A Mechanically Resilient Soft Hydrogel Improves Drug Delivery for Treating Post-Traumatic Osteoarthritis in Physically Active Joints.

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel's potential for PTOA treatment in active patients.

Diagnosis of Inflammatory Bowel Disease-Associated Peripheral Arthritis: A Systematic Review.

BACKGROUND: Inflammatory bowel disease (IBD)-associated peripheral spondyloarthritis (pSpA) decreases quality of life and remains poorly understood. Given the prevalence of this condition and its negative impact, it is surprising that evidence-based disease definitions and diagnostic strategies are lacking. This systematic review summarizes available data to facilitate development and validation of diagnostics, patient-reported outcomes, and imaging indices specific to this condition. METHODS: A literature search was conducted. Consensus or classification criteria, case series, cross-sectional studies, cohort studies, and randomized controlled trials related to diagnosis were included. RESULTS: A total of 44 studies reporting data on approximately 1500 patients with pSpA were eligible for analysis. Data quality across studies was only graded as fair to good. Due to large heterogeneity, meta-analysis was not possible. The majority of studies incorporated patient-reported outcomes and a physical examination. A total of 13 studies proposed or validated screening tools, consensus, classification, or consensus criteria. A total of 28 studies assessed the role of laboratory tests, none of which were considered sufficiently accurate for use in diagnosis. A total of 17 studies assessed the role of imaging, with the available literature insufficient to fully endorse any imaging modality as a robust diagnostic tool. CONCLUSIONS: This review highlights existing inconsistency and lack of a clear diagnostic approach for IBD-associated pSpA. Given the absence of an evidence-based approach, a combination of existing criteria and physician assessment should be utilized. To address this issue comprehensively, our future efforts will be directed toward pursuit of a multidisciplinary approach aimed at standardizing evaluation and diagnosis of IBD-associated pSpA.

This systematic review highlights the lack of an evidence-based approach to the diagnosis of inflammatory bowel disease­associated peripheral spondyloarthritis and the need to standardize evaluation and diagnosis via multidisciplinary collaboration with development of patient-reported outcomes and imaging indices.

Axial spondyloarthritis guidelines - aiming for maximum impact.

PURPOSE OF REVIEW: This review discusses international clinical practice guidelines (CPGs) for axial spondyloarthritis (axSpA) focusing on methodology, guideline quality, and implementation. RECENT FINDINGS: The Assessment of SpondyloArthritis International Society/European Alliance of Associations for Rheumatology (ASAS/EULAR) and Pan-American League of Associations for Rheumatology (PANLAR) recently published axSpA CPGs and updates of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network (ACR/SAA/SPARTAN) and Asia-Pacific League of Associations for Rheumatology (APLAR) CPGs are expected. GRADE has emerged as the dominant framework for CPG development and has been used by three of the four international axSpA guidelines. Notable differences exist among these guidelines in the way that the recommendations are presented. Two of the four acknowledge the need for implementation strategies, but little detail about this is provided. The few studies that have evaluated the implementation of axSpA CPGs have identified poor adherence to recommendations on physical therapy/exercise and disease activity monitoring. Implementation science has identified many barriers and facilitators affecting guideline uptake, including those related to healthcare professionals and to the guidelines themselves. Creation of a tailored implementation plan simultaneously with the CPG is recommended. SUMMARY: While methodological rigor in the creation of evidence-based recommendations is the focus of CPG development, recommendations must be presented in a user-friendly format that makes them easy to apply. 'Living guidelines' could facilitate keeping content up to date. Implementation is critical for the success of a CPG and should be emphasized in future axSpA guideline updates. Further research is needed to better understand the factors impacting the successful implementation of axSpA CPGs.

Screening Tools for Spondyloarthritis in Patients With Psoriasis, Uveitis, and Inflammatory Bowel Disease: A Scoping Review.

OBJECTIVE: Extramusculoskeletal manifestations of spondyloarthritis (SpA) may precede the development of articular features. Patients seen in ophthalmology, dermatology, and gastroenterology clinics with uveitis, psoriasis, or inflammatory bowel disease (IBD) may have undiagnosed SpA. We set out to identify and evaluate screening tools for SpA in patients with psoriasis, uveitis, and IBD and determine factors that influence the performance of these instruments. METHODS: This scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, and Web of Science were searched from inception to January 2022. RESULTS: We identified 13 screening tools for psoriatic arthritis, 2 SpA screening tools for uveitis, and 3 SpA screening tools for IBD. All screening tools were patient-oriented questionnaires except for the Dublin Uveitis Evaluation Tool, a physician-applied algorithm. The questionnaires varied in length, scoring method, cutoff score, and spectrum of included SpA features. Average completion time was less than five minutes. Across the three patient populations, the sensitivities and specificities of these screening tools were comparable in the primary validation cohorts. Sensitivities and specificities were generally lower in secondary validation studies, with marked variability among cohorts. CONCLUSION: Our results highlight the heterogeneity and limitations of existing SpA screening tools. Although these tools show promise for use within a specific target population, none are generalizable to all patients with extramusculoskeletal manifestations at risk of SpA. Future studies should explore the utility of a generic patient-oriented SpA screening tool that can be applied to patients with psoriasis, uveitis, or IBD; is easy to use and comprehend; and captures all clinical domains of SpA.

Axial Spondyloarthritis Treatment Recommendations and Disease Activity Monitoring in Clinical Practice: Results of an Online Survey.

OBJECTIVE: Clinical practice guidelines are not always followed consistently. To better understand potential barriers to the implementation of treatment recommendations in axial spondyloarthritis and ankylosing spondylitis (axSpA/AS), an online survey was conducted. METHODS: Email invitations were sent to US rheumatology care providers in January 2023. The questionnaire included 20 questions, with an estimated completion time of 5-7 minutes. RESULTS: One hundred four of 441 (24%) invitees participated, including 80/104 (77%) board-certified rheumatologists and 20/104 (19%) fellows. Survey participants identified UpToDate (85%), treatment guidelines (74%), and colleagues (54%) as relevant sources of knowledge for managing axSpA/AS. Of the participants, 64% and 53% considered themselves to be at least moderately familiar with the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network (ACR/SAA/SPARTAN) and Assessment of Spondyloarthritis international Society/European Alliance of Associations for Rheumatology (ASAS/EULAR) treatment recommendations for axSpA/AS, respectively. Whereas 69% of participants agreed or strongly agreed that disease activity scores are useful for making treatment decisions in axSpA/AS, only 37% measure patient-reported outcomes (PROs) frequently (≥ 50% of clinic visits) while 82% do so for C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). PROs are typically recorded during clinic encounters (65%) and CRP/ESR are obtained after the visit (86%). Of the participants, 57% and 47% considered the Bath Ankylosing Spondylitis Disease Activity Index and Ankylosing Spondylitis Disease Activity Score to be at least moderately useful for measuring disease activity in axSpA/AS, respectively; 41% and 37% thought the same about the ASAS 20% improvement criteria and Clinical Disease Activity Index, respectively. CONCLUSION: Treatment guidelines are an important resource for rheumatologists who manage patients with axSpA/AS. Although there is general agreement that disease activity monitoring is important, the implementation of the respective recommendations is lacking. Reasons may include lack of familiarity and an underdeveloped infrastructure to efficiently collect PROs.

Reporting of Facet Joint Inflammation in Lumbar Spine MRI Studies in Patients With Low Back Pain.

STUDY DESIGN: Retrospective. OBJECTIVE: We aimed to assess the frequency of facet joint inflammatory features noted in routine radiology reports of lumbar spine magnetic resonance imaging (MRI) studies among patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: Facet joint arthropathy is one of the most common causes of chronic low back pain. It may encompass various inflammatory imaging characteristics, such as facet joint effusion, bone marrow edema, and soft tissue edema. The extent to which radiology reports mention inflammatory features of the lumbar facet joints and the accuracy of these reports have not been investigated. MATERIALS AND METHODS: The authors performed a chart review on 49 subjects with previous facet-related interventions ( i.e . medial branch blocks or intra-articular facet joint injection) and MRI available in the medical record. One senior musculoskeletal radiologist and a musculoskeletal radiology fellow graded the inflammatory features using a published facet joint inflammation grading system [Gold Standard (GS)]. The authors identified the inflammatory markers mentioned in the radiology reports and calculated the sensitivity and positive predictive value of the radiology reports compared with GS readings. RESULTS: Compared with the GS, the sensitivity of radiology reports for facet joint effusion, bone marrow, and soft tissue edema ranged from 6% to 22%, and the positive predictive value ranged from 25% to 100%. L4/5 had the highest number of cases with inflammatory features noted on the reports. CONCLUSION: Inflammatory findings, such as facet joint effusion, bone marrow edema, and soft tissue edema, are not commonly identified in radiology reports. Further investigations are needed to determine the clinical importance of MRI-detected lumbar facet joint inflammatory features as a potential mechanism of nociception and as a predictor of outcomes following injections or other therapies.

Twenty Years of SPARTAN: From Inception to Impact (SPARTAN 2023 Annual Meeting Proceedings).

PURPOSE OF REVIEW: This review takes a look at the past, present, and future of SPARTAN, the Spondyloarthritis Research and Treatment Network, an organization of North American healthcare professionals dedicated to advancing research, education, and patient care in spondyloarthritis. RECENT FINDINGS: In 2022, SPARTAN completed the Classification of Axial SpondyloarthritiS Inception Cohort (CLASSIC) study, a collaboration with the Assessment in SpondyloArthritis International Society (ASAS). CLASSIC aimed to validate the 2009 ASAS classification criteria for axial spondyloarthritis. Other ongoing SPARTAN endeavors include the development of US referral recommendations for axial spondyloarthritis, an update of the 2019 ACR/SAA/SPARTAN treatment recommendations for axial spondyloarthritis and multiple educational initiatives. Twenty years after its inception, SPARTAN continues to grow and broaden its impact, guided by the SPARTAN vision of "a world free of spondyloarthritis through leadership in research and education."

Understanding Spondyloarthritis Pathogenesis: The Promise of Single-Cell Profiling.

PURPOSE OF REVIEW: Single-cell profiling, either in suspension or within the tissue context, is a rapidly evolving field. The purpose of this review is to outline recent advancements and emerging trends with a specific focus on studies in spondyloarthritis. RECENT FINDINGS: The introduction of sequencing-based approaches for the quantification of RNA, protein, or epigenetic modifications at single-cell resolution has provided a major boost to discovery-driven research. Fluorescent flow cytometry, mass cytometry, and image-based cytometry continue to evolve. Spatial transcriptomics and imaging mass cytometry have extended high-dimensional analysis to cells in tissues. Applications in spondyloarthritis include the indexing and functional characterization of cells, discovery of disease-associated cell states, and identification of signatures associated with therapeutic responses. Single-cell TCR-seq has provided evidence for clonal expansion of CD8+ T cells in spondyloarthritis. The use of single-cell profiling approaches in spondyloarthritis research is still in its early stages. Challenges include high cost and limited availability of diseased tissue samples. To harness the full potential of the rapidly expanding technical capabilities, large-scale collaborative efforts are imperative.

Factors Associated With Diagnostic Delay in Axial Spondyloarthritis: Impact of Clinical Factors and Social Vulnerability.

OBJECTIVE: Patients with axial spondyloarthritis (axSpA) often experience significant delay between symptom onset and diagnosis for reasons that are incompletely understood. We investigated associations between demographic, medical, and socioeconomic factors and axSpA diagnostic delay. METHODS: We identified patients meeting modified New York criteria for ankylosing spondylitis (AS) or 2009 Assessment of Spondyloarthritis International Society criteria for axSpA in the Mass General Brigham health care system between December 1990 and October 2021. We determined the duration of diagnostic delay, defined as the duration of back pain symptoms reported at diagnosis, as well as disease manifestations and specialty care prior to diagnosis from the electronic health record. We obtained each patient's Social Vulnerability Index (SVI) by mapping their address to the US Centers for Disease Control SVI Atlas. We examined associations among disease manifestations, SVI, and diagnostic delay using ordinal logistic regression. RESULTS: Among 554 patients with axSpA who had a median diagnostic delay of 3.8 years (interquartile range 1.1-10), peripheral arthritis (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.45-0.93) and older age at symptom onset (OR 0.83, 95% CI 0.78-0.88 per five years) were associated with shorter delay. AS at diagnosis (OR 1.85, 95% CI 1.30-2.63), a history of uveitis prior to diagnosis (OR 2.77, 95% CI 1.73-4.52), and higher social vulnerability (defined as national SVI 80th to 99th percentiles; OR 1.99, 95% CI 1.06-3.84) were associated with longer diagnostic delay. CONCLUSION: Older age at back pain onset and peripheral arthritis were associated with shorter delay, whereas uveitis was associated with longer diagnostic delay. Patients with higher socioeconomic vulnerability had longer diagnostic delay independent of clinical factors.

Comprehensive Grading System of Inflammatory Features of the Lumbar Facet Joints on Magnetic Resonance Imaging.

STUDY DESIGN: Retrospective. OBJECTIVE: We aimed to describe a magnetic resonance imaging (MRI)-based grading system of inflammatory features of the lumbar facet joints using an atlas and assess its reliability. SUMMARY OF BACKGROUND DATA: Chronic low back pain is often caused by facet joint arthropathy. Inflammatory features are often evident on MRI. While several grading systems of facet arthropathy have been described, there is scant data on the reliability of these systems, and none focus exclusively on inflammatory features. MATERIALS AND METHODS: We describe a grading system that assesses facet joint effusion, bone marrow edema, and soft tissue edema. Each feature was graded from 0 to 3 (facet edema) or 0 to 2 (bone marrow edema intensity and extent, soft tissue edema intensity and extent). Four spine experts graded MRIs of 50 subjects at the bilateral L3/4, L4/5, and L5/S1 levels. All subjects had symptomatic facet arthropathy and received therapeutic facet joint injections. We assessed the intra-reader and inter-reader reliability of each feature at each joint and summarized across all six joints. RESULTS: The mean age of subjects was 56 years (SD = 17), and 48% were female. The injections occurred at the L3/4 level in 12% of cases, at L4/5 in 88%, and at L5/S1 in 80% of cases. The intra-reader reliability kappa's for each feature ranged from 0.42 to 0.81. In contrast, the inter-reader reliability kappa values for each feature ranged from 0.37 to 0.54. CONCLUSION: MRI inflammatory features of the lumbar facet joints are often noted in patients with low back pain. The proposed grading system is reliable and could serve as a research tool for studies assessing the clinical relevance and prognostic value of these features.

Functional genomics implicates natural killer cells as potential key drivers in the pathogenesis of ankylosing spondylitis.

Objective: Multiple lines of evidence indicate that ankylosing spondylitis (AS) is a lymphocyte-driven disease. However, which lymphocyte populations are critical in AS pathogenesis is not known. In this study, we aimed to identify the key cell types mediating the genetic risk in AS using an unbiased integrative functional genomics approach. Methods: We integrated GWAS data with epigenomic and transcriptomic datasets of immune cells in healthy humans. To quantify enrichment of cell type-specific open chromatin regions or gene expression in AS risk loci, we used three published methods which have identified cell types for other diseases. Additionally, we performed co-localization analyses between GWAS risk loci and genetic variants associated with gene expression (eQTL) to find putative target genes of AS risk variants. Results: Natural killer (NK) cell-specific open chromatin regions are significantly enriched in heritability for AS, compared to other immune cell types such as T cells, B cells, and monocytes. This finding was consistent between two AS GWAS. Using RNA-seq data, we validated that genes in AS risk loci are enriched in NK cell-specific gene expression. Expression levels of AS-associated genes, such as RUNX3, TBX21, TNFRSF1A, and NPEPPS, were found to be highest in NK cells compared to five T cell subsets. Using the human Space-Time Gut Cell Atlas we found significant upregulation of AS-associated genes predominantly in NK cells. Co-localization analysis revealed four AS risk loci affecting regulation of candidate target genes in NK cells: two known loci, ERAP1 and TNFRSF1A, and two under-studied loci, ENTR1 (aka SDCCAG3) and B3GNT2. Conclusion: Our results point to NK cells as potential key drivers in the development of AS and highlight four putative target genes for functional follow-up in NK cells.

Predictors of Outcomes After Lumbar Intra-Articular Facet Joint Injections and Medial Branch Blocks: A Scoping Review.

STUDY DESIGN: A scoping review. OBJECTIVE: We aimed to identify and describe the factors associated with the patient-reported response after lumbar intra-articular facet joint (FJ) injections or medial branch blocks (MBBs). SUMMARY OF BACKGROUND DATA: FJ osteoarthritis is among the most common causes of chronic low back pain. Management often includes FJ intra-articular injection and MBBs (which may be followed by radiofrequency ablation of the nerves innervating these joints). However, the success of these approaches is variable, prompting interest in identifying patient characteristics (imaging features, clinical signs, and among others) associated with response to these types of facet injections. MATERIALS AND METHODS: We performed a literature search on factors associated with patient-reported outcomes after lumbar FJ intra-articular injections or MBBs for patients with low back pain published in English or Spanish between 2000 and 2023. We excluded duplicate papers that did not describe factors associated with outcomes or those describing other interventions. We collected data on the association of these factors with patient-reported outcomes. RESULTS: Thirty-seven studies met the inclusion criteria and were analyzed. These studies evaluated factors, such as age, depression, and single photon emission computed tomography (SPECT), and among variables. Age and imaging findings of facet arthropathy were the most frequently described factors. Imaging findings of FJ arthropathy and positive SPECT were often associated with positive results after intra-articular FJ injections or MBBs. In contrast, younger age and smoking were frequently associated with less favorable clinical outcomes. CONCLUSION: Numerous factors were considered in the 37 studies included in this review. Imaging findings of facet arthropathy, duration of pain, and positive SPECT were consistently associated with favorable results after facet interventions.

Activity of axial spondyloarthritis after one year of anti-tumor necrosis factor therapy among patients with inflammatory bowel diseases.

The disease activity of axSpA after initiating anti-TNF agents for inflammatory bowel diseases (IBD) is poorly understood. We sought to examine the disease activity of axial spondyloarthritis (axSpA) after initiation of anti-tumor necrosis factor (TNF) agents among patients with IBD. This retrospective cohort study included adults with IBD and axSpA who initiated anti-TNF agents between 1/1/2012-10/1/2021 at a large academic center. The primary outcome was symptom resolution (SR) of axSpA at 12 months ("0/10 pain" or "no pain" or "controlled pain" with no morning stiffness and no use of daily NSAIDs). The secondary outcome was clinical remission (CR) of IBD at 12 months (simple clinical colitis activity index <3, Harvey-Bradshaw Index <5, or provider assessment with no use of oral/IV steroids for 30 days). Associations between baseline characteristics and SR of axSpA were examined using logistic regression. 82 patients with axSpA and IBD initiated anti-TNF agents. At 12 months, 52% and 74% achieved SR of axSpA and CR of IBD, respectively. IBD duration <5 years (OR 3.0, 95% CI 1.2-7.5) and adalimumab use (reference: all other anti-TNFs; OR 2.7, 95% CI 1.002-7.1) were associated with SR of axSpA at 12 months. 52% of patients with axSpA and IBD achieved SR of axSpA at 12 months after initiating anti-TNF therapy. Shorter disease duration and adalimumab use may be associated with higher odds of SR. Larger studies are needed to confirm these findings, examine additional clinical predictors of SR, and identify more effective therapeutics for this population.

Grading Systems of Lumbar Facet Joint Inflammatory Changes on Magnetic Resonance Imaging: A Scoping Review.

STUDY DESIGN: A scoping review. OBJECTIVE: We aimed to identify and characterize grading systems of the inflammatory features of the lumbar facet joints (FJs) noted on magnetic resonance imaging and summarize their reliability. SUMMARY OF BACKGROUND DATA: Chronic low back pain is one of the most common causes of disability worldwide and is frequently accompanied by FJ osteoarthritis. Inflammatory changes in the lumbar FJs are commonly noted in imaging studies of patients with FJ osteoarthritis and low back pain. Several grading systems for these inflammatory changes have been developed. However, these grading system's features and reliability have yet to be reviewed. MATERIALS AND METHODS: We performed a literature search of studies reporting grading systems for FJ inflammatory changes published in English or Spanish between 1985 and 2022. We collected data on reported interreader reliability measures of each grading system. Finally, we compared the features of inflammation described by each system. RESULTS: Six studies met the inclusion criteria and were used in our analysis. Features commonly graded in these systems are the hyperintensity signal noted within the FJ, bone marrow edema, and the extent of the soft-tissue edema surrounding the FJs. We found that the interreader reliability measures ranged from 0.56 to 0.96. CONCLUSIONS: Only 6 studies have reported methods for documenting inflammation in the FJs. Studies varied in the precise tissues and phenomena included in the grading systems. However, the systems were generally reliable. Future studies should document the reliability of these methods when independent investigators are not involved in developing the classification schemes. Further work might combine one or more of these measures to establish a standard and reliable grading system for inflammatory changes in the FJs, including signal intensity within the joint, bone marrow edema, and soft-tissue inflammation.

A glance into the future of diagnosis and treatment of spondyloarthritis.

The last two decades have seen major developments in the field of spondyloarthritis (SpA), but there are still important unmet needs to address. In the future, we envisage important advances in the diagnosis and treatment of SpA. In the diagnosis of SpA, the use of online and social media tools will increase awareness of the disease and facilitate the referral of patients to rheumatology clinics. In addition, more specific diagnostic tests will be available, especially advanced imaging methods and new biomarkers. This will allow most patients to be diagnosed at an early stage of the disease. In the treatment of SpA, an increasing number of novel treatment targets can be expected, most of which will be directed against intracellular enzymes. We hope to see more strategy trials shaping treatment pathways in SpA and accommodating principals of precision medicine. Approved treatment options will be available for both axial and peripheral SpA. We also hope to intervene not only at the inflammation level but also at the level of underlying immunological processes that might be associated with a higher probability of long-standing remission if not a cure. Finally, artificial intelligence techniques will allow for the analysis of large-scale data to answer relevant research questions for the diagnosis and management of patients with SpA.

Spondyloarthritis in inflammatory bowel disease cohorts: systematic literature review and critical appraisal of study designs.

To critically appraise study designs evaluating spondyloarthritis (SpA) phenotypes in patients with inflammatory bowel disease (IBD). A systematic literature review of PubMed, Ovid, Scopus, Cinahl, Medline, Web of Science, and Cochrane databases was performed. Articles published from January 2000 - March 2020 were included if they evaluated the prevalence/incidence of musculoskeletal disease in cohorts of IBD patients. Most of the 69 included studies were clinic based (54/69, 78%), single center (47/69, 68%) and cross-sectional (60/69, 87%). The median prevalence of axial and peripheral SpA in IBD was 5% (range 1 - 46%) and 16% (range 1 - 43%), respectively. In 38 studies that evaluated axial disease in prospectively enrolled patients, inflammatory back pain was analyzed in 53%. SpA classification criteria were used in 68% and imaging was performed in 76%. In 35 studies that evaluated peripheral disease in prospectively enrolled patients, SpA classification criteria were used in 46%. A physical exam was performed in 74%, and it was performed by a rheumatologist in 54% of studies with a physical exam. Sub-phenotypes of peripheral SpA (mono- or oligo-arthritis, polyarthritis, enthesitis, dactylitis) were variably reported. Seventy-four percent of studies did not mention whether osteoarthritis and fibromyalgia had been assessed or excluded. The spectrum of SpA phenotypes in IBD patients remains incompletely characterized. Future studies should focus on standardizing the variables collected in IBD-SpA cohorts and defining musculoskeletal phenotypes in IBD-SpA in order to better characterize this disease entity and advance the field for clinical and research purposes.

The potent and selective RIPK2 inhibitor BI 706039 improves intestinal inflammation in the TRUC mouse model of inflammatory bowel disease.

Mouse and human data implicate the NOD1 and NOD2 sensors of the intestinal microbiome and the associated signal transduction via the receptor interacting protein kinase 2 (RIPK2) as a potential key signaling node for the development of inflammatory bowel disease (IBD) and an attractive target for pharmacological intervention. The TRUC mouse model of IBD was strongly indicated for evaluating RIPK2 antagonism for its effect on intestinal inflammation based on previous knockout studies with NOD1, NOD2, and RIPK2. We identified and profiled the BI 706039 molecule as a potent and specific functional inhibitor of both human and mouse RIPK2 and with favorable pharmacokinetic properties. We dosed BI 706039 in the spontaneous TRUC mouse model from age 28 to 56 days. Oral, daily administration of BI 706039 caused dose-responsive and significant improvement in colonic histopathological inflammation, colon weight, and terminal levels of protein-normalized fecal lipocalin (all P values <0.001). These observations correlated with dose responsively increasing systemic levels of the BI 706039 compound, splenic molecular target engagement of RIPK2, and modulation of inflammatory genes in the colon. This demonstrates that a relatively low oral dose of a potent and selective RIPK2 inhibitor can modulate signaling in the intestinal immune system and significantly improve disease associated intestinal inflammation.NEW & NOTEWORTHY The RIPK2 kinase at the apex of microbiome immunosensing is an attractive target for pharmacological intervention. A low oral dose of a RIPK2 inhibitor leads to significantly improved intestinal inflammation in the murine TRUC model of colitis. A selective and potent inhibitor of the RIPK2 kinase may represent a new class of therapeutics that target microbiome-driven signaling for the treatment of IBD.

The impact of genetic background and sex on the phenotype of IL-23 induced murine spondyloarthritis.

BACKGROUND: Overexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles has been reported to result in spondyloarthritis-like disease. The impact of genetic background and sex on the disease phenotype in this model has not been investigated. METHODS: We compared male B10.RIII mice with male C57BL/6 mice, and male with female B10.RIII mice after hydrodynamic injection of IL-23 enhanced episomal vector (EEV) at 8-12 weeks of age. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks and tissues were harvested for histology, flow cytometry and gene expression analysis. Serum cytokine levels were determined by ELISA. FINDINGS: Male B10.RIII mice developed arthritis in the forepaws and feet within 6 days after IL-23 EEV injection; they also exhibited psoriasis-like skin disease, colitis, weight loss, and osteopenia. In contrast to previous reports, we did not observe spondylitis or uveitis. Male C57BL/6 mice injected with IL-23 EEV had serum IL-23 levels comparable with B10.RIII mice and developed skin inflammation, colitis, weight loss, and osteopenia but failed to develop arthritis. Female B10.RIII mice had more severe arthritis than male B10.RIII mice but did not lose weight. CONCLUSIONS: The phenotype of IL-23 induced disease in mice is controlled by genetic background and sex of the animals. The development of extra-articular manifestations but absence of arthritis in C57BL/6 mice suggests that organ-specificity of IL-23 driven inflammation is genetically determined. The mechanisms behind the strain-specific differences and the sexual dimorphism observed in this study may be relevant for human spondyloarthritis and warrant further exploration.

Recognizing Axial Spondyloarthritis: A Guide for Primary Care.

Axial spondyloarthritis (axSpA) is an important cause of chronic low back pain and affects approximately 1% of the US population. The back pain associated with axSpA has a characteristic pattern referred to as inflammatory back pain (IBP). Features of IBP include insidious onset before age 45 years, association with morning stiffness, improvement with exercise but not rest, alternating buttock pain, and good response to treatment with nonsteroidal anti-inflammatory drugs. In patients with IBP, it is essential to look for other features associated with spondyloarthritis (SpA), such as enthesitis, dactylitis, peripheral arthritis, extra-articular manifestations (eg, psoriasis, uveitis, or inflammatory bowel disease), human leukocyte antigen B27 positivity, and a family history of SpA. Axial SpA is underrecognized, and a delay of several years between symptom onset and diagnosis is common. However, with new and effective therapies available for the treatment of active axSpA, early recognition and diagnosis are of critical importance. For this narrative review, we conducted a literature search of English-language articles using PubMed. Individual searches were performed to identify potential articles of interest related to axSpA (search terms: ["axSpA" OR "axial SpA" OR "axial spondyloarthritis" OR "ankylosing spondylitis"]) in combination with terms related to IBP ("inflammatory back pain" OR "IBP" OR "chronic back pain" OR "CBP" OR "lower back pain" OR "LBP"), diagnosis (["diagn∗" OR "classification"] AND ["criteria" OR "recommend∗" OR "guidelines"]), and referral ("refer∗"). No date range was formally selected, as we were interested in providing an overview of the evolution of these concepts in clinical practice. We supplemented the review with insights based on our clinical expertise. Patients with chronic back pain should be screened for IBP and other SpA features; suspicion for axSpA should trigger referral to a rheumatologist for further evaluation.