Association of clinical response criteria and disease activity levels with axial spondyloarthritis core domains: results from two phase 3 randomised studies, BE MOBILE 1 and 2.

OBJECTIVE: To assess how achievement of increasingly stringent clinical response criteria and disease activity states at week 52 translate into changes in core domains in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA). METHODS: Patients in BE MOBILE 1 and 2 achieving different levels of response or disease activity (Assessment of SpondyloArthritis International Society (ASAS) and Ankylosing Spondylitis Disease Activity Score (ASDAS) response criteria, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50)) at week 52 were pooled, regardless of treatment arm. Associations between achievement of these endpoints and change from baseline (CfB) in patient-reported outcomes (PROs) measuring core axSpA domains, including pain, fatigue, physical function, overall functioning and health, and work and employment, were assessed. RESULTS: Achievement of increasingly stringent clinical efficacy endpoints at week 52 was generally associated with sequentially greater improvements from baseline in all PROs. Patients with nr-axSpA achieving ASAS40 demonstrated greater improvements (CfB) than patients who did not achieve ASAS40 but did achieve ASAS20, in total spinal pain (-5.3 vs -2.8, respectively), Functional Assessment of Chronic Illness-Fatigue subscale (12.7 vs 6.7), Bath Ankylosing Spondylitis Function Index (-3.9 vs -1.8), European Quality of Life 5-Dimension 3-Level Version (0.30 vs 0.16), Work Productivity and Activity Impairment-axSpA presenteeism (-35.4 vs -15.9), overall work impairment (-36.5 vs -12.9), activity impairment (-39.0 vs -21.0) and sleep (9.0 vs 3.9). Results were similar for ASDAS and BASDAI50. Similar amplitudes of improvement were observed between patients with nr-axSpA and r-axSpA. CONCLUSIONS: Patients treated with bimekizumab across the full axSpA disease spectrum, who achieved increasingly stringent clinical response criteria and lower disease activity at week 52, reported larger improvements in core axSpA domains.

IL-17-producing cells in ankylosing spondylitis patients show gender-based differences in gene expression.

OBJECTIVES: Gender has been shown to impact disease expression in ankylosing spondylitis (AS) and Th17 cells play a key role in AS pathogenesis. To better understand what Th17-associated immune pathways are different between men and women, we compared the transcriptome of IL-17-enriched peripheral blood mononuclear cells (PBMCs) in male and female AS patients, with a particular focus on inflammatory cytokine genes. METHODS: PBMCs were collected from 10 female and 11 male AS patients at the Clinical Research Unit of MetroHealth Medical Center. IL-17-enriched PBMCs were isolated and stimulated with CytoStim. RNA-sequencing (RNA-seq) was performed on the samples, and the data were analysed using iPathwayGuide. Inflammatory markers and genes related to Th17 differentiation and function were identified based on previous studies. RESULTS: RNA-seq identified 12,893 genes with 2,851 genes with p-values <0.05 with distinct patterns of gene expression between male and female AS patients. TGF-ß, PGE2, and S100 proteins were significantly upregulated in males. Levels of IL-12B, a Th17 inducer, were lower in males compared to females. Additionally, receptors of IL-6, 12, 23, TGF-ß, and PGE2 were downregulated in males, except for IL-17RC, which was upregulated. Genes involved in Th17 differentiation showed differential expression between genders, with elevated expression of BATF, SOCS1, NKD2, and ARID5A in men and decreased expression of FOXO1. CONCLUSIONS: Transcriptomic analysis revealed that male AS patients exhibit distinct expression patterns of IL-17 pro-inflammatory genes, which may contribute to the phenotypic differences observed between genders in AS.

Dose Tapering and Discontinuation of Biologic DMARDs in Axial Spondyloarthritis: A Narrative Review (2023 SPARTAN Annual Meeting Proceedings).

PURPOSE OF REVIEW: Limited data is available for tapering or discontinuation of biologic therapy in patients with axSpA who are in disease remission. The current review concentrates on published studies regarding dose tapering or withdrawal of biologics in axSpA. RECENT FINDINGS: Recent evidence in light of randomized controlled trials suggests that tapering of b-DMARDs is a feasible strategy to maintain remission or low disease activity in axSpA patients. TNF inhibitors were the studied biologics in most of these trials. The disease flare rates were comparable to those maintained on standard dose in most of these studies, although with variable tapering strategies and follow-up. Additionally, the duration of disease in remission prior to tapering, studied primary outcome, and flare definitions were heterogeneous. Female sex, HLA-B*27 negativity, high physician global score, and high CRP were negative predictors of successful tapering, but not consistently reported in all the trials. Although designed to address efficacy, there were no safety concerns with b-DMARD tapering. Withdrawal or complete discontinuation of biologics met with increased risk of flares compared to standard dosing. Tapering of TNF inhibitors may be feasible in certain axSpA patients with an acceptable disease state; however, discontinuation is not currently recommended owing to increased risk of flare. Future studies with axSpA patients with longer remission duration prior to taper and different doses and types of b-DMARDs may provide more guidance.

Thresholds for unacceptable work state in radiographic axial Spondyloarthritis of four presenteeism and two clinical outcome measurement instruments.

OBJECTIVES: To a) identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed r-axSpA patients; b) determine whether those thresholds accurately predict future adverse work outcomes (AWO) (sick leave or short/long-term disability); c) evaluate the performance of traditional health-outcomes for r-axSpA; d) explore whether thresholds are stable across contextual factors. METHODS: Data from the multinational AS-PROSE study was used. Thresholds to determine whether patients consider themselves in an 'unacceptable work state' were calculated at baseline for four instruments assessing presenteeism and two health-outcomes specific for r-axSpA. Different approaches derived from the receiver operating characteristic methodology were used. Validity of the optimal thresholds was tested across contextual factors and for predicting future AWO over 12 months. RESULTS: Of 366 working patients, 15% reported an unacceptable work state; 6% experienced at least one AWO in 12 months. Optimal thresholds were: WPAI-presenteeism ≥40 (AUC 0.85), QQ-method <97 (0.76), WALS ≥0.75 (AUC 0.87), WLQ-25 ≥ 29 (AUC 0.85). BASDAI and BASFI performed similarly to the presenteeism instruments: ≥4.7 (AUC 0.82) and ≥3.5 (AUC 0.79), respectively. Thresholds for WALS and WLQ-25 were stable across contextual factors, while for all other instruments they overestimated unacceptable work state in lower educated persons. Proposed thresholds could also predict future AWO, although with lower performance, especially for QQ-method, BASDAI and BASFI. CONCLUSIONS: Thresholds of measurement instruments for presenteeism and health status to identify unacceptable work state have been established. These thresholds can help in daily clinical practice to provide work related support to r-axSpA patients at risk for AWO.

Disease characteristics, pathogenesis, and treatment controversies of axial psoriatic arthritis.

Axial psoriatic arthritis (axPsA) has considerable overlap with axial spondyloarthritis (axSpA) but has some unique features that sometimes preclude classification into axSpA. It has some clinical and radiographic differences compared to axSpA. Imaging typically shows asymmetric syndesmophytes, mainly in the cervical spine, with less frequent sacroiliitis. It more commonly presents later in life and is associated with less severe inflammatory back pain than axSpA. The interleukin (IL) IL-23/IL-17 axis is central to the pathogenesis of both diseases. However, the response to therapies targeting these cytokines has been different. IL-23 inhibitors are ineffective in axSpA but may be effective in psoriatic arthritis (PsA). Recent post hoc analyses of clinical trial data with IL-23 inhibitors in PsA have raised the possibility of their efficacy in axPsA and need evaluation in future clinical trials. Moreover, there is a need for classification criteria for axPsA and better tools to assess therapeutic response.

Mortality and Ankylosing Spondylitis in the US population: leading causes and associated factors.

OBJECTIVE: Ankylosing Spondylitis (AS) is a chronic inflammatory condition that affects the axial skeleton. Recent studies have shown that mortality risk is higher in AS patients and that it is possibly related to disease activity and duration. Our aim was to investigate the leading causes and factors associated with mortality in hospitalized AS patients in the USA. METHODS: This is a case-control study using the Cerner Health Facts® database between 2015 and 2017. The search was done using ICD codes and administrative claims. Cases were hospitalized AS patients who died during that hospitalization, while controls were patients who survived. In addition to demographics, we collected data on the inpatient use of medications such as NSAIDs, as well as different comorbidities and systemic disease manifestations. The discharge diagnoses for deceased patients were collected to infer causes of mortality. Analysis of association was performed using chi-square tests, t-tests, Wilcoxon rank-sum tests, and logistic regression methods. RESULTS: The leading causes of death were cardiovascular, infectious, respiratory, and traumatic. The Elixhauser comorbidity index was the factor most associated with mortality (p-value < 0.0001), with congestive heart failure and renal disease the most contributing. Drug use disorder was associated with mortality (adjusted OR = 10.9; p = 0.001). Inpatient NSAIDs use was not associated with increased odds for mortality (p-value 0.33). CONCLUSION: Cardiovascular and renal comorbidities are associated with mortality and need to be targeted early on to lower the odds of mortality as patients age. Strategies to prevent opioid and drug abuse should be strengthened in the AS population. Key Points • Cardiovascular and renal comorbidities are associated with mortality and need to be screened for and targeted early on to lower the odds of mortality as patients age. • Drug use disorder including opioid dependence is associated with mortality, and strategies to prevent opioid and drug abuse should be strengthened in the AS population.

Relationships of Work Productivity and Activity Impairment With Patient-Reported Outcomes in Ankylosing Spondylitis: Results From Two Trials.

OBJECTIVE: We examined the relationships of work productivity and activity impairment with key patient-reported outcomes (PROs) assessing pain, disease activity, and health-related quality of life (HRQoL) in patients with ankylosing spondylitis (AS). METHODS: This post hoc analysis pooled available data from baseline to end of the double-blind phase of phase 2 and 3 placebo-controlled tofacitinib trials in patients with active AS. A repeated-measures longitudinal model assessed the relationships (linear or nonlinear) between Work Productivity and Activity Impairment questionnaire in Spondyloarthritis (WPAI:SpA) domains (absenteeism, activity impairment, presenteeism, and productivity loss) as outcomes and key PROs (total back pain, nocturnal spinal pain, Patient Global Assessment of Disease Activity, AS Quality of Life, EuroQol 5-Dimension 3-Level [EQ-5D-3L], and EQ-5D Visual Analog Scale [EQ-5D-VAS]) as predictors. RESULTS: Data from 330 to 475 patients were available, depending on the analysis. Relationships between WPAI:SpA domains and PROs were approximately linear. The worst PRO scores were associated with a decline in patients' work capacity (measured by activity impairment, presenteeism, and productivity loss [>65%]); the best scores were associated with improvements in WPAI:SpA domains (8%-23%). Incremental PRO improvements were associated with improvement of activity impairment, presenteeism, and productivity loss. Relationships between absenteeism and PROs were the weakest, owing to absenteeism being low in the study population. CONCLUSION: Evidence of linear relationships between work productivity and activity impairment with patient-reported pain, disease activity, and HRQoL was observed. Interventions to control pain and disease activity and improve HRQoL are therefore likely to improve work productivity and reduce activity impairment in patients with AS.

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.

2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

OBJECTIVE: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily. METHODS: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.

2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

OBJECTIVE: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily. METHODS: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.

Clinical profile and treatment utilisation based on HLA-B*27 status in axial spondyloarthritis: results from ASAS-PerSpA study.

OBJECTIVE: We aimed to characterize differences of clinical features, extra-musculoskeletal manifestations and treatment utilizations based on the patients' HLA-B*27 status in a global axSpA cohort and identify predictors of HLA-B*27 negativity in these patients. METHODOLOGY: In post-hoc analysis of the ASAS-PerSpA study, patients fulfilling the 2009 ASAS classification criteria for axSpA and typed for HLA-B*27 were included. The patient characteristics cwere compared between the HLA-B*27(+) and HLA-B*27(-) subgroups. Multivariablete logistic regression was conducted to identify predictors of HLA-B*27 negativity. RESULTS: Of 2910 patients with axSpA from 24 countries, 2269 were tested for HLA-B*27 [1753 HLA-B*27(+) and 516 HLA-B*27(-)]. The proportion of males was higher in the HLA-B*27 (+) compared to the HLA-B*27 (-) subgroup (72.1 vs 54.3%). Patient population with HLA-B*27 (+) more often had positive family history for axSpA (29.8 vs 15.3%), and younger age at diagnosis, 31.6 years (SD 10.9) vs 37.7 years (SD 12.1). HLA-B*27 (-) patients had significantly higher peripheral arthritis (47.5 vs 42.1%, p<0.05), psoriasis (19.4 vs 10.2), enthesitis (56.6 vs 49.8%) and IBD (12.8 vs 3.4) (p<0.001). The exposure to csDMARDS in HLA-B*27 (-) patients was higher (61.2 vs 55.0%, p< 0.05). On multivariable analysis, HLA-B*27 (-) status was positively associated with enthesitis, psoriasis and IBD with an OR 1.27 (1.02-1.57), 1.84 (1.36-2.48) and 4.84 (3.23-7.30) respectively, and inversely associated with uveitis, OR 0.37 (0.27-0.50). CONCLUSION: HLA-B*27 (-) axSpA patients had a longer delay in diagnosis, more frequently had peripheral arthritis, enthesitis, IBD, psoriasis, and were more often treated with csDMARDs compared to HLA-B*27 (+) subgroup.

Efficacy and safety of Janus kinase inhibitors in axial spondyloarthritis.

Skin manifestations are common in axial spondyloarthritis (axSpA) and may precede axial involvement. Multidisciplinary management of patients with spondyloarthritis (SpA) is essential. Combined dermatology-rheumatology clinics are established for early recognition of the disease, comorbidities and a comprehensive treatment approach. Treatment options for axSpA are limited because conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids are ineffective for axial symptoms. Janus kinase inhibitors (JAKi) are targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) that decrease transduction signalling to the nucleus, resulting in a reduced inflammatory response. Currently, tofacitinib and upadacitinib are approved for treating axSpA in patients with inadequate response to TNF inhibitors (TNFi). Upadacitinib has shown efficacy in non-radiographic axSpA (nr-axSpA), suggesting that JAKi are efficacious across the spectrum of axSpA. The availability of JAKi has opened more options for patients with active axSpA based on the efficacy data and the ease of administration.

Pain and Inflammation as Mediators of Tofacitinib Treatment Effect on Fatigue in Patients with Ankylosing Spondylitis: A Mediation Analysis.

INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Using mediation modelling, we describe interrelationships between fatigue, pain, morning stiffness, C-reactive protein (CRP) and tofacitinib treatment in patients with AS. METHODS: Data from phase 2 (NCT01786668)/phase 3 (NCT03502616) studies of patients receiving tofacitinib 5 mg twice daily (BID) or placebo were used. Initial models included treatment as the independent binary variable (tofacitinib 5 mg BID versus placebo); fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F; model A] or Bath AS Disease Activity Index [BASDAI] Q1 [model B]) as the dependent variable; and pain (total back pain/nocturnal spinal pain [model A] or pain measured by BASDAI Q2/3 [model B]), morning stiffness (BASDAI Q5/6) and CRP as mediator variables. RESULTS: Pooled data from 370/371 patients were included in models A/B. Initial models demonstrated that tofacitinib treatment affects fatigue mainly indirectly via pain and morning stiffness. As a result, initial models were respecified to exclude direct treatment effect and the indirect effect via CRP. For respecified model A, 44.0% of the indirect effect of tofacitinib treatment on fatigue was mediated via back pain/morning stiffness, 40.0% via morning stiffness alone and 16.0% via back pain alone (all P < 0.05). For respecified model B, 80.8% of the indirect effect of tofacitinib treatment on fatigue was mediated via pain/morning stiffness and 19.2% via pain alone (both P < 0.05). CONCLUSIONS: In tofacitinib-treated patients with AS, improvements in fatigue were collectively mediated through combined treatment effects on morning stiffness and pain.

Human Leukocyte Antigen B27-Negative Axial Spondyloarthritis: What Do We Know?

Axial spondyloarthritis (axSpA) is a chronic, immune-mediated disease characterized by inflammatory axial skeleton involvement and extra-musculoskeletal manifestations. The continuum of axSpA ranges from nonradiographic axSpA (nr-axSpA) to ankylosing spondylitis, also known as radiographic axSpA; the latter is defined by definitive radiographic sacroiliitis. Human leukocyte antigen B27 (HLA-B27) is a genetic marker strongly associated with axSpA; it aids in the diagnosis of axSpA, and its absence leads to delay in diagnosis. For HLA-B27-negative patients, disease pathogenesis is poorly understood, signs and symptoms are frequently underrecognized, and diagnosis and treatment are commonly delayed. The proportion of HLA-B27-negative patients may be higher among non-White patients and those with nr-axSpA, who can face additional diagnostic challenges related to lack of definitive radiographic sacroiliitis. In this narrative review, we discuss the role of HLA-B27 in the diagnosis and pathogenesis of axSpA and highlight various pathways and genes that may be related to axSpA pathogenesis in HLA-B27-negative patients. We also emphasize the need to characterize gut microbial communities in these patients. Adequate understanding of clinical and pathological features underlying HLA-B27-negative patients with axSpA will improve diagnosis, treatment, and outcomes for this complex inflammatory disease.

The International Map of Axial Spondyloarthritis Survey: A US Patient Perspective on Diagnosis and Burden of Disease.

OBJECTIVE: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that causes inflammation in the axial skeleton, resulting in structural damage and disability. We aimed to understand the effect of axSpA on work activity, day-to-day function, mental health, relationships, and quality of life and to examine barriers to early diagnosis. METHODS: A 30-minute quantitative US version of the International Map of Axial Spondyloarthritis survey was administered online to US patients aged 18 years and older with a diagnosis of axSpA who were under the care of a health care provider from July 22 to November 10, 2021. This analysis describes demographics, clinical characteristics, journey to axSpA diagnosis, and disease burden. RESULTS: We surveyed 228 US patients with axSpA. Patients had a mean diagnostic delay of 8.8 years, with a greater delay in women versus men (11.2 vs. 5.2 years), and 64.5% reported being misdiagnosed before receiving an axSpA diagnosis. Most patients (78.9%) had active disease (Bath Ankylosing Spondylitis Disease Activity Index score ≥4), reported psychological distress (57.0%; General Health Questionnaire 12 score ≥3), and experienced a high degree of impairment (81.6%; Assessment of Spondyloarthritis International Society Health Index score ≥6). Overall, 47% of patients had a medium or high limitation in activities of daily living, and 46% were not employed at survey completion. CONCLUSION: The majority of US patients with axSpA had active disease, reported psychological distress, and reported impaired function. US patients experienced a substantial delay in time to diagnosis of axSpA that was twice as long in women versus men.

Responsiveness and Minimum Clinically Important Difference in Patient-Reported Outcome Measures Among Patients With Psoriatic Arthritis: A Prospective Cohort Study.

OBJECTIVE: To determine the responsiveness to therapy and minimum clinically important improvement (MCII) for patient-reported outcome measures in psoriatic arthritis (PsA) and to examine the impact of baseline disease activity on the ability to demonstrate change. METHODS: A longitudinal cohort study was performed within the PsA Research Consortium. Patients completed several patient-reported outcomes, including the Routine Assessment of Patient Index Data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Psoriatic Arthritis Impact of Disease 12-item (PsAID12) questionnaire, and others. The mean change in the scores between visits and standardized response means (SRMs) were calculated. The MCII was calculated as the mean change in score among patients who reported minimal improvement. SRMs and MCIIs were compared among subgroups with moderate to highly active PsA and those with lower disease activity. RESULTS: Among 171 patients, 266 therapy courses were included. The mean ± SD age was 51 ± 13.8 years, 53% were female, and the mean swollen and tender joint counts were 3 and 6, respectively, at baseline. SRMs and MCII for all measures were small to moderate, although greater among those with higher baseline disease activity. BASDAI had the best SRM overall and for less active PsA, and the clinical Disease Activity of PsA (cDAPSA) and PsAID12 were best for those with higher disease activity. CONCLUSION: SRMs and MCII were relatively small in this real-world population, particularly among those with lower disease activity at baseline. BASDAI, cDAPSA, and PsAID12 had good sensitivity to change, but selection for use in trials should consider the baseline disease activity of patients to be enrolled.

Effect of Upadacitinib on Disease Activity, Pain, Fatigue, Function, Health-Related Quality of Life and Work Productivity for Biologic Refractory Ankylosing Spondylitis.

INTRODUCTION: Patients with ankylosing spondylitis (AS) have significant unmet treatment needs, despite advancements in biologic therapies. This study evaluated the impact of upadacitinib on clinically meaningful improvement in patient-reported outcomes (PROs) assessing disease activity, pain, fatigue, function, health-related quality of life (HRQoL), and work productivity in patients with AS with inadequate responses or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR). METHODS: Patients enrolled in the phase 3 SELECT-AXIS 2 AS bDMARD-IR study received blinded once-daily oral upadacitinib 15 mg or placebo for 14 weeks. The percentage of patients achieving improvements ≥ minimum clinically important differences (MCID) at week 14 were compared between treatment groups for disease activity (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI), patient global assessment of disease activity (PtGA), total and nocturnal back pain, fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue, FACIT-F), physical function (Bath Ankylosing Spondylitis Functional Index, BASFI), HRQoL (Assessment of SpondyloArthritis international Society Health Index [ASAS HI], Ankylosing Spondylitis Quality of Life [ASQoL], Short form-36 [SF-36] physical [PCS] and mental [MCS] component summary scores), and work productivity (Work Productivity and Activity Impairment [WPAI] Questionnaire). Mean changes from baseline through week 14 in fatigue and HRQoL were compared between treatment groups. RESULTS: A total of 420 patients with active AS who were bDMARD-IR were included. A higher proportion of patients reported MCIDs at week 14 across all PROs with upadacitinib compared with placebo (nominal p ≤ 0.05). Greater improvements in mean change from baseline through week 14 were reported with upadacitinib compared with placebo across FACIT-F, HRQoL, and WPAI, with improvements differentiated as early as week 1 for ASAS HI, ASQoL and SF-36 PCS and week 4 for SF-36 MCS. CONCLUSIONS: Upadacitinib 15 mg demonstrated rapid and clinically meaningful improvements in disease activity, pain, FACIT-F, function, HRQoL, and WPAI among bDMARD-IR patients with active AS. TRIAL REGISTRY: Clinical Registration number: NCT04169373, SELECT-AXIS 2.

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.

Axial Spondyloarthritis and Diagnostic Challenges: Over-diagnosis, Misdiagnosis, and Under-diagnosis.

PURPOSE OF REVIEW: This article aims to review the challenges in axial spondyloarthritis diagnosis and identify the possible contributing factors. RECENT FINDINGS: The inability to reach an accurate diagnosis in a timely fashion can lead to treatment delays and worse disease outcomes. The lack of validated diagnostic criteria and the misuse of the currently available classification criteria could be contributing. There is also significant inter-reader variability in interpreting images, and the radiologic definitions of axial spondyloarthritis continue to be re-defined to improve their positive predictive value. The role of inflammatory back pain features, serologic biomarkers, genetics, and their diagnostic contribution to axial spondyloarthritis continues to be investigated. There is still a significant amount of delay in the diagnosis of axial spondyloarthritis. Appreciating the factors that contribute to this delay is of utmost importance to close the gap. It is similarly important to recognize other conditions that may present with symptoms that mimic axial spondyloarthritis so that misdiagnosis and wrong treatment can be avoided.