and who were refractory to NSAIDs were registered in this study. Patients were randomized to receive tofacitinib 5mg x BID for 12 weeks, or a placebo, in equal groups (A and B). The study's major end goal was the evaluation of Spondyloarthritis International Society responses evaluating a 20% improvement (ASAS20) at week 12. Results: 44 patients were enrolled (22 in each group). The mean age of tofacitinib arm was 41.19 ± 5.075 years versus 39.83 ± 4.989 years in placebo group. Tofacitinib was effective in 17 patients (77.3%) as compared to 07 patients (31.8%) in placebo group. Treatment response was significant higher (p = 0.002) with tofacitinib. Conclusions: Tofacitinib considerably out-performed a placebo when used to treat people with active axial spondyloarthritis.

EE192 The Cost-Effectiveness of a Bimekizumab Versus Secukinumab Treatment Pathway in Patients with Active Axial Spondyloarthritis in Scotland

EE192 The Cost-Effectiveness of a Bimekizumab Versus Secukinumab Treatment Pathway in Patients with Active Axial Spondyloarthritis in Scotland

Real-world effectiveness of golimumab in the treatment of patients with active rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who failed initial TNF-α inhibitor therapy: a pooled analysis of European prospective observational studie.

Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients often experience secondary non-response to a first-line tumour necrosis factor alpha inhibitor (TNFαi). This pooled analysis of six observational studies in Europe (GO-BEYOND program) provides an estimate of second-line golimumab (GLM) effectiveness for these rheumatic diseases. The GO-BEYOND studies included common disease-specific endpoints allowing for a pooled analysis. Patients had discontinued one prior TNFαi (due to loss of efficacy, tolerability, or inconvenience) and were followed for 12 months after GLM initiation. Primary endpoints included the proportion of patients achieving low disease activity (LDA, DAS28-CRP<3.2) in RA, minimal disease activity (MDA, fulfilment of 5 of 7 outcome measures) in PsA, or low disease activity (ASDAS<2.1) in axSpA at 6 months. Disease activity at 3 and 12 months and quality of life (QoL; EQ-5D-3L) were also assessed. Adverse events were monitored. Protocol-specified analyses were based on observed data. In 712 patients, (n=325, RA; 186, PsA; 201, axSpA), mean age was 54 years, 64% were female, and median disease duration was 5 years. Primary endpoints were achieved in 58.3% (RA), 45.5% (PsA), and 45.4% (axSpA) of patients; disease activity improvements were observed at 3 and 12 months and EQ-5D-3L results showed improved QoL over time. The treatment persistence rate at 12 months was 67.8% of patients. No new safety signals were observed. This pooled analysis of the GO-BEYOND studies showed that treatment with GLM was effective and represented a valid second-line option for RA, PsA, and axSpA patients.

Deciphering in vivo metabolic profile and pharmacological mechanisms of Jitongning Tablet for the treatment of Ankylosing spondylitis

Jitongning tablet (JTNT) is a Traditional Chinese Medicine (TCM) prescription used for the treatment of Ankylosing spondylitis (AS). Currently, it is in phase II clinical trial (NCT03932019) for patients with active axial Spondyloarthritis (axSpA), showing great promise for the treatment of AS. However, the potential material basis and the underlying mechanisms for JTNT to treat AS remain elusive. Here, we performed UPLC-Q-TOF-MS to determine the in vivo metabolic profile of JTNT in rats and conducted in vivo studies including acetic acid-induced writhing, hot plate models, and collagen-induced arthritis (CIA) in rats to evaluate and validate the analgesic and anti-inflammatory effects of JTNT, two main symptoms for AS. Additionally, network pharmacology combined with molecular docking was performed to investigate the potential underlying mechanisms. As a result, a total of 116 xenobiotics were identified from the plasma, urine, and brain tissues of rats after oral administration of JTN extracts. Pharmacological evaluation revealed that fractions JTN-3 and JTN-4 exerted significant analgesic activities by reducing the number of writhes in an acetic acid-induced writhing mice model. JTN extract also exerted excellent therapeutic effects in the CIA model by ameliorating paw edema and decreasing systemic manifestation of inflammation and the level of circulating immune complex (CIC) and interferon γ (IFN-γ). Fractions of JTN extract, especially JTN-2 and JTN-4, on the other hand, ameliorated the secondary lesions caused by chicken type II collagen (CII) to a certain extent. Further, network pharmacology combined with molecular docking suggested crucial roles of inflammation and immune-related genes such as MAPK1, MAPK14, NOS3, and RELA in the treatment of AS by JTNT. In conclusion, our studies suggest that the isoquinoline and diterpenoid alkaloids from Corydalis Rhizoma and Aconiti Radix Cocta, along with coumarins from Angelicae Pubescentis Radix, may be the main bioactive components, and the AS treatment mechanism may mainly involve immune regulation of JTNT. These results help clarify the potential material basis and underlying mechanisms of JTNT for the treatment of AS, facilitating the broad application of this TCM in clinical practice.

Achievement of higher thresholds of clinical responses and lower levels of disease activity is associated with improvements in workplace and household productivity in patients with axial spondyloarthritis.

Patients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve upon treatment. The objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA. RAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA. The impact of axSpA on workplace and household productivity was evaluated using the validated arthritis-specific Work Productivity Survey. Outcomes included the percentage of patients achieving Assessment of SpondyloArthritis International Society (ASAS) response and Ankylosing Spondylitis Disease Activity Score (ASDAS) thresholds. This post hoc study used a generalised estimating equations model to determine the association between the threshold of clinical response achieved and patient productivity. Of 218 CZP-randomised patients, 65.1% completed week 204. At baseline, 72.0% were employed outside the home. Of the patients who were unemployed, 42.6% were unable to work due to arthritis. Achievement of higher treatment response thresholds, such as clinical remission, was associated with fewer days affected by workplace absenteeism (ASAS-partial remission: 4.0 days, ASAS40: 8.6 days, ASAS20 but not reaching ASAS40 response: 29.4 days, ASAS20 non-response: 69.2 days; ASDAS-inactive disease: 5.0 days, ASDAS-low disease activity: 15.6 days, ASDAS-high disease activity: 32.7 days, ASDAS-very high disease activity: 93.4 days). Similar associations were found for workplace presenteeism, and household absenteeism and presenteeism. Over 4 years, achievement of higher clinical response thresholds and lower levels of disease activity was associated with fewer cumulative days affected by absenteeism or presenteeism, with clinical remission associated with the greatest improvements in productivity. This highlights the importance of targeting these thresholds to limit the burden of axSpA on society and on patients' daily lives.

The use of tenoxicam in active axial spondyloarthritis – focus on efficacy and safety

Purpose of the study – to study the efficacy and safety of tenoxicam (Texared®) in patients with active axial spondyloarthritis.Material and methods. The study included 35 patients with active axial spondyloarthritis with BASDAI≥4.0. Patients were given continuous oral tenoxicam (Texared®, Dr. Reddy’s Laboratories) at a dosage of 20 mg/day. Subsequently, 5 patients were excluded from the study due to discontinuation of the drug after 5–10 days of administration. 30 patients were included in the final analysis. Initially and after 30 days, to assess the severity of pain and stiffness, activity, patients filled out questionnaires in electronic form using Google forms, a general assessment of pain in the lower back and the intensity of night pain by the patient, subjective sleep characteristics were carried out. The doctor calculated the BASDAI, ASDAS-CRP, BASMI indices, and evaluated the activity according to the doctor’s opinion. The baseline blood pressure level was determined, and a patient diary was issued for ambulatory blood pressure measurement in the morning/evening for 30 days. After 30 days, the patient’s ambulatory blood pressure control was assessed. At baseline and after 30 days, biochemical blood parameters were studied, including a complete blood and urine test.Results and conclusion. In patients with axial spondyloarthritis with high and very high activity, a positive effect of tenoxicam (Texared®) therapy on disease activity was noted. The effect of Texared® develops with regular use already during the first 2 weeks, and after 4 weeks there is a clear decrease in the severity of pain in the lower back, a decrease in the duration of morning stiffness. The drug is well tolerated, has a favorable safety profile, no serious adverse events and few side effects that do not require discontinuation of therapy.

PCR196 Association of Clinical Response Criteria and Disease Activity Levels With Physical Function and HRQoL in Patients With Active Axial Spondyloarthritis: 16-Week Results From Two Phase 3 Randomised, Placebo-Controlled Studies

To examine the association of clinical response criteria and disease activity levels with changes in physical function and health-related quality of life (HRQoL) in patients with axial spondyloarthritis (axSpA).

Effects of ixekizumab treatment on structural changes in the sacroiliac joint: MRI assessments at 16 weeks in patients with non-radiographic axial spondyloarthritis.

There is limited understanding regarding the inhibition of structural damage in the sacroiliac joint of patients with non-radiographic axial spondyloarthritis. This study evaluated the effect of the interleukin-17A inhibitor ixekizumab versus placebo on structural lesions in the sacroiliac joints as assessed by MRI at week 16 in patients with non-radiographic axial spondyloarthritis from the COAST-X study. COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs. Patients were randomly allocated to placebo or double-blind ixekizumab 80 mg every 4 weeks (Q4W) or 2 weeks (Q2W), with an 80 mg or 160 mg starting dose. We report a post-hoc analysis of 266 patients with available MRI scans from baseline and week 16. MRI scans were scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint structural score (SSS) method independently by two masked readers. Treatment comparisons used analysis of covariance based on observed cases. Correlations were evaluated among changes in SPARCC SSS for erosion, fat lesions, and backfill, and between changes in SPARCC SSS and sacroiliac joint inflammation scores and clinical measures. COAST-X was registered with ClinicalTrials.gov, NCT02757352. Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled to the COAST-X study. 290 (96%) of 303 participants completed the week 16 visit (95 in the ixekizumab Q4W group, 98 in the ixekizumab Q2W group, and 97 in the placebo group), and MRI scans were available for 266 patients at baseline and week 16 (85 in the ixekizumab Q4W group, 91 in the ixekizumab Q2W group, and 90 in the placebo group). Changes from baseline to week 16 in mean SPARCC SSS for erosion were -0·39 for ixekizumab Q4W (p=0·003 vs placebo), -0·40 for ixekizumab Q2W (p=0·002), and 0·16 for placebo; for fat lesions: 0·16 for ixekizumab Q4W (p=0·013), 0·10 for ixekizumab Q2W (p=0·067), and -0·04 for placebo; and for backfill: 0·21 for ixekizumab Q4W (p=0·011), 0·22 for ixekizumab Q2W (p=0·006), and -0·10 for placebo. Ankylosis did not change. Effects of ixekizumab versus placebo on structural changes were most pronounced in patients with baseline inflammation in the sacroiliac joints. Changes from baseline at week 16 in erosion, fat lesions, and backfill were correlated. Although the clinical relevance is not yet clear, patients with non-radiographic axial spondyloarthritis receiving ixekizumab had significant reductions in erosions and increases in fat lesions and backfill in the sacroiliac joints versus placebo at week 16, suggesting an early repair process with ixekizumab treatment. Eli Lilly and Company.