Safety Profile of Upadacitinib up to 5 Years in Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis: An Integrated Analysis of Clinical Trials.

INTRODUCTION: This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA]). METHODS: Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15 mg once daily and adalimumab 40 mg biweekly), AS (pooled upadacitinib 15 mg), nr-axSpA (upadacitinib 15 mg), and pooled axSpA (pooled upadacitinib 15 mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY). RESULTS: A total of 1789 patients (PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received ≥ 1 dose of upadacitinib 15 mg for 3689 PY of exposure or adalimumab (n = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases. CONCLUSION: Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified. TRIAL REGISTRATION: SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.

Psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis are a group of diseases that cause pain and inflammation of the joints and/or spine. Safety data were combined from five studies: two in psoriatic arthritis, two in ankylosing spondylitis, and one in non-radiographic axial spondyloarthritis. Patients were treated with upadacitinib or adalimumab for up to 5 years. Adalimumab was only used for patients participating in one of the two psoriatic arthritis studies. Side effects from treatment were more common in patients with psoriatic arthritis than those with ankylosing spondylitis and non-radiographic axial spondyloarthritis; more patients with psoriatic arthritis had side effects with upadacitinib than adalimumab. A similar number of patients across treatment groups and diseases had side effects that made them stop treatment. The number of cancer cases (except cancer of the upper layer of the skin), cardiovascular issues, and blood clots were similar between the upadacitinib and adalimumab groups in psoriatic arthritis and across diseases. Serious infections, painful rashes that cause blisters (herpes zoster, also commonly referred to as shingles), low levels of white blood cells, and cancer of the upper layer of the skin were more common with upadacitinib than adalimumab in patients with psoriatic arthritis; overall, these events occurred more often with upadacitinib in patients with psoriatic arthritis than with ankylosing spondylitis and non-radiographic axial spondyloarthritis. Our results showed that the safety of upadacitinib was generally similar across diseases, and patients could tolerate it well for up to 5 years. No new safety risks were found with upadacitinib treatment.

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.

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.

Multimorbidity phenotypes in ankylosing spondylitis and their association with disease activity and functional impairment: Data from the prospective study of outcomes in ankylosing spondylitis cohort.

OBJECTIVES: To examine the association of multimorbidity phenotypes at baseline with disease activity and functional status over time in ankylosing spondylitis (AS). METHODS: Patient-reported AS morbidities (comorbidities, N = 28 and extra-musculoskeletal manifestations, EMMs, N = 3) within 3 years of enrollment with a prevalence ≥1 %, were included from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort. We defined multimorbidity as ≥2 morbidities (MM2+) and substantial multimorbidity as ≥5 morbidities (MM5+). Multimorbidity clusters or phenotypes were identified using K-median clustering. Disease activity (ASDAS-CRP) and functional status (BASFI) measures were collected every 6 months. Generalized estimating equation method was used to examine the associations of multimorbidity counts and multimorbidity clusters with measures of disease activity and functional status over time. RESULTS: Among 1,270 AS patients (9,885 visits) with a median follow-up of 2.9 years (IQ range: 1.0-6.8 years), the prevalence of MM2+ and MM5+ was 49 % and 9 % respectively. We identified five multimorbidity clusters: depression (n = 321, 25 %), hypertension (n = 284, 22 %), uveitis (n = 274, 22 %), no morbidities (n = 238, 19 %), and miscellaneous (n = 153, 12 %). Patients in the depression cluster were more likely to be female and had significantly more morbidities and worse disease activity and functional status compared to those with no morbidities. CONCLUSION: Approximately 49 % of AS patients in the PSOAS cohort had multimorbidity and five distinct multimorbidity phenotypes were identified. In addition to the number of morbidities, the type of morbidity appears to be important to longitudinal outcomes in AS. The depression cluster was associated with worse disease activity and function.

Goodbye to the term 'ankylosing spondylitis', hello 'axial spondyloarthritis': time to embrace the ASAS-defined nomenclature.

Ankylosing spondylitis (AS) is the historic term used for decades for the HLA-B27-associated inflammatory disease affecting mainly the sacroiliac joints (SIJ) and spine. Classification criteria for AS have radiographic sacroiliitis as a dominant characteristic. However, with the availability of MRI of SIJ, it could be demonstrated that the disease starts long before definite SIJ changes become visible on radiographs. The Assessment of SpondyloArthritis international Society, representing a worldwide group of experts reached consensus on changes in the nomenclature pertaining to axial spondyloarthritis (axSpA), such as the terminology of diagnosis and of assessment of disease activity tools. These are important changes in the field, as experts in axSpA are now in agreement that the term axSpA is the overall term for the disease. A further differentiation, of which radiographic versus non-radiographic is only one aspect, may be relevant for research purposes. Another important decision was that the terms AS and radiographic axSpA (r-axSpA) can be used interchangeably, but that the preferred term is r-axSpA. Based on the decision that axSpA is the correct terminology, a proposal was made to officially change the meaning of the ASDAS acronym to 'Axial Spondyloarthritis Disease Activity Score'. In addition, for simplification it was proposed that the term ASDAS (instead of ASDAS-CRP) should be preferred and applied to the ASDAS calculated with C reactive protein (CRP). It is hoped that these changes will be used consequently for education, in textbooks, manuscripts and presentations.

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.

OBJECTIVES: Bimekizumab (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 spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52. METHODS: BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks. RESULTS: Improvements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%). CONCLUSIONS: At Week 52, dual inhibition of IL-17A and IL-17F with BKZ resulted in sustained efficacy across the axSpA spectrum; the safety profile was consistent with the known safety of BKZ. TRIAL REGISTRATION NUMBER: NCT03928704; NCT03928743.

Comparative efficacy and safety of bimekizumab in axial spondyloarthritis: a systematic literature review and network meta-analysis.

OBJECTIVES: To compare the efficacy and safety of bimekizumab 160 mg every 4 weeks, a selective inhibitor of interleukin­17F and 17A, with biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS). METHODS: A systematic literature review identified randomised 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 other b/tsDMARDs. CONCLUSION: Across ASAS outcomes, bimekizumab was comparable to 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.

Tofacitinib Efficacy and Safety in Patients With Ankylosing Spondylitis by Prior Biologic Disease-Modifying Antirheumatic Drug Use: A Post Hoc Analysis.

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.

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.

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.

Effect of Biologics in Subgroups of Axial Spondyloarthritis Based on Magnetic Resonance Imaging and C-Reactive Protein: A Systematic Review and Meta-Analysis.

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.

Two-year imaging outcomes from a phase 3 randomized trial of secukinumab in patients with non-radiographic axial spondyloarthritis.

BACKGROUND: Radiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are reported here. METHODS: In the PREVENT study, adult patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for nr-axSpA with elevated CRP and/or MRI inflammation received secukinumab 150 mg or placebo. All patients received open-label secukinumab from week 52 onward. Sacroiliac (SI) joint and spinal radiographs were scored using the modified New York (mNY) grading (total sacroiliitis score; range, 0-8) and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; range, 0-72), respectively. SI joint bone marrow edema (BME) was assessed using the Berlin Active Inflammatory Lesions Scoring (0-24) and spinal MRI using the Berlin modification of the AS spine MRI (ASspiMRI) scoring (0-69). RESULTS: Overall, 78.9% (438/555) of patients completed week 104 of the study. Over 2 years, minimal changes were observed in total radiographic SI joint scores (mean [SD] change, - 0.04 [0.49] and 0.04 [0.36]) and mSASSS scores (0.04 [0.47] and 0.07 [0.36]) in the secukinumab and placebo-secukinumab groups. Most of the patients showed no structural progression (increase ≤ smallest detectable change) in SI joint score (87.7% and 85.6%) and mSASSS score (97.5% and 97.1%) in the secukinumab and placebo-secukinumab groups. Only 3.3% (n = 7) and 2.9% (n = 3) of patients in the secukinumab and placebo-secukinumab groups, respectively, who were mNY-negative at baseline were scored as mNY-positive at week 104. Overall, 1.7% and 3.4% of patients with no syndesmophytes at baseline in the secukinumab and placebo-secukinumab group, respectively, developed ≥ 1 new syndesmophyte over 2 years. Reduction in SI joint BME observed at week 16 with secukinumab (mean [SD], - 1.23 [2.81] vs - 0.37 [1.90] with placebo) was sustained through week 104 (- 1.73 [3.49]). Spinal inflammation on MRI was low at baseline (mean score, 0.82 and 1.07 in the secukinumab and placebo groups, respectively) and remained low (mean score, 0.56 at week 104). CONCLUSION: Structural damage was low at baseline and most patients showed no radiographic progression in SI joints and spine over 2 years in the secukinumab and placebo-secukinumab groups. Secukinumab reduced SI joint inflammation, which was sustained over 2 years. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02696031.

Clinimetric Validation of the Assessment of Spondyloarthritis International Society Health Index in Patients With Radiographic Axial Spondyloarthritis in Ixekizumab Trials.

OBJECTIVE: To assess test-retest reliability, construct validity, known groups discrimination, and responsiveness of the Assessment of the SpondyloArthritis international Society Health Index (ASAS HI) to evaluate functioning, disability, and health in patients with radiographic axial spondyloarthritis (r-axSpA). METHODS: Data were generated from 2 randomized, placebo-controlled, active-controlled phase III ixekizumab studies (COAST-V, N = 341; COAST-W, N = 316). Assessments included the following: test-retest reliability (ie, intraclass correlation coefficients [ICCs] between ASAS HI scores at screening and baseline), construct validity (ie, Spearman correlation with standard r-axSpA outcome measures), known groups discrimination (ie, 1-way ANOVA comparing the ASAS HI with different disease activity categories, measured by the Ankylosing Spondylitis Disease Activity Score [ASDAS]), and responsiveness (ie, Spearman correlation between changes in the ASAS HI and changes in the Bath Ankylosing Spondylitis Functional Index [BASFI], the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], the ASDAS, and the Patient Global Assessment [PtGA] as well as ANOVA comparing changes in the ASAS HI with various responder categories). RESULTS: The ICC for test-retest reliability was 0.78 for COAST-V and 0.76 for COAST-W, indicating adequate agreement. Moderate-to-large correlations (r = 0.40-0.61) were observed between the ASAS HI and the BASDAI. Statistically significant differences (all P < 0.001) between mean ASAS HI scores were observed for subgroups based on ASDAS-defined disease activity categories at baseline and week 16. Moderate-to-large correlations existed between changes in the ASAS HI and the BASFI, BASDAI, ASDAS, and PtGA from baseline to week 16. The ASAS HI differentiated statistically (P < 0.001) between ASAS, BASDAI, and ASDAS response groups. CONCLUSION: The ASAS HI demonstrated reliability, construct validity, known groups discrimination, and responsiveness in adults with r-axSpA in 2 clinical trials.

A simple point-of-care assay accurately detects anti-spike antibodies after SARS-CoV-2 vaccination.

Objective: Lateral flow assays (LFA) are sensitive for detecting antibodies to SARS-CoV-2 proteins within weeks after infection. This study tested samples from immunocompetent adults, and those receiving treatments for chronic inflammatory diseases (CID), before and after mRNA SARS-CoV-2 vaccination. Methods: We compared results obtained with the COVIBLOCK Covid-19 LFA to those obtained by anti-spike (S) ELISA. Results: The LFA detected anti-S antibodies in 29 of 29 (100%) of the immunocompetent and 110 of 126 (87.3%) of the CID participants after vaccination. Semiquantitative LFA scores were statistically significantly lower in samples from immunosuppressed participants, and were significantly correlated with anti-S antibody levels measured by ELISA. Conclusions: This simple LFA test is a practical alternative to laboratory-based assays for detecting anti-S antibodies after infection or vaccination. This type of test may be most useful for testing people in outpatient or resource-limited settings.

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials.

OBJECTIVES: Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum. METHODS: In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24. RESULTS: 254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low. CONCLUSIONS: Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.

The faecal microbiota is distinct in HLA-B27+ ankylosing spondylitis patients versus HLA-B27+ healthy controls.

OBJECTIVES: Spondyloarthritis (SpA) results from the interplay between genetic and environmental factors. An emerging modifiable factor is the human intestinal microbiota, which multiple studies in children and adults have shown to be abnormal in SpA patients, including enthesitis related arthritis and ankylosing spondylitis (AS). However, HLA-B27 itself appears to impact the contents of the microbiota and is more common in SpA patients versus controls, thus serving as a confounding factor in most comparative studies. METHODS: This was a cross-sectional study that evaluated the contents of the faecal microbiota among 29 patients with HLA-B27+ AS and 43 healthy adults who underwent 16S sequencing and genotyping as part of the TwinsUK Programme. RESULTS: HLA-B27 positive+ patients and healthy controls demonstrated substantial clustering based upon diagnosis. Decreased richness was observed among the AS patients, although measures of evenness were similar. After correction for multiple comparisons, several taxa - including Faecalibacterium prausnitzii and Coprococcus - were elevated in AS patients compared to controls, even when restricted to female subjects, while Bacteroides fragilis, Ruminococcus, and Akkermansia muciniphila were depleted in AS patients. CONCLUSIONS: Consistent with some previous studies, our study demonstrates in patients with AS associations with Coprococcus, Bacteroides, and Ruminococcus. Other findings, including increased Faecalibacterium, are inconsistent with previous studies and thus potentially underscore the necessity of evaluating HLA-B27 positive controls in studies evaluating the impact of the intestinal microbiota on SpA.

Sleep Disturbance and SARS-CoV-2 Vaccinations in Patients With Chronic Inflammatory Disease.

OBJECTIVE: Immunocompromised patients with chronic inflammatory disease (CID) may have experienced additional psychosocial burden during the COVID-19 pandemic due to their immunocompromised status. This study was undertaken to determine if vaccination would result in improved patient-reported outcomes longitudinally among individuals with CID undergoing SARS-CoV-2 vaccination regardless of baseline anxiety. METHODS: Data are from a cohort of individuals with CID from 2 sites who underwent SARS-CoV-2 vaccination. Participants completed 3 study visits before and after 2 messenger RNA vaccine doses in the initial vaccination series when clinical data were collected. Patient-reported outcomes were measured using the Patient-Reported Outcomes Measurement Information System 29-item Health Profile and expressed as T scores, with 2 groups stratified by high and low baseline anxiety. Mixed-effects models were used to examine longitudinal changes, adjusting for age, sex, and study site. RESULTS: A total of 72% of the cohort was female with a mean ± SD age of 48.1 ± 15.5 years. Overall, sleep disturbance improved following both doses of SARS-CoV-2 vaccinations, and anxiety decreased after the second dose. Physical function scores worsened but did not meet the minimally important difference threshold. When stratifying by baseline anxiety, improvement in anxiety, fatigue, and social participation were greater in the high anxiety group. Physical function worsened slightly in both groups, and sleep disturbance improved significantly in the high anxiety group. CONCLUSION: Sleep disturbance decreased in a significant and meaningful way in patients with CID upon vaccination. In patients with higher baseline anxiety, social participation increased, and anxiety, fatigue, and sleep disturbance decreased. Overall, results suggest that SARS-CoV-2 vaccination may improve mental health and well-being, particularly among those with greater anxiety.

Virtually Speaking: The Impact of a Nationwide Synchronous and Asynchronous Learning Forum.

OBJECTIVE: To address significant disruptions in didactic education precipitated by the COVID-19 pandemic, a group of rheumatology program directors collaborated with the American College of Rheumatology to create a virtual fellows-in-training (V-FIT) program. METHODS: A working group was composed to develop the virtual didactic program comprising live virtual sessions of core curricular rheumatology topics that were recorded to permit asynchronous learning. Nationally recognized educators were invited to lead sessions to fill the void in didactic education occurring on a broad scale across US rheumatology fellowship training programs. Demographic information, live and asynchronous participation data, and feedback surveys were collected from participants in the program. RESULTS: There were 3 components to V-FIT: the Virtual Rheumatology Learning (ViRL) series, the Virtual Rheumatology Practicum (ViP), and the Virtual Rheumatology Teaching Lessons (ViTLs). The ViRL program had global impact with more than 2,000 learners from more than 55 countries. ViP provided a standardized curriculum of rheumatology topics for incoming first-year fellows. ViTLs addressed advanced and interdisciplinary rheumatic disease topics for learners at all stages. CONCLUSION: With collaboration, adaptation, and innovation, the V-FIT program not only maintained but also enhanced education for rheumatology trainees, was enriched by national and international participation, and provided standardized, broadly accessible content with interdisciplinary learning.

Why Do Some Patients Have Severe Sacroiliac Disease But No Syndesmophytes in Ankylosing Spondylitis? Data From a Nested Case-Control Study.

OBJECTIVE: Sacroiliac (SI) joint and spinal inflammation are characteristic of ankylosing spondylitis (AS), but some patients with AS have been identified who have discordant radiographic disease. We studied an AS subgroup with long-standing disease and fused SI joints. We identified factors associated with discrepant degrees of radiographic damage between the SI joints and spine. METHODS: From the Prospective Study of Outcomes in AS (PSOAS) cohort, patients with a disease duration ≥ 20 years and fused SI joints were included in a nested case-control design. Patients with and without syndesmophytes were used as cases and controls for analysis. We used classification and regression tree (CART) analysis to determine risk factors for syndesmophytes presence and reexamined the validity of the risk factors using univariable logistic regression models. RESULTS: There were 354 patients in the subgroup, 23 of whom lacked syndesmophytes. CART analysis showed females were less likely to have syndesmophytes. The next important predictor was age of symptom onset in males, with age of onset ≤ 16 years being less likely to have syndesmophytes. Univariable analysis confirmed females were less likely to have syndesmophytes (odds ratio [OR] 0.17, 95% CI 0.07-0.41). Syndesmophyte presence was associated with HLA-B27 positivity (P = 0.03) and age of symptom onset > 16 years old (OR 2.72, 95% CI 1.15-6.45). All 23 patients who lacked syndesmophytes were HLA-B27 positive. CONCLUSION: Using CART analysis and univariable modeling, women were less likely to have syndesmophytes despite advanced disease duration and SI joint disease. Patients with younger age of symptom onset were less likely to have syndesmophytes. All patients without syndesmophytes were HLA-B27 positive, indicating HLA-B27 positivity may be more associated with SI disease than spinal disease.