Comparing symptoms, treatment patterns, and quality of life of ankylosing spondylitis and non-radiographic axial spondyloarthritis patients in the USA: findings from a patient and rheumatologist Survey

Hunter, Theresa; Sandoval, David; Booth, Nicola; Holdsworth, Elizabeth; Deodhar, Atul

doi:10.1007/s10067-021-05642-6

Cited by 20 publications

(15 citation statements)

References 30 publications

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“…Diagnosis can often be a challenge in non-radiographic axial spondyloarthritis (nr-axSpA); the presence of sacroiliitis on magnetic resonance imaging (MRI), human leukocyte antigen (HLA)-B27 and acute phase reactants such as serum C-reactive protein (CRP) remain the most reliable diagnostic tests but with limited specificity and/or sensitivity [ 1 – 3 ]. Patients with nr-axSpA are less likely to be treated with a biologic than patients with radiographic (r)-axSpA (also known as ankylosing spondylitis), despite a similar burden of disease on quality of life [ 4 ]. This may be due to the barriers associated with nr-axSpA diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol

Maksymowych

Kumke

Auteri³

et al. 2021

Arthritis Res Ther

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Background Identification of predictive clinical factors of long-term treatment response may contribute to improved management of non-radiographic axSpA (nr-axSpA) patients. This analysis aims to identify whether any baseline characteristics or Week 12 clinical outcomes in nr-axSpA patients with elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) enrolled in the C-axSpAnd study are predictive of achieving clinical response after 1 year of certolizumab pegol (CZP). Methods C-axSpAnd (NCT02552212) was a phase 3, multicentre study, including a 52-Week double-blind, placebo-controlled period. Enrolled patients were randomised to CZP 200 mg Q2W or placebo. Predictors of Week 12 (CZP group only) and Week 52 clinical response were identified using a multivariate stepwise logistic regression analysis. Response variables included Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI), Assessment of SpondyloArthritis International Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index 50% response (BASDAI50) and ASDAS inactive disease (ASDAS-ID). Predictive factors assessed included demographic and baseline characteristics and clinical outcomes at Week 12. A p-value <0.05 was required for forward selection into the model and p ≥0.1 for backward elimination. Missing data or values collected after switching to open-label treatment were accounted for using non-responder imputation. Sensitivity analyses accounted for patients with changes in non-biologic background medication. Results Of 317 enrolled patients, 159 and 158 were randomised to CZP and placebo, respectively. Younger age and male sex were identified as predictors of Week 12 response across all assessed efficacy outcomes in CZP-treated patients. Consistent predictors of Week 52 response, measured by ASDAS-MI, ASAS40 and BASDAI50, included human leukocyte antigen (HLA)-B27 positivity and sacroiliitis on MRI at baseline. MRI positivity was also predictive of achieving ASDAS-ID at Week 52. Sensitivity analyses were generally consistent with the primary analysis. In placebo-treated patients, no meaningful predictors of Week 52 response were identified. Conclusions In this 52-Week, placebo-controlled study in nr-axSpA patients with elevated CRP and/or active sacroiliitis on MRI at baseline, MRI sacroiliitis and HLA-B27 positivity, but not elevated CRP or responses at Week 12, were predictive of long-term clinical response to CZP. Findings may support rheumatologists to identify patients suitable for TNFi treatment. Trial registration ClinicalTrials.gov, NCT02552212. Registered on 15 September 2015

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Section: Introductionmentioning

confidence: 99%

Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol

Maksymowych

Kumke

Auteri³

et al. 2021

Arthritis Res Ther

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“…We compared the divided clusters with radiographic classification and grouping according to HLA-B27 positivity. Various demographic and clinical differences have been reported between patients with radiographic and non-radiographic axial SpA [ 33 , 34 ] and between HLA-B27-positive and HLA-B27-negative patients [ 35 ]. We divided our cohort according to radiographic classifications and HLA-B27 positivity and compared these divisions with the two clusters.…”

Section: Discussionmentioning

confidence: 99%

A cluster analysis of patients with axial spondyloarthritis using tumour necrosis factor alpha inhibitors based on clinical characteristics

et al. 2021

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Background This study aimed to classify the distinct group of patients with axial spondyloarthritis (SpA) on tumour necrosis factor alpha inhibitors (TNFi) according to the baseline characteristics using a clustering algorithm. Methods The clinical characteristics and demographic data of patients with axial SpA included in the Korean College of Rheumatology Biologics and Targeted Therapy registry were investigated. The patterns of disease manifestations were examined using divisive hierarchical cluster analysis. After clustering, we compared the clinical characteristics of patients and the drug survival of TNFi between the classified groups. Results A total of 1042 patients were analysed. The cluster analysis classified patients into two groups: axial group predominantly showing isolated axial manifestations (n = 828) and extra-axial group more frequently showing extra-axial symptoms (n = 214). Almost all extra-axial symptoms (peripheral arthritis, enthesitis, uveitis, and psoriasis) were more frequently observed in the extra-axial group than in the axial group. Moreover, patients in the extra-axial group had shorter disease duration, later disease onset, and higher disease activity than those in the axial group. The disease activity was comparable between the two groups after 1 year of treatment with TNFi. Interestingly, the extra-axial group had a lower drug survival with TNFi than the axial group (p = 0.001). Conclusions Cluster analysis of patients with axial SpA using TNFi classified two distinct clinical phenotypes. These clusters had different TNFi drug survival, clinical characteristics, and disease activity.

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“…Spondyloarthritis (SpA) is a family of chronic inflammatory arthritides primarily targeting the joint entheses, the site of tendon or ligament insertion into bone. Enthesial inflammation can cause pain, joint damage, and loss of mobility in affected sites, leading to significant loss of quality of life ( 1 , 2 ). While in recent years there have been significant advances in the treatment of SpA, headlined by biologic treatments aimed at the blockade of tumor necrosis factor (TNF) and interleukin (IL)-17 ( 3 ); however these treatments are efficacious in only ~60% of patients ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…While in recent years there have been significant advances in the treatment of SpA, headlined by biologic treatments aimed at the blockade of tumor necrosis factor (TNF) and interleukin (IL)-17 ( 3 ); however these treatments are efficacious in only ~60% of patients ( 4 ). In those patients for whom therapy is effective, ~30% of patients discontinue treatment after 12 months due to cost and treatment-associated adverse reactions ( 2 ). Therefore, additional treatment strategies are needed to reduce the burden of this disease.…”

Section: Introductionmentioning

confidence: 99%

Cytokine competent gut-joint migratory T Cells contribute to inflammation in the joint

et al. 2022

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Although studies have identified the presence of gut-associated cells in the enthesis of joints affected by spondylarthritis (SpA), a direct link through cellular transit between the gut and joint has yet to be formally demonstrated. Using KikGR transgenic mice to label in situ and track cellular trafficking from the distal colon to the joint under inflammatory conditions of both the gut and joint, we demonstrate bona-fide gut-joint trafficking of T cells from the colon epithelium, also called intraepithelial lymphocytes (IELs), to distal sites including joint enthesis, the pathogenic site of SpA. Similar to patients with SpA, colon IELs from the TNFΔARE/+ mouse model of inflammatory bowel disease and SpA display heightened TNF production upon stimulation. Using ex vivo stimulation of photo-labeled gut-joint trafficked T cells from the popliteal lymph nodes of KikGR and KikGR TNFΔARE/+ we saw that the CD4+ photo-labeled population was highly enriched for IL-17 competence in healthy as well as arthritic mice, however in the TNFΔARE/+ mice these cells were additionally enriched for TNF. Using transfer of magnetically isolated IELs from TNF+/+ and TNFΔARE/+ donors into Rag1-/- hosts, we confirmed that IELs can exacerbate inflammatory processes in the joint. Finally, we blocked IEL recruitment to the colon epithelium using broad spectrum antibiotics in TNFΔARE/+ mice. Antibiotic-treated mice had reduced gut-joint IEL migration, contained fewer Il-17A and TNF competent CD4+ T cells, and lessened joint pathology compared to untreated littermate controls. Together these results demonstrate that pro-inflammatory colon-derived IELs can exacerbate inflammatory responses in the joint through systemic trafficking, and that interference with this process through gut-targeted approaches has therapeutic potential in SpA.

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Comparing symptoms, treatment patterns, and quality of life of ankylosing spondylitis and non-radiographic axial spondyloarthritis patients in the USA: findings from a patient and rheumatologist Survey

Cited by 20 publications

References 30 publications

Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol

Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol

A cluster analysis of patients with axial spondyloarthritis using tumour necrosis factor alpha inhibitors based on clinical characteristics

Cytokine competent gut-joint migratory T Cells contribute to inflammation in the joint

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