The Burden of Spine Structural Damage on Function in Patients With Axial Spondyloarthritis: Adaptation-Mediated Uncoupling?

OBJECTIVE: To investigate the association between spinal damage and functional capacity in patients with axial spondyloarthritis (axSpA) and to compare the performance of 2 radiographic scores (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] and Combined Ankylosing Spondylitis Spine Score [CASSS]). METHODS: Radiographs from 101 patients with axSpA were scored for cervical facet joints (CFJ) and mSASSS for vertebral bodies. CASSS was calculated as the sum of both scores. Physical function was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI); disease activity by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS); mobility by Bath Ankylosing Spondylitis Metrology Index (BASMI); and quality of life by Ankylosing Spondylitis Quality of Life (ASQOL). Univariate and multivariate analyses were performed to investigate the association between possible explanatory variables and outcomes. RESULTS: BASFI correlated strongly with ASQOL (Spearman ρ 0.66) and BASDAI (ρ 0.70), moderately with BASMI (ρ 0.46) and ASDAS (ρ 0.59), and weakly with mSASSS (ρ 0.29) and CASSS (ρ 0.28). A best-fit multivariate model for BASFI, adjusted for symptom duration, age, sex, and smoking status, included BASDAI (B 0.76, P < 0.001), BASMI (B 0.62, P < 0.001), and history of total hip arthroplasty (B 1.22, P = 0.05). Radiographic scores were predictors of BASFI only when BASMI was removed from the model (mSASSS: B 0.03, P = 0.01; CASSS: B 0.02, P = 0.01). CONCLUSION: Spinal damage was independently associated with physical function in axSpA, but to a lesser extent than disease activity and mobility. Moreover, incorporating CFJ assessment in the mSASSS did not improve the ability to predict function.

Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry.

OBJECTIVE: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. METHODS: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. RESULTS: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. CONCLUSION: No significant differences were found between treatments in long-term survival due to inefficacy or AEs.

Factors Associated With Treatment Pathways in Early Axial Spondyloarthritis: A Multistate Analysis of the 10-Year Follow-Up of the DESIR Cohort.

OBJECTIVE: Current recommendations for the management of patients with axial spondyloarthritis (axSpA) emphasize the need of an individualized strategy in therapeutic decision-making. The study objectives were to describe therapeutic strategies observed in axSpA, and to assess the factors associated with treatment intensification over time. METHODS: We included patients with axSpA from the French prospective cohort DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes), with a scheduled 10-year follow-up. A multistate model with 4 ordered treatment states (no treatment, nonsteroidal antiinflammatory drugs [NSAIDs], conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], and tumor necrosis factor inhibitors [TNFi]) was defined, with 6 possible transitions. Restricted mean sojourn times in each state were estimated. Then, predictors of those transitions were assessed by multivariable Cox models. RESULTS: A total of 686/708 (96.9%) patients who had > 1 visit were analyzed. At cohort entry, 199 (29%) were untreated, 427 (62.2%) were receiving NSAIDs, 60 (8.7%) csDMARDs, and none were receiving TNFi. Over the follow-up period, patients mostly (46.4% of the time) received NSAIDs, followed by TNFi (24.4% of the time). The presence of sacroiliitis on radiographs, inflammatory bowel disease, and articular index were jointly associated with the transition to NSAIDs. Longer duration in the previous state often decreased the hazard of the transition to csDMARDs or TNFi. Worse disease activity outcomes increased the hazard of most transitions. CONCLUSION: To our knowledge, this was the first study using a multistate model to easily represent different treatment states, detailing the transitions across them and their associated factors. Different time profiles for the management of patients with axSpA were identified, including in those abstaining from treatment up to a significant proportion of patients treated with csDMARDs.

Association of Infant Breastfeeding and Juvenile Spondyloarthritis: A Case-Control Study.

OBJECTIVE: Given the multifactorial pathogenesis of juvenile spondyloarthritis (JSpA) and evidence of a protective effect in phenotypically similar diseases, we aimed to test whether breastfeeding is associated with the development and disease activity of JSpA. METHODS: This single-center retrospective case-control study included children with JSpA and age- and sex-matched controls with a 1:1 ratio. Univariable and multivariable conditional logistic regression modeling for matched pairs was used to test the association of infant factors with the development of JSpA, including infant nutrition and form of delivery. Linear regression was used to assess the association of JSpA disease activity (JSpA Disease Activity Index with 6 elements [JSpADA6]) at presentation with breastfeeding exposure, form of delivery, and antibiotic exposure. RESULTS: For the 195 case-control matched pairs, the mean age was 13.0 years and 47.7% were female. For breastfeeding, 88.7% of controls and 69.2% of JSpA cases were exposed to breastfeeding of any duration, respectively (P < 0.001). In the multivariable model, exclusive breastfeeding > 6 months was independently and significantly associated with a lower chance of JSpA development (odds ratio 0.47, 95% CI 0.30-0.72; P < 0.001). The median JSpADA6 was not significantly associated with breastfeeding for > 6 months. However, vaginal delivery was significantly associated with a lower JSpADA6 (B = -0.65, 95% CI -1.13 to -0.17; P = 0.008). CONCLUSION: This study suggests that infant factors that affect the microbiome may be associated with the occurrence and disease activity of JSpA at presentation.

Macrophage Activation Syndrome in the Setting of Rheumatic Diseases.

Patients with established rheumatic disorders may develop complications of macrophage activation syndrome due to severe flares of the underlying disease (adult-onset Still's disease, SLE); however, in most other rheumatic disorders, MAS develops in association with identified viral or other infectious triggers. It is therefore important to pursue appropriate studies to identify potential infectious triggers in rheumatic disease patients who develop MAS. Management is best directed toward treatment of the triggering infections and combinations of high-dose corticosteroids, calcineurin inhibitors, and biologic therapies targeting IL-1 and/or IL-6 to suppress the associated cytokine storm.

Immune checkpoint inhibitor-induced inflammatory arthritis as a model of autoimmune arthritis.

The development of inflammatory arthritis in patients receiving immune checkpoint inhibitor therapy is increasingly recognized due to the growing use of these drugs for the treatment of cancer. This represents an important opportunity not only to define the mechanisms responsible for the development of this immune-related adverse event and to ultimately predict or prevent its development, but also to provide a unique window into early events in the development of inflammatory arthritis. Knowledge gained through the study of this patient population, for which the inciting event is known, could shed light into the pathogenesis of autoimmune arthritis. This review will highlight the clinical and immunologic features of these entities to define common elements for future study.

Predictors of long-term functional outcomes of juvenile idiopathic arthritis-enthesitis-related arthritis: a single centre experience.

OBJECTIVES: Long-term functional outcomes in enthesitis-related arthritis (ERA) is limited from developing countries. We assessed the clinical and genetic factors that predicted the long-term functional outcome in ERA. METHODS: Patients with ERA having ≥5 years of disease and >16 years of age were included in this cross-sectional study. Data on clinical features within 6 months of disease onset was collected from hospital records. Bath indices, HAQ Disability Index (HAQ-DI) and World Health Organization's Quality of Life (WHO-QOL) were assessed at last visit. Poor functional outcome (PFO) was defined as BASFI > 1.5 or HAQ-DI > 1. Persistent disease activity (PDA) was defined as BASDAI ≥ 4. Endoplasmic reticulum aminopeptidase 1 (ERAP1) and IL-23 receptor single nucleotide polymorphism genotyping was performed with the TaqMan method and HLA-B27 by PCR. RESULTS: One hundred and eighty-one patients [170 male, median (interquartile range) age of disease onset 12.5 (10-15) years, disease duration 7 (5-11) years] were recruited. There was a delay in diagnosis of 3 (1-5) years. The median Ankylosing Spondylitis Disease Activity Score (ASDAS)-ESR, BASDAI, HAQ-DI and BASFI at inclusion were 2.6 (1.8-3.6), 2.6 (1-5.2), 0.5 (0-0.5) and 1.6 (0.3-3.2), respectively. BASFI and HAQ-DI correlated with ASDAS-ESR, ASDAS-CRP and WHO-QOL-BREF. Those with PFO (n = 98) had a longer delay in diagnosis (4 vs 2 years, P < 0.001), lower prevalence of arthritis at onset [odds ratio (OR) = 0.3; 95% CI: 0.1, 0.8], higher prevalence of ERAP1 (rs27044) allele C (OR = 7.2; 95% CI: 1.5, 33.7) and higher disease activity currently. Delay in diagnosis (OR = 1.2; 95% CI: 1.08, 1.4) was the sole predictor of PFO in multivariate analysis. One-third of patients had PDA. Tarsitis at disease onset was the sole predictor of PDA (OR = 2.3; 95% CI: 1.009, 5.4). CONCLUSIONS: PFO was seen in one-half of JIA-ERA in the long-term and was associated with active disease with delay in diagnosis as its sole predictor.

The prevalence and impact of polypharmacy in rheumatology.

Polypharmacy is increasingly common in rheumatology due to the complex nature of managing chronic autoimmune diseases. To date there has been limited research into the impact of polypharmacy on rheumatology patients. In this article we reviewed the literature to characterize the prevalence of polypharmacy and its effect on patients. In addition, we have highlighted some key drug-drug interactions to consider involving DMARDs as well as complementary and alternative medicines. There is emerging evidence demonstrating that polypharmacy contributes to adverse outcomes and alters treatment response. This association is best described in RA and is less clear in other patient cohorts. It is also unclear whether polypharmacy is directly harmful or just a surrogate marker for other factors affecting outcomes. Rheumatologists should be aware of the risk of polypharmacy as well as specific drug-drug interactions that can occur in managing chronic autoimmune disease.

Modified Juvenile Spondyloarthritis Disease Activity Index in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.

OBJECTIVE: To validate the Juvenile Spondyloarthritis Disease Activity Index (JSpADA), and modified versions thereof, in a North American cohort of patients with enthesitis-related arthritis (ERA). METHODS: We utilized the Childhood Arthritis and Rheumatology Research Alliance Registry database ERA cohort to validate the JSpADA and its modifications (JSpADA6-no Schober, no C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR]; JSpADA7-no Schober; and JSpADA7-no CRP/ESR) using the Outcome Measures in Rheumatology principles of face validity, discriminative validity, and responsiveness to change. RESULTS: There were 51 subjects (64 visits) with complete JSpADA data with a mean age of 13.7 years and disease duration of 30.9 months. Subjects were predominantly White (84.3%), and 56.9% were male and 50% were HLA-B27 positive. The JSpADA showed high correlation with the clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10; r = 0.81), moderate-to-high correlation with physician global assessment (PGA; r = 0.69), and low-to-fair correlation with Childhood Health Assessment Questionnaire (CHAQ; r = 0.22). The modifications of the JSpADA (JSpADA7-no Schober; JSpADA7-no CRP/ESR; and JSpADA6-no Schober, no CRP/ESR) performed similarly with high correlation with cJADAS10 (r = 0.81, 0.79, and 0.80, respectively), moderate-to-high correlation with PGA (r = 0.65, 0.67, 0.64, respectively), and low-to-fair correlation with CHAQ (r = 0.35, 0.34, 0.39, respectively). All modified versions of JSpADA had good responsiveness to change. All versions of JSpADA had excellent discriminative validity. CONCLUSION: We propose the term modified JSpADA for the modification of JSpADA with 6 elements (JSpADA6-no Schober, no CRP/ESR). This shorter disease activity index may improve implementation of JSpADA in both clinical practice and research trials.

When MRI would be useful in patients without evidence of sacroiliitis on radiographs?

We aimed to identify when magnetic resonance imaging (MRI) would be useful to diagnose patients with suspected axial spondyloarthropathy (AxSpA) without evidence of sacroiliitis on radiographs. We retrospectively reviewed electronic medical records of patients who underwent pelvis MRI after radiographs at the rheumatology clinic in a single tertiary center in Korea. Patients underwent imaging from January 2020 to July 2022. We collected data including complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen (HLA)-B27, history of acute anterior uveitis (AAU), peripheral arthritis, dactylitis, inflammatory bowel disease (IBD), enthesopathy, and psoriasis. A total of 105 patients who showed no evidence of sacroiliitis on radiographs were included. The median age of patients was 41.0 years, and 44.8% were male. Of them, 34 showed sacroiliitis on MRI (group 1), and 71 showed no evidence of sacroiliitis even on MRI (group 2). Known AxSpA-related clinical features including AAU, peripheral arthritis, dactylitis, IBD, enthesopathy, and psoriasis were not different between the two groups. HLA-B27 positivity (79.4% vs. 40.0%, p < 0.001), median white blood cell count (7700 vs. 6300, p = 0.007), mean platelet count (307.7 ± 69.7 vs. 265.3 ± 68.9 × 103/µL, p = 0.005), and median CRP level (0.38 vs. 0.10, p = 0.001) showed significant differences between the two groups. In a multivariate analysis, HLA-B27 positivity and platelet count were significantly associated with sacroiliitis on MRI. In our cohort, sacroiliitis was observed on MRI in one-third of patients without radiographic evidence. MRI could be recommended to evaluate sacroiliitis in patients with positive HLA-B27 and a high platelet count.