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Objective: Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was to compare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin‐17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ‐ADL]; tumor necrosis factor inhibitor). Methods: Biologic‐naive patients with active radiographic axial SpA, at high risk of radiographic progression (high‐sensitivity C‐reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ‐ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ‐ADL at week 104 (primary endpoint), mean CFB‐mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. Results: Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ‐ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB‐mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ‐ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ‐ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. Conclusion: Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ‐ADL arms. The safety of both treatments was consistent with previous reports. [ABSTRACT FROM AUTHOR]

Objectives To compare the efficacy and safety of bimekizumab 160 mg every 4 weeks, a selective inhibitor of IL-17F and IL-17A, with those of biologic/targeted synthetic DMARDs (b/tsDMARDs) in non-radiographic axial SpA (nr-axSpA) and AS. Methods A systematic literature review identified randomized controlled trials until January 2023 for inclusion in Bayesian network meta-analyses (NMAs), including three b/tsDMARDs exposure networks: predominantly-naïve, naïve, and experienced. Outcomes were Assessment of SpondyloArthritis international Society (ASAS)20, ASAS40 and ASAS partial remission (PR) response rates at 12–16 weeks. A safety NMA investigated discontinuations due to any reason and serious adverse events at 12–16 weeks. Results The NMA included 36 trials. The predominantly-naïve network provided the most comprehensive results. In the predominantly-naïve nr-axSpA analysis, bimekizumab had significantly higher ASAS20 response rates vs secukinumab 150 mg [with loading dose (LD)/without LD], and comparable response rates vs other active comparators. In the predominantly-naïve AS analysis, bimekizumab had significantly higher ASAS40 response rates vs secukinumab 150 mg (without LD), significantly higher ASAS-PR response rates vs secukinumab 150 mg (with LD) and comparable response rates vs other active comparators. Bimekizumab demonstrated similar safety to that of other b/tsDMARDs. Conclusion Across ASAS outcomes, bimekizumab was comparable with most b/tsDMARDs, including ixekizumab, TNF inhibitors and upadacitinib, and achieved higher response rates vs secukinumab for some ASAS outcomes in predominantly b/tsDMARD-naïve nr-axSpA and AS patients at 12–16 weeks. In a pooled axSpA network, bimekizumab demonstrated comparable safety vs other b/tsDMARDs. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of tofacitinib in patients with ankylosing spondylitis (AS) by prior biologic disease‐modifying antirheumatic drug (bDMARD) use. Methods: Data from a placebo‐controlled, double‐blind study of patients with active AS were analyzed. Patients received tofacitinib 5 mg twice daily (BID) or placebo to week 16; all received open‐label tofacitinib 5 mg BID to week 48 and were stratified by prior treatment (bDMARD‐naive or tumor necrosis factor inhibitor [TNFi]–inadequate responder [IR], including bDMARD‐experienced [non‐IR]). Disease activity/safety were assessed throughout. Results: Of 269 patients, 207 (77%) were bDMARD‐naive; 62 (23%) were in the TNFi‐IR subgroup. TNFi‐IR patients had higher baseline BMI (28.0 vs. 26.1 kg/m2), longer symptom duration (14.4 vs. 13.2 years), and lower concomitant conventional synthetic DMARD use (14.5% vs. 30.9%) than bDMARD‐naive patients. At week 16, for most outcomes, tofacitinib efficacy exceeded placebo for both subgroups and was sustained to week 48. At week 16, tofacitinib versus placebo differences were similar between bDMARD‐naive and TNFi‐IR patients (Assessment in Spondyloarthritis international Society 40 treatment difference [95% confidence interval]: 30.8% [19.1%‐42.6%] vs. 19.4% [1.7%‐37.0%]). Adverse event (AE) proportions were similar between tofacitinib‐treated bDMARD‐naive/TNFi‐IR patients (77.5%/77.4%) at week 48 with no deaths. A numerically higher proportion of tofacitinib‐treated TNFi‐IR versus bDMARD‐naive patients discontinued study drug (12.9% vs. 3.9%) or dose reduced/temporarily discontinued due to AEs (19.4% vs. 11.8%). Conclusion: Tofacitinib efficacy exceeded placebo at week 16 for bDMARD‐naive/TNFi‐IR patients and was sustained to week 48. The absolute magnitude of responses was generally greater in bDMARD‐naive patients versus TNFi‐IR patients. More TNFi‐IR versus bDMARD‐naive patients discontinued or dose reduced/temporarily discontinued tofacitinib due to AEs. Small sample size and sample size differences between subgroups limited the interpretation. [ABSTRACT FROM AUTHOR]

Objective: To determine if the efficacy of biologics differ based on magnetic resonance imaging (MRI) and C‐reactive protein (CRP) findings. Methods: We compared four subgroups (MRI+/CRP+, MRI+/CRP−, MRI−/CRP+, MRI−/CRP−) from randomized controlled trials (RCTs). A comprehensive database search was performed to include axial spondylarthritis (axSpA; both radiographic axSpA [r‐axSpA] and nonradiographic axSpA [nr‐axSpA]) RCTs with treatment efficacy reported by different MRI and CRP subgroups. Study‐specific disease activity scores (at 12‐16 weeks) were pooled using a random‐effects model and compared between the four subgroups. Results: Five trials (all nr‐axSpA) were included: three with tumor necrosis factor inhibitors (TNFi, N = 729) and two with interleukin‐17 inhibitors (IL‐17i, N = 794). TNFi and IL‐17i showed efficacy based on the Assessment of Spondyloarthritis International Society 40 (ASAS40) and Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) in all MRI and CRP subgroups, except the CRP−/MRI− subgroup, which had a single study with only 39 patients. There was no statistically significant difference between the four subgroups in terms of patients achieving ASAS40 (P = 0.60, I2 = 0%) or BASDAI50 (P = 0.27, I2 = 23.9%). The number needed to treat was three for the CRP+/MRI+ and CRP+/MRI− subgroups and six for the CRP−/MRI+ and CRP−/MRI− subgroups. All trials had a low risk of bias. Between‐study heterogeneity was low to moderate. Sensitivity analyses comparing TNFi or IL‐17i versus placebo similarly showed no difference between subgroups in terms of ASAS40 (TNFi, P = 0.57; IL‐17i, P = 0.28) and BASDAI50 (TNFi, P = 0.37; IL‐17i, P = 0.18). Conclusion: In this systematic review, there was no statistically significant difference between the four subgroups in terms of efficacy based on ASAS40 or BASDAI50. [ABSTRACT FROM AUTHOR]

Background: 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. Objectives: 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. Design: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective: To assess the long‐term safety, tolerability, and efficacy of bimekizumab in patients with active ankylosing spondylitis (AS). Methods: Patients with active AS who completed the dose‐ranging, 48‐week BE AGILE randomized controlled trial were eligible to participate in an open‐label extension (OLE) study, in which patients received 160 mg of bimekizumab every 4 weeks. We present the safety and efficacy results through 156 weeks. Missing efficacy data were imputed using nonresponder imputation analysis for binary outcomes and multiple imputation for continuous outcomes. Results: From weeks 0–156, 280 of 303 patients (exposure‐adjusted incidence rate 141.0 per 100 patient‐years) experienced ≥1 treatment‐emergent adverse event; the most frequent adverse events were nasopharyngitis (8.1 per 100 patient‐years) and upper respiratory tract infection (5.0 per 100 patient‐years). Additionally, 67 of 303 patients (9.8 per 100 patient‐years) had mild to moderate localized fungal infections (28 of 303 patients had Candida infections [3.7 per 100 patient‐years] and 23 of 303 patients had oral candidiasis [3.0 per 100 patient‐years]), 10 patients had serious infections (1.3 per 100 patient‐years), and no cases of active tuberculosis were reported. Active inflammatory bowel disease (1.1 per 100 patient‐years), anterior uveitis (0.7 per 100 patient‐years), and adjudicated major adverse cardiovascular events (0.3 per 100 patient‐years) were infrequent. The efficacy of bimekizumab treatment demonstrated at week 48 was sustained in the OLE study. At week 156, nonresponder imputation analysis showed that 53.7% of patients (72.6% of observed cases) met the Assessment of SpondyloArthritis international Society criteria for 40% improvement and 28.0% of patients (37.9% of observed cases) achieved partial remission; Ankylosing Spondylitis Disease Activity Scores were reduced from baseline (mean ± SEM 3.9 ± 0.1) to week 48 (2.1 ± 0.1) and week 156 (1.9 ± 0.1) (multiple imputation). Patients showed sustained improvements in pain, fatigue, physical function, and health‐related quality of life. Conclusion: The safety profile of bimekizumab was found to be consistent with previously demonstrated findings, and no new safety signals were identified. The efficacy of bimekizumab in patients with AS was sustained through 3 years of treatment. Video Abstract [ABSTRACT FROM AUTHOR]

Objective To evaluate response rates at week 16 with ixekizumab in patients with radiographic axial SpA (r-axSpA) and elevated or normal/low baseline inflammation measured by serum CRP or spinal MRI using data from two randomized, double-blind, placebo (PBO)-controlled phase III trials. Methods Biologic-naïve (COAST-V) or TNF inhibitor-experienced (COAST-W) adults with active r-axSpA received 80 mg ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W) or PBO or active reference [40 mg adalimumab every 2 weeks (ADAQ2W) in COAST-V. At week 16, patients receiving ixekizumab continued as assigned and patients receiving PBO or ADA were rerandomized 1:1 to IXEQ2W or IXEQ4W through week 52. Assessment of SpondyloArthritis international Society 40% (ASAS40) response rates were examined by baseline CRP (≤5 or >5 mg/l) and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine inflammation score (<2 or ≥2). Results In the COAST-V/W integrated dataset (N  = 567), significantly more patients treated with ixekizumab achieved ASAS40 response at week 16 by CRP ≤5 mg/l (27% IXEQ4W, P  < 0.05; 35% IXEQ2W, P  < 0.01 vs 12% PBO), CRP >5 mg/l (39% IXEQ4W, P  < 0.001; 43% IXEQ2W, P  < 0.001 vs 17% PBO), SPARCC MRI spine score <2 (40% IXEQ4W P  < 0.01, 52% IXEQ2W P  < 0.001 vs 16% PBO), and SPARCC MRI spine score ≥2 (44% IXEQ4W P  < 0.001, 47% IXEQ2W P  < 0.001 vs 19% PBO). ASAS40 response was observed with CRP ≤5 mg/l and SPARCC MRI spine score <2 with IXEQ4W (29%) and was significant with IXEQ2W (48%; P  < 0.05) vs PBO (13%). Conclusion Ixekizumab demonstrated efficacy in the treatment of AS/r-axSpA in patients with and without elevated CRP or evidence of spinal inflammation on MRI. Trial registration ClinicalTrials.gov (https://clinicaltrials.gov): NCT02696785, NCT02696798 [ABSTRACT FROM AUTHOR]

Objective: The impact of the COVID‐19 pandemic on patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS), has been variable. Here, we assess disease activity and health‐related quality of life (HRQoL) through the pandemic in patients with AS. Methods: In the open‐label extension (OLE) of the phase 2b BE AGILE study, patients with AS received 160 mg of subcutaneous bimekizumab every 4 weeks. We assessed Ankylosing Spondylitis Disease Activity Score with C‐reactive protein (ASDAS‐CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Quality of Life (ASQoL) scores in the OLE immediately before and during the COVID‐19 pandemic (September 2019 to April 2021). Results: A total of 232 patients remained in the BE AGILE OLE and were included in this post hoc study at the start of the analysis period (September 1, 2019); 12 patients had a COVID‐19 treatment‐emergent adverse event, and no cases resulted in death. The number of missed bimekizumab doses due to COVID‐19 (11 doses) was minimal, and missed assessments remained low (≤5%) compared with the prepandemic period. Mean ASDAS‐CRP (1.8), BASDAI (2.4), and ASQoL scores (2.8) in the OLE were low at pre‐pandemic baseline and remained stable at 1.7 to 1.8, 2.2 to 2.4, and 2.0 to 2.8, respectively, across successive 3‐month periods immediately before and during the pandemic. ASDAS‐CRP, BASDAI, and ASQoL stability was consistent across major study countries. Conclusion: Disease activity and HRQoL remained stable during the COVID‐19 pandemic in patients with AS receiving bimekizumab in the BE AGILE OLE, with no indication of negative effects on these outcomes. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]