IL-6 as a keystone cytokine in health and disease.

Interleukin 6 (IL-6) has a broad effect on cells of the immune system and those not of the immune system and often displays hormone-like characteristics that affect homeostatic processes. IL-6 has context-dependent pro- and anti-inflammatory properties and is now regarded as a prominent target for clinical intervention. However, the signaling cassette that controls the activity of IL-6 is complicated, and distinct intervention strategies can inhibit this pathway. Clinical experience with antagonists of IL-6 has raised new questions about how and when to block this cytokine to improve disease outcome and patient wellbeing. Here we discuss the effect of IL-6 on innate and adaptive immunity and the possible advantages of various antagonists of IL-6 and consider how the immunobiology of IL-6 may inform clinical decisions.

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.

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."

Exercise Therapy Research in Ankylosing Spondylitis-Induced Back Pain: A Bibliometric Study (2004-2023).

BACKGROUND Ankylosing spondylitis (AS), a chronic inflammatory disease predominantly causing back pain, affects up to 0.5% of the global population, more commonly in males. Frequently undiagnosed in early stages, AS is often associated with comorbid depression and anxiety, imposing significant healthcare burdens. Despite available pharmaceutical treatments, exercise therapy (ET) has emerged as an effective, side-effect-free alternative, particularly for managing AS-induced back pain. This study aims to explore the research trends in ET for treating AS back pain from 2004-2023. MATERIAL AND METHODS A comprehensive analysis of 437 articles, sourced from the Science Citation Index-Expanded within the Web of Science Core Collection, was conducted using CiteSpace 6.2.R5. This study spanned from 2004 to October 15, 2023, examining publications, authors, institutions, and keywords to assess keyword co-occurrences, temporal progressions, and citation bursts. RESULTS Research interest in ET for AS began escalating around 2008 and has since shown steady growth. The USA emerged as a significant contributor, with Van der Heijde, Desiree, and RUDWALEIT M being notable authors. Key institutions include Assistance Publique Hopitaux Paris and UDICE-French Research Universities, with ANN RHEUM DIS being the most influential journal. The field's evolution is marked by interdisciplinary integration and branching into various sub-disciplines. CONCLUSIONS Exercise therapy for AS-induced back pain is a growing research area, necessitating further exploration in clinical management and rehabilitation strategies. The relationship between ET and osteoimmunological mechanisms remains a focal point for future research, with a trend towards personalized and interdisciplinary treatment approaches.

Programmed cell death 10 can be used as a potential biomarker for ankylosing spondylitis diagnosis and treatment.

STUDY DESIGN: Diagnostic study. OBJECTIVE: Programmed cell death 10 (PDCD10) is a new versatile molecule involved in signal transduction regulation in angiogenesis and tumors. The potential of using it as a biomarker for the diagnosis of ankylosing spondylitis (AS) is still unknown. SETTING: University laboratory in Gannan Medical University, China. METHODS: Expression of PDCD10 was analyzed using clinical samples of patients with AS and Gene Expression Omnibus (GEO) data GDS5231. To explore its function, PDCD10 was upregulated and downregulated in synovial cells. Spearman analysis was used to study the association between PDCD10 and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The Receiver operating characteristic (ROC) curve was applied to evaluate the sensitivity and specificity of PDCD10. RESULTS: Expression of PDCD10 was upregulated in patients with AS and it is capable of promoting the calcification of synovial cells. A positive association between PDCD10 and the BASDAI and the mSASSS was observed. The area under the ROC curve (AUC) of PDCD10 was 82% with a 95% confidence interval of [0.772, 0.868]. CONCLUSIONS: PDCD10 is upregulated in patients with AS and it can promote the calcification of synovial cells in vitro. PDCD10 is positively associated with outcome parameters of AS. ROC analysis of PDCD10 suggests that it can be used as a biomarker for the diagnosis and treatment of AS.

Can a Nomogram Predict Survival After Treatment for an Ankylosing Spondylitis Cervical Fracture in a Patient With Neurologic Impairment? A National, Multicenter Study.

BACKGROUND: Ankylosing spondylitis-related cervical spine fracture with neurologic impairment (ASCF-NI) is a rare but often lethal injury. Factors independently associated with survival after treatment remain poorly defined, and identifying patients who are likely to survive the injury remains challenging. QUESTIONS/PURPOSES: (1) What factors are independently associated with survival after treatment among patients with ASCF-NI? (2) Can a nomogram be developed that is sufficiently simple for clinicians to use that can identify patients who are the most likely to survive after injury? METHODS: This retrospective study was conducted based on a multi-institutional group of patients admitted and treated at one of 29 tertiary hospitals in China between March 1, 2003, and July 31, 2019. A total of 363 patients with a mean age of 53 ± 12 years were eventually included, 343 of whom were male. According to the National Household Registration Management System, 17% (61 of 363) died within 5 years of injury. Patients were treated using nonsurgical treatment or surgery, including procedures using the anterior approach, posterior approach, or combined anterior and posterior approaches. Indications for surgery included three-column injury, unstable fracture displacement, neurologic impairment or continuous progress, and intervertebral disc incarceration. By contrast, patients generally received nonsurgical treatment when they had a relatively stable fracture or medical conditions that did not tolerate surgery. Demographic, clinical, and treatment data were collected. The primary study goal was to identify which factors are independently associated with death within 5 years of injury, and the secondary goal was the development of a clinically applicable nomogram. We developed a multivariable Cox hazards regression model, and independent risk factors were defined by backward stepwise selection with the Akaike information criterion. We used these factors to create a nomogram using a multivariate Cox proportional hazards regression analysis. RESULTS: After controlling for potentially confounding variables, we found the following factors were independently associated with a lower likelihood of survival after injury: lower fracture site, more-severe peri-injury complications, poorer American Spinal Injury Association (ASIA) Impairment Scale, and treatment methods. We found that a C5 to C7 or T1 fracture (ref: C1 to C4 and 5; hazard ratio 1.7 [95% confidence interval 0.9 to 3.5]; p = 0.12), moderate peri-injury complications (ref: absence of or mild complications; HR 6.0 [95% CI 2.3 to 16.0]; p < 0.001), severe peri-injury complications (ref: absence of or mild complications; HR 30.0 [95% CI 11.5 to 78.3]; p < 0.001), ASIA Grade A (ref: ASIA Grade D; HR 2.8 [95% CI 1.1 to 7.0]; p = 0.03), anterior approach (ref: nonsurgical treatment; HR 0.5 [95% CI 0.2 to 1.0]; p = 0.04), posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.8]; p = 0.006), and combined anterior and posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.9]; p = 0.02) were associated with survival. Based on these factors, a nomogram was developed to predict the survival of patients with ASCF-NI after treatment. Tests revealed that the developed nomogram had good performance (C statistic of 0.91). CONCLUSION: The nomogram developed in this study will allow us to classify patients with different mortality risk levels into groups. This, coupled with the factors we identified, was independently associated with survival, and can be used to guide more appropriate treatment and care strategies for patients with ASCF-NI. LEVEL OF EVIDENCE: Level III, therapeutic study.

Defining and managing flares in axial spondyloarthritis.

PURPOSE OF REVIEW: Flares correspond to fluctuations in disease activity or symptoms. They should be avoided in chronic inflammatory diseases. In axial spondyloarthritis (axSpA), work is ongoing to better conceptualise and treat flares. This review highlights recent data on the definition and management of flares in axSpA. RECENT FINDINGS: Many definitions of flares have been used in clinical trials, limiting the interpretation and comparison of studies. The expert group Assessment of SpondyloArthritis International Society (ASAS) developed a data-driven definition of flares/disease worsening: an increase in Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) of at least 0.9 points, for use in axSpA clinical trials. Flares are more challenging to define in clinical practice because of their multifaceted nature. Qualitative studies have shown that flares from the patient's perspective are related not only to disease activity, but also to fatigue, mood, sleep and general well-being. The management of axSpA relies on a treat-to-target (T2T) strategy and aims at reaching clinical remission while monitoring closely disease activity to prevent and shorten flares. SUMMARY: The concept of flares has been clarified, and definitions have been developed for use in trials. The T2T approach aims at minimising flares in axSpA. The early recognition of flares and their severity may lead to better management.

The genetic backbone of ankylosing spondylitis: how knowledge of genetic susceptibility informs our understanding and management of disease.

Ankylosing spondylitis (AS) is a seronegative, chronic inflammatory arthritis with high genetic burden. A strong association with HLA-B27 has long been established, but to date its contribution to disease aetiology remains unresolved. Recent insights through genome wide studies reveal an increasing array of immunogenetic risk variants extraneous to the HLA complex in AS cohorts. These genetic traits build a complex profile of disease causality, highlighting several molecular pathways associated with the condition. This and other evidence strongly implicates T-cell-driven pathology, revolving around the T helper 17 cell subset as an important contributor to disease. This prominence of the T helper 17 cell subset has presented the opportunity for therapeutic intervention through inhibition of interleukins 17 and 23 which drive T helper 17 activity. While targeting of interleukin 17 has proven effective, this success has not been replicated with interleukin 23 inhibition in AS patients. Evidence points to significant genetic diversity between AS patients which may, in part, explain the observed refractoriness among a proportion of patients. In this review we discuss the impact of genetics on our understanding of AS and its relationship with closely linked pathologies. We further explore how genetics can be used in the development of therapeutics and as a tool to assist in the diagnosis and management of patients. This evidence indicates that genetic profiling should play a role in the clinician's choice of therapy as part of a precision medicine strategy towards disease management.

Sustained improvements in EQ-5D utility scores and self-rated health status in patients with ankylosing spondylitis after spa treatment including low-dose radon - an analysis of prospective radon indication registry data.

BACKGROUND: Patients with ankylosing spondylitis (AS) have significantly lower quality of life (QoL) than the general population. Holistic interventions addressing QoL comprise spa- or balneotherapy including radon. These interventions have shown to be beneficial in reducing pain and improving QoL in AS-patients. We explored the association of spa-therapy including low-dose radon with QoL in AS-patients over an extended time period. METHODS: Registry data collected for the "Radon indication registry" in the Austrian Gastein valley comprising data on QoL (EuroQol EQ-5D) directly before the treatment (baseline), directly(t1), 3 (t2); 6(t3) and 9(t4) months after the treatment, age, sex and body mass index (BMI) were analysed. Linear regression models explored the association of measurement time with 1) EQ-5D-5L utilities and 2) EuroQol visual analogue scale (VAS) score. Alterations of 0.05 (utilities) and 5.00 (VAS) were considered clinically relevant. RESULTS: Two-hundred-ninety-one AS-patients were included in the analyses. Forty-four percent (n = 128) were women, the mean age was 52 (SD 10) and the average BMI was 26 (SD 4). Utilities (t1: 0.09 [0.07;0.11]; t2: 0.08 [0.06; 0.10]; t3: 0.06 [0.05;0.09]; t4: 0.04 [0.02;0.06]) and VAS (t1: 11.68 [9.38; 13.97]; t2: 12.20 [9.78; 14.61]; t3: 9.70 [7.24; 12.17]; t4: 6.11 [3.57; 8.65]) were significantly higher at all timepoints compared to baseline. Improvements were clinically relevant at all timepoints in case of the VAS and until 6 months after treatment for the utilities. CONCLUSION: AS-patients who received spa therapy including radon show significantly and clinically relevant improvements in Qol until 6-9 months after treatment.

Adherence, Efficacy, and Safety of Wearable Technology-Assisted Combined Home-Based Exercise in Chinese Patients With Ankylosing Spondylitis: Randomized Pilot Controlled Clinical Trial.

BACKGROUND: Clinical practice guidelines recommend that exercise is essential in the self-management of ankylosing spondylitis (AS). Attending supervised interventions requiring periodic medical center visits can be difficult and patients may decline participation, whereas effective home-based exercise interventions that do not require regular medical center visits are likely to be more accessible for AS patients. OBJECTIVE: The goal of the research was to investigate the adherence, efficacy, and safety of a wearable technology-assisted combined home-based exercise program in AS. METHODS: This was a 16-week investigator-initiated, assessor-blinded, randomized, pilot controlled trial conducted at Chinese People's Liberation Army General Hospital. We enrolled patients with AS who had no regular exercise habits and had been stable in drug treatment for the preceding month. Patients were randomly assigned (1:1) using a computer algorithm. An exercise program consisting of moderate-intensity aerobic exercise and functional exercise was given to the patients in the intervention group. The exercise intensity was controlled by a Mio FUSE Heart Rate Monitor wristband, which uses photoplethysmography to measure heart rate. Patients in the control group received usual care. The primary outcome was the difference in the Ankylosing Spondylitis Disease Activity Score (ASDAS). The secondary outcomes were patient global assessment (PGA), physician global assessment (PhGA), total pain, nocturnal pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BAS Functional Index (BASFI), BAS Metrology Index (BASMI), Spondyloarthritis International Society Health Index (ASAS HI), 36-item Short Form Survey (SF-36), maximal oxygen uptake (VO2) max, body composition, range of motion of joints, and muscle endurance tests. Retention rate, adherence rate, barriers to being active, and adverse events were also assessed. RESULTS: A total of 77 patients were screened, of whom 55 (71%) patients were enrolled; 2% (1/55) withdrew without treatment after randomization. Patients were assigned to the intervention (n=26) or control group (n=28). The median adherence rate of the prescribed exercise protocol was 84.2% (IQR 48.7%-97.9%). For the primary outcome, between-group difference of ASDAS was significant, favoring the intervention (-0.2, 95% CI -0.4 to 0.02, P=.03). For the secondary outcomes, significant between-group differences at 16 weeks were detected in PGA, PhGA, total pain, BASDAI, BASDAI-fatigue, BASDAI-spinal pain, BASDAI-morning stiffness intensity, BASFI, and BASMI. Moreover, the frequency of difficulty in ASAS HI-motivation at 16 weeks was less in the intervention group (P=.03). Between-group difference for change from baseline were also detected in VO2 max, SF-36, back extensor endurance test, and the range of motion of cervical lateral flexion at 16 weeks. Lack of time, energy, and willpower were the most distinct barriers to being active. Incidences of adverse events were similar between groups (P=.11). CONCLUSIONS: Our pilot study suggests that this technology-assisted combined home-based exercise program can improve the clinical outcomes of patients with AS who have no exercise habit, with good adherence and safety profile. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024244; http://www.chictr.org.cn/showproj.aspx?proj=40176.

The Impact of a Theory-Based mHealth Intervention on Disease Knowledge, Self-efficacy, and Exercise Adherence Among Ankylosing Spondylitis Patients: Randomized Controlled Trial.

BACKGROUND: Patient education is recommended as an integral part of disease management in ankylosing spondylitis (AS), a chronic rheumatic disease that predominantly affects young males and requires long-term disease management. Convenient and cost-effective approaches to deliver patient education are required to these patients. OBJECTIVE: This study aimed to examine the effects of a theory-based educational intervention delivered through a social networking app, WeChat, on disease knowledge, self-efficacy, exercise adherence, and health outcomes in Chinese AS patients. METHODS: This study was a single-blind randomized controlled trial conducted in a tertiary hospital in Chengdu, China. Eligible participants were randomly allocated to the intervention or control group. Participants in the control group received standard care. The intervention group received the health belief model (HBM)-based educational intervention, consisting of 4 individual educational sessions and educational information sharing through WeChat, the predominant social networking app in China. The primary outcomes were disease knowledge, self-efficacy, and exercise adherence. The secondary outcomes were disease activity and physical function. Data were collected at baseline and at the end of the intervention (12th week). Chi-square test, t test, Mann-Whitney U tests were used to examine the effects of educational intervention. RESULTS: This study included 118 patients with AS. The majority of participants were male (93/118, 78.8%). Around half of them were married (56/118, 47.5%), never smoked (70/118, 59.3%), and had college educational level or above (62/118, 52.5%). At posttest, participants in the intervention group had higher disease knowledge (all P<.001) and self-efficacy (P<.001), and a larger proportion of participants in the intervention group adhered to regular exercise routines than those in the control group (P=.003). The within-group analyses for the intervention group showed increases in all scores of disease knowledge (all P<.001) and self-efficacy score (P<.001), but only correct answer score (P=.04) and general knowledge score (P=.002) of disease knowledge in the control group improved. The within-group analysis for the control group found a decline of physical function (P=.002) but no significant change in disease activity (P>.05). The within-group analysis for the intervention group showed no significant change in disease activity or physical function (P>.05). At posttest, no statistically significant difference was found on disease activity or physical function between the intervention and control groups (P>.05). CONCLUSIONS: The HBM-based educational intervention through WeChat can effectively improve patient disease knowledge, self-efficacy, and exercise adherence. WeChat is feasible and effective to deliver patient education for patients with chronic diseases such as AS. This mHealth intervention can be integrated into routine rheumatology care. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-16009293; https://tinyurl.com/swxt8xk7.

[Axial spondyloarthritis : Update on management based on the interdisciplinary S3 guidelines on axial spondyloarthritis including early forms and ankylosing spondylitis]. / Axiale Spondyloarthritis : Update zum Management basierend auf der interdisziplinären S3-Leitlinie "Axiale Spondyloarthritis inklusive Frühformen und Morbus Bechterew".

This review article presents the innovations in the update of the S3 guidelines on axial spondylarthritis. The total of eight new recommendations address the areas of the consideration of differential diagnoses, coordination of comorbidity management, including a vaccination strategy, treatment targets, safety of nonsteroidal anti-inflammatory drugs (NSAID), treatment response to biological disease-modifying antirheumatic drugs (bDMARD) and discontinuation strategies when remission has been achieved. In this article the authors deal particularly with the areas of early diagnosis and referral as well as exercise therapy and drug treatment.

Axial Spondyloarthritis in the Chiropractic Care Setting: A Systematic Literature Review.

ABSTRACT: Diagnosis of axial spondyloarthritis (axSpA), an immune-mediated inflammatory disease, is commonly associated with chronic inflammatory back pain (IBP) and often occurs years after initial onset of clinical symptoms. Recognition of IBP is important for timely referral of patients with suspected axSpA to a rheumatologist. Patients with all types of back pain are treated in chiropractic care, but the proportion of patients with undiagnosed axSpA is unknown. This systematic literature review investigated the presence of axSpA in patients treated by chiropractors and identified the chiropractor's role in axSpA diagnosis, referral, and management. A PubMed search was conducted using the following search strings: "chiropract*" AND ("sacroiliac" OR "back pain" OR "spondyloarthritis" OR "ankylosing spondylitis"); English language, since 2009; and (chiropractic OR chiropractor) AND (ankylosing spondylitis OR axial spondyloarthritis), with no date limits. Of 652 articles identified in the searches, 27 met the inclusion criteria. Although back pain was identified as a common reason for patients seeking chiropractic care, there was no mention of axSpA, ankylosing spondylitis, or the distinction between mechanical and IBP. Data from relevant articles suggested that the majority of patients seeking chiropractic care have lower back pain, whereas no articles reported axSpA in this patient population. The near absence of any identified articles on axSpA in chiropractic care may be due to underrecognition of axSpA, resulting in delayed rheumatology referral and appropriate management. Better awareness and increased use of validated screening tools could reduce diagnostic delay of axSpA in chiropractic care.

[Recommendations for diagnosis and treatment of ankylosing spondylitis].

Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the sacroiliac joints, spine and peripheral joints. In China, standardized diagnosis and treatment of AS is still to be popularized. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed standardization of diagnosis and treatment of AS. The purposes are: (1) to standardize the diagnosis and evaluation of AS; (2) to promote rational use of non-steroidal anti-inflammatory drugs, biological as well as traditional disease modifying anti-rheumatic drugs, so as to improve the patient's quality of life.

Exercise in the treatment of ankylosing spondylitis.

Seronegative spondyloarthritis is a progressive inflammatory disease with a wide and varied range of symptoms. Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by pain and structural changes. Ankylosing spondylitis is characterized by functional disorders such as reduced mobility and axial deformity, leading to a decrease in patient quality of life. The purpose of this article is to provide basic information on therapeutic options for exercise in the treatment of ankylosing spondylitis. Therapeutic exercise is the most important non-pharmacological intervention in patients. In addition to positive metabolic effects, exercise also plays an important role in improving spinal mobility and muscle strength. Maintaining proper postural posture appears to play a key role in patients with ankylosing spondylitis. Muscle contraction stimulates and promotes the secretion of cytokines called myokines. The best known is interleukin-6 (IL-6). This myokine also acts indirectly in the expression of tumor necrosis factor alpha (TNF-α). Exercise improves quality of life, physical condition, and symptoms associated with ankylosing spondylitis.

Osteoimmunological insights into the pathogenesis of ankylosing spondylitis.

Ankylosing spondylitis (AS) is inflammatory arthritis predominantly affecting the spine, which is involved in the disorders of both immune and skeletal systems. The exact pathogenesis of AS is not fully understood. Osteoimmunology is a new subject of study in inflammatory arthritis, in particular the pathogenic events involved in the cross-regulation of both skeletal and immune systems. In this review, we discuss osteoimmunological and pathological changes of AS in the spine that are characterized by altered osteogenesis and osteolytic bone destruction, accompanied by the changes of the immune system. It was revealed that bone cells like mesenchymal stem cells, osteoblast, and osteoclast in crossing talking with immune cells such as T cells, B cells coregulate to the pathogenesis of AS. Further, an array of cytokines and molecules expressed by both skeletal and immune systems contribute to these complex interplays. Understanding the cellular and molecular mechanisms underlying the pathogenesis of AS will lay a foundation for the exploration of the potential new treatment to AS.

Educational needs and challenges in axial spondyloarthritis.

PURPOSE OF REVIEW: Axial spondyloarthritis (axSpA) affects 0.5-1% of the population in many regions of the world. This review summarizes the challenges in medical education around axSpA with attention to evidence around delayed diagnosis, clinician familiarity with typical axSpA features, such as inflammatory back pain and adherence to accepted management principles. RECENT FINDINGS: Clinicians who commonly manage patients with chronic back pain or other typical axSpA features are not consistently aware of the concept of inflammatory back pain and common extra-spinal manifestations. Further, clinicians may not be familiar with the nonradiographic spectrum of axSpA. Management of patients with possible axSpA does not consistently follow principles that would establish an axSpA diagnosis, and diagnosis of axSpA remains delayed by 6-7 years on average, with evidence suggesting management disparities on the basis of sex and race in some cases. Referral recommendations have increased the probability of axSpA diagnosis up to about 40% and, may complement educational efforts in axSpA. SUMMARY: Educational efforts in axSpA should focus on providing front-line clinicians with a better understanding of inflammatory back pain, the nonradiographic form of axSpA, and accepted principles in axSpA management.

Evaluation of the impact of a nurse-led program of patient self-assessment and self-management in axial spondyloarthritis: results of a prospective, multicentre, randomized, controlled trial (COMEDSPA).

OBJECTIVE: To evaluate the impact of a nurse-led program of self-management and self-assessment of disease activity in axial spondyloarthritis. METHODS: Prospective, randomized, controlled, open, 12-month trial (NCT02374749). Participants were consecutive axial spondyloarthritis patients (according to the rheumatologist) and nurses having participated in a 1-day training meeting. The program included self-management: educational video and specific video of graduated, home-based exercises for patients; and self-assessment: video presenting the rationale of tight monitoring of disease activity with composite scores (Ankylosing Spondylitis Disease activity Score, ASDAS/Bath Ankyslosing Spondylitis Disease Activity Index, BASDAI). The nurse trained patients to collect, calculate and report (monthly) ASDAS/BASDAI. Treatment allocation was by random allocation to this program or a comorbidities assessment (not presented here and considered here as the control group). RESULTS: A total of 502 patients (250 and 252 in the active and control groups, respectively) were enrolled (age: 46.7 (12.2) years, male gender: 62.7%, disease duration: 13.7 (11.0) years). After the one-year follow-up period, the adherence to the self-assessment program was considered good (i.e. 79% reported scores >6 times). Despite a lack of statistical significance in the primary outcome (e.g. coping) there was a statistically significant difference in favor of this program for the following variables: change in BASDAI, number and duration of the home exercises in the active group, and physical activity (international physical activity score, IPAQ). CONCLUSION: This study suggests a short-term benefit of a nurse-led program on self-management and self-assessment for disease activity in a young axial spondyloarthritis population in terms of disease activity, exercises and physical activity.

Vagal Nerve Stimulation-Modulation of the Anti-Inflammatory Response and Clinical Outcome in Psoriatic Arthritis or Ankylosing Spondylitis.

OBJECTIVES: The vagal nerve exerts an essential pathway in controlling the cholinergic anti-inflammatory reflex. Thus, the study is aimed at investigating the acute effect of a noninvasive transcutaneous vagus nerve stimulation on clinical disease activity and systemic levels of inflammation in patients with psoriatic arthritis or ankylosing spondylitis. METHODS: Twenty patients with psoriatic arthritis (PsA) and 20 patients with ankylosing spondylitis (AS) were included and stimulated bilaterally with a handheld vagal nerve stimulator for 120 seconds 3 times a day for 5 consecutive days. All patients were in remission. Cardiac vagal tone, clinical scores, CRP, and cytokine levels were assessed. RESULTS: In PsA and AS, decreased heart rate was observed, confirming compliance. Furthermore, in PsA, a clear reduction of clinical disease activity associated with a 20% reduction in CRP was shown. In AS, a reduction in interferon-γ, interleukin- (IL-) 8, and 10 was shown. No side effects were described. CONCLUSION: This open-label study provides support for an anti-inflammatory effect of transcutaneous vagus nerve stimulation in patients with psoriatic arthritis and ankylosing spondylitis. The modulated immune response and reduced disease activity and CRP-levels raise the fascinating possibility of using neuromodulation as an add-on to existing pharmacological treatments.

Coincident remission of ankylosing spondylitis after autologous stem cell transplantation for multiple myeloma.

INTRODUCTION: Ankylosing spondylitis is an autoimmune disease with chronic inflammation of the spine and sacroiliac joints that is commonly treated with immunosuppressants including disease-modifying antirheumatic drugs and anti-tumor necrosis factor alpha therapy. CASE REPORT: A 75-year-old female with active ankylosing spondylitis on treatment with etanercept was referred to us for newly diagnosed IgG kappa free light chain multiple myeloma. After failing induction with revlimid, bortezomib, and dexamethasone, she was initiated on carfilzomib. Following the achievement of adequate response to induction, she underwent an autologous hematopoietic stem cell transplant selected for CD34+ cells with melphalan 200mg/m2 conditioning regimen. Given high-risk cytogenetics, i.e. monosomy 17 (17p) and hypodiploidy, she received two cycles of carfilzomib consolidation post-transplant. The patient tolerated the transplant well with successful engraftment and achieved complete remission of multiple myeloma with no detectable M spike, negative immunofixation study, and normalization of light chain ratio. While being off etanercept since the transplant, she noticed complete relief from joint pains related to her ankylosing spondylitis without a need to use the pain-relieving medications.Management and outcome: The patient has sustained remission of ankylosing spondylitis for two years post-transplant without flares or symptoms. She continues to remain off immunosuppressants. DISCUSSION: Although our patient had a coincident and unprecedented resolution of ankylosing spondylitis after receiving the hematopoietic stem cell transplant, this case consolidates the idea of transplant as a potential treatment option for ankylosing spondylitis and other rheumatological conditions.