Treat to target in axial spondyloarthritis: From its concept to its implementation.

Treat to target is defined by a process defining a level of a relevant outcome of the disease to be reached in order to prevent subsequent disability The benefit of a Treat to Target strategy has been clearly demonstrated in chronic diseases such as diabetes and hypertension. A better knowledge of the natural history of chronic inflammatory rheumatic diseases including axial spondyloarthritis has emphasized the deleterious long term effect of a sustained inflammation, usually evaluated by disease activity markers. The Treat to Treat strategy in axial spondyloarthritis has emerged since the possibility of getting treatments not only capable to improve the current symptomatic situation of the patient but also to prevent further deleterious irreversible hard endpoints such as disability due to structural damage or important comorbidities such as renal failure or cardiovascular diseases. This is particularly the case for the "conventional" biologics (e.g. TNF blockers) with an experience in daily practice for at least two decades but also for more recent biologics (e.g. anti IL17 inhibitors) and for some promising targeted synthetic Disease Modifying AntiRheumatics Drugs (e.g. JAK kinase inhibitors) moreover, a part from the abrogation of inflammation, other targets can be considered such as smoking cessation, NSAID intake reduction or treatment of predisposing factors of cardiovascular diseases (e. g. hypertension, …). A Treat to Target strategy in axial spondyloarthritis has to consider the following different components:the stages of the disease, the risks of the disease, the reversible predisposing factors of the risks of the disease, the optimal threshold of the outcome measures evaluating the predisposing factors (TARGET), the time to reach the target and the necessity to maintain this success (sustainability). Moreover, the different methods/initiatives facilitating the implementation of a Treat to Target strategy in rheumatological daily practice have also to be considered (level of evidence, international recommendations, importance of the patient's participation, …).

Non-radiographic versus radiographic axSpA: what's in a name?

Axial spondyloarthritis is a heterogeneous inflammatory condition with variable clinical presentations and outcomes. The complexity of its diagnosis and absence of biomarkers hamper the development of diagnostic criteria with the risk of misuse of the available classification criteria in clinical practice and its consequences. Axial spondyloarthritis should be regarded as a continuum in which some patients, but not all, will have a more severe phenotype characterized by progression into new bone formation and joint fusion. Growing understanding of the factors that might drive disease progression and treatment response will allow for better characterization of treatment options and outcome for each affected individual. The aim of this review is to update the current evidence of what is axial spondyloarthritis and to highlight the need to focus on the concept rather than its classification.

[Evidence-based recommendations on diagnostics and therapy of axial spondyloarthritis : S3 guidelines of the German Society of Rheumatology (DGRh) in cooperation with the Association of the Scientific Medical Societies in Germany (AWMF)]. / Evidenzbasierte Empfehlung zur Diagnostik und Therapie der axialen Spondyloarthritis : S3-Leitlinie der Deutschen Gesellschaft für Rheumatologie (DGRh) in Kooperation mit der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF).

The clinical course of axial spondyloarthritis (SpA) is variable and characterized by chronic back pain and extraspinal manifestations, such as asymmetrical arthritis, dactylitis and enthesitis. Extra-articular manifestations in the eyes (anterior uveitis), skin (psoriasis) and intestines (chronic inflammatory bowel disease) are also frequent manifestations in patients with SpA. Due to the heterogeneity of disease manifestations and the partial concentration on structural alterations in the sacroiliac joints visible in X­ray images, the diagnosis is often delayed for many years. An important step in the direction of improved early recognition of axial SpA was establishment of the Assessment of SpondyloArthritis International Society (ASAS) classification criteria published in 2009, which focused on the initally deep-seated back pain and chronicity in relatively young patients as well as the importance of magnetic resonance imaging and HLA B 27 determination in the early stages of the disease. In order to achieve the foundations for an effective and timely therapy of affected patients, in 2014 on the initiative of the German Society of Rheumatology, S3 guidelines on axial SpA including Bechterew's disease and early forms were formulated in cooperation with other specialist societies. This article gives an overview of the contents of the S3 guidelines on axial SpA.

[Treat-to-target (T2T) recommendation for patients with spondyloarthritis - translation into German]. / "Treat-to-target (T2T)" Empfehlungen für die Behandlung von Patienten mit Spondyloarthritis ­ Übersetzung ins Deutsche.

The management of patients with spondyloarthritis (SpA) has experienced a paradigm shift in recent years. This is true for the treatment of axial as well as peripheral manifestations. International treat to target (T2T) recommendations for SpA based on the T2T strategy have now also been published, which contain 5 higher level principles (A-E) in addition to the 15 recommendations. In order to make the recommendations known and to promote national distribution, German experts have now issued a translation of the T2T recommendations for SpA into German.

EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice.

A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.

Gout in the Spine: Imaging, Diagnosis, and Outcomes.

Gout is characterized by the deposition of monosodium urate crystals and by acute and chronic inflammation in response to crystals so deposited. Multiple case reports and series describe the deposition of monosodium urate in the spine as a rare manifestation of gout, but the actual prevalence of spinal involvement is unknown and likely to be higher than generally anticipated. Here we review the characteristics of 131 previously reported cases of spinal involvement in gout. We focus in particular on the use of imaging modalities and the extent to which they correlate with presenting symptoms and tissue diagnoses. The recent innovation of using dual-energy computerized tomography to identify urate crystal deposition holds promise for reducing the need for surgical intervention and for establishing a true prevalence rate for spinal gout.

[Pain management in chronic pancreatitis and chronic inflammatory bowel diseases]. / Schmerztherapie bei chronischer Pankreatitis und chronisch-entzündlichen Darmerkrankungen.

Apart from local inflammation and defects in secretion, central mechanisms are important for pain etiology in chronic pancreatitis. Therefore, centrally acting co-analgetic agents can be used in addition to classical pain medications. Endoscopic interventions are preferred in patients with obvious dilation of the pancreatic duct. Surgical interventions are generally more effective although they are usually reserved for patients with prior failure of conservative treatment. Diverse surgical options with different efficacies and morbidities are used in individual patients.One of the main problems in chronic inflammatory bowel diseases is abdominal pain. Primarily the underlying disease needs to be adequately treated. Symptomatic pain management will most likely include treatment with acetaminophen and tramadol as well as occasionally principles of a multimodal pain regimen. For the treatment of arthralgia as well as enteropathy-associated arthritis the same treatment options are available as for other spondyloarthritic disorders.

Assessing and Optimizing Large Language Models on Spondyloarthritis Multi-Choice Question Answering: Protocol for Enhancement and Assessment.

BACKGROUND: Spondyloarthritis (SpA), a chronic inflammatory disorder, predominantly impacts the sacroiliac joints and spine, significantly escalating the risk of disability. SpA's complexity, as evidenced by its diverse clinical presentations and symptoms that often mimic other diseases, presents substantial challenges in its accurate diagnosis and differentiation. This complexity becomes even more pronounced in nonspecialist health care environments due to limited resources, resulting in delayed referrals, increased misdiagnosis rates, and exacerbated disability outcomes for patients with SpA. The emergence of large language models (LLMs) in medical diagnostics introduces a revolutionary potential to overcome these diagnostic hurdles. Despite recent advancements in artificial intelligence and LLMs demonstrating effectiveness in diagnosing and treating various diseases, their application in SpA remains underdeveloped. Currently, there is a notable absence of SpA-specific LLMs and an established benchmark for assessing the performance of such models in this particular field. OBJECTIVE: Our objective is to develop a foundational medical model, creating a comprehensive evaluation benchmark tailored to the essential medical knowledge of SpA and its unique diagnostic and treatment protocols. The model, post-pretraining, will be subject to further enhancement through supervised fine-tuning. It is projected to significantly aid physicians in SpA diagnosis and treatment, especially in settings with limited access to specialized care. Furthermore, this initiative is poised to promote early and accurate SpA detection at the primary care level, thereby diminishing the risks associated with delayed or incorrect diagnoses. METHODS: A rigorous benchmark, comprising 222 meticulously formulated multiple-choice questions on SpA, will be established and developed. These questions will be extensively revised to ensure their suitability for accurately evaluating LLMs' performance in real-world diagnostic and therapeutic scenarios. Our methodology involves selecting and refining top foundational models using public data sets. The best-performing model in our benchmark will undergo further training. Subsequently, more than 80,000 real-world inpatient and outpatient cases from hospitals will enhance LLM training, incorporating techniques such as supervised fine-tuning and low-rank adaptation. We will rigorously assess the models' generated responses for accuracy and evaluate their reasoning processes using the metrics of fluency, relevance, completeness, and medical proficiency. RESULTS: Development of the model is progressing, with significant enhancements anticipated by early 2024. The benchmark, along with the results of evaluations, is expected to be released in the second quarter of 2024. CONCLUSIONS: Our trained model aims to capitalize on the capabilities of LLMs in analyzing complex clinical data, thereby enabling precise detection, diagnosis, and treatment of SpA. This innovation is anticipated to play a vital role in diminishing the disabilities arising from delayed or incorrect SpA diagnoses. By promoting this model across diverse health care settings, we anticipate a significant improvement in SpA management, culminating in enhanced patient outcomes and a reduced overall burden of the disease. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57001.

Diagnostic delay in axial spondylarthritis: A lost battle?

Diagnostic delay in axial spondylarthritis (axSpA) remains an unacceptable worldwide problem; with evidence suggesting significant detrimental impact both clinically on the individual, and economically on society. There is therefore, a need for global action across various healthcare professions that come into contact with patients living, and suffering, with undiagnosed axSpA. Recent estimates of the median diagnostic delay suggest that globally, individuals with axSpA wait between 2 and 6 years for a diagnosis - revealing a clear benchmark for improvement. This timespan presents a window of opportunity for earlier diagnosis and intervention, which will likely improve patient outcomes. This review describes the current diagnostic delay as estimated across countries and over time, before presenting evidence from published strategies that may be implemented to improve this delay across primary and secondary care, including for specialties treating extra-musculoskeletal manifestations of axSpA (ophthalmology, gastroenterology, dermatology). Ongoing campaigns tackling delayed diagnosis in axSpA are also highlighted.

The impact of gender and sex on diagnosis, treatment outcomes and health-related quality of life in patients with axial spondyloarthritis.

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic condition, historically considered a predominantly male disease. However, increasing evidence suggests a more equal prevalence between men and women. Of the limited research conducted to date, it is apparent that gender differences exist in terms of time to diagnosis, treatment outcomes and health-related quality of life (HRQoL). Despite this, women are underrepresented in clinical trials and most studies do not stratify by gender to identify potential differences in terms of disease manifestations and treatment response. In this perspectives article, we reflect on the potential biological and social factors contributing to these differences and propose three key areas of education and research that should be prioritised in order to address the unmet needs of female patients with axSpA, namely: (1) to identify ways to increase awareness of disease occurrence in female patients among healthcare professionals (HCPs), (2) to improve understanding of gender differences in disease manifestation and outcomes, and (3) to conduct gender-stratified clinical trials with a representative sample of female patients.

Facilitators of and barriers to implementing a traditional Chinese medicine collaborative model of care for axial spondyloarthritis: a qualitative study.

BACKGROUND: Conventional therapy may be inadequate for many patients with axial spondyloarthritis (axSpA). Traditional Chinese medicine (TCM) may be a viable alternative, but its effectiveness for axSpA is unknown. We are currently conducting a pragmatic randomised controlled trial (RCT) to investigate the effectiveness of a TCM collaborative model of care (TCMCMC), which combines usual rheumatologic care with acupuncture for patients with axSpA. This nested qualitative sub-study aims to identify facilitators of and barriers to the implementation of the TCMCMC. METHODS: We conducted individual in-depth interviews with participants who had completed the acupuncture regimen to elicit opinions on the facilitators of and barriers to the implementation of the TCMCMC. The interviews were transcribed and analysed using thematic analysis. RESULTS: Twelve participants were included, with data saturation occurring after 10 interviews. The analysis revealed both a number of important 'facilitators' and 'barriers'. Facilitators to the implementation of the TCMCMC included effectiveness of TCM to relieve symptoms, inadequacy of conventional treatment and positive social perceptions of TCM. Barriers included scepticism towards TCM, inability of TCM to provide instant relief, needle-related discomfort, variable effectiveness of TCM influenced by physicians' skills and experience and the high cost of TCM. Recommendations to overcome barriers included further patient education about TCM. CONCLUSION: Policymakers should take into account the various feasibility factors identified in this study when developing and implementing a TCMCMC. TRIAL REGISTRATION NUMBER: NCT03420404 (ClinicalTrials.gov).

The journey of the non-radiographic axial spondyloarthritis patient: the perspective of professionals and patients.

OBJECTIVE: Explore the perspective of patients and professionals regarding non-radiographic axial spondyloarthritis (nr-axSpA) and to define the patient's journey from diagnosis to treatment in order to identify unmet needs during the process. METHODS: A qualitative study was carried out in two phases. In the first part, five focus groups were held with rheumatologists, orthopaedist, physiotherapists, primary care physicians (PCP), radiologists and six narrative interviews with nr-axSpA patients. In the second part, a nominal group meeting was held to detect which needs were not covered in the nr-axSpA (all of whom had collaborated in the previous phase). RESULTS: The topics discussed with professional groups and patients were the appropriateness of the term and concept of nr-axSpA, the management of low back pain and inflammatory back pain in routine clinical practice, complementary test and the problem of waiting lists and finally the unmet needs both from a practitioner's and a patient's perspective. The final group explored solutions to the problems based on what was discussed in the first part of the project. Some of these solutions were strengthening relations between specialties, implementing high resolution consultations, rethinking the disability scales, offering better information to patients, designing resource maps and using different strategies to promote knowledge of the disease. CONCLUSION: Many different perspectives on the same disease have revealed the difficult journey of the patient with suspected nr-axSpA, while identifying problems and solutions. Key Points • Diagnosis of nr-AxSpA among health professionals outside rheumatology may lead to numerous turns and difficulties in the patient's journey. • The impact of delays and complications in the journey to diagnosis is not quantified but directly affects the state of well-being and health of patients. • Multidisciplinary care is far from a reality. Primary care (key specialists in any chronic condition), radiologists, orthopaedists, and non-physicians such as physiotherapists and psychologists are generally excluded from dealing with these patients, and often have to do their work outside of physicians, rather than working together in a truly patient-centred medicine.

Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA). METHODS: A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study-specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random-effects models. RESULTS: Twenty-four studies in patients with axial SpA were identified, of which 18 involved tumor necrosis factor inhibitors (TNFi), 8 involved nonsteroidal antiinflammatory drugs (NSAIDs), and 1 involved secukinumab. Spinal radiographic progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), was not significantly different between TNFi-treated and biologics-naive patients at 2 years (mSASSS difference -0.73 [95% confidence interval (95% CI) -1.52, 0.12], I2 = 28%) and ≥4 years (mSASSS difference -2.03 [95% CI -4.63, 0.72], I2 = 63%). Sensitivity analyses restricted to studies with a low risk of bias showed a significant difference in spinal radiographic progression between TNFi-treated and biologics-naive patients at ≥4 years (mSASSS difference -2.17 [95% CI -4.19, -0.15]). No significant difference in spinal radiographic progression was observed between NSAID-treated and control patients (mSASSS difference -0.30 [95% CI -2.62, 1.31], I2 = 71%) or between secukinumab-treated and biologics-naive patients (mSASSS difference -0.34 [95% CI -0.85, 0.17]). With regard to treatment differences in patients with nonradiographic axial SpA or in patients with radiographic progression measured using the sacroiliac joint score, an insufficient number of studies were available for analysis. CONCLUSION: Although no significant protective effect of TNFi treatment on spinal radiographic progression was seen over the course of 2 years or ≥4 years in patients with axial SpA, our analysis restricted to studies with a low risk of bias showed a protective effect of TNFi after ≥4 years. Therefore, long-term TNFi exposure might confer beneficial effects on spinal radiographic progression in axial SpA. No difference in radiographic progression at 2 years was seen in either the NSAID or secukinumab treatment groups compared to their controls. Future studies should explore the effects of biologic treatment on radiographic progression, as well as the effects of long-term biologics exposure, in patients with early axial SpA or those with nonradiographic axial SpA.

Recommendations for the Management of Comorbidity in Patients With Axial Spondyloarthritis in Clinical Practice. / Recomendaciones para el manejo de la comorbilidad en la práctica clínica en pacientes con espondiloartritis axial.

OBJECTIVES: To identify priorities among comorbidities in axial spondyloarthritis (AxSpA) and recommend how to follow them from an eminently practical perspective. METHODS: A multidisciplinary group was selected (10 rheumatologists-six of them experts in AxSpA-, 2 general practitioners, an internist, a cardiologist, a gastroenterologist and a psychologist). In a first discussion meeting, the scope and users were established and a list of comorbidities was voted based on frequency and impact. The panelists had to defend the inclusion of each comorbidity/item in the document with consistent arguments. Four panelists and two methodologists developed systematic reviews on controversial topics. In a second meeting, the results of the reviews and the arguments concerning the items to be included were presented. After the meeting, the final document was drafted. RESULTS: The final document includes two checklists, one for health professionals and another for patients; they incorporate cardiovascular risk, renal comorbidities, gastrointestinal risk, lifestyle, risk of infections and vaccinations, pulmonary involvement, concomitant medication, psycho-affective disorders, osteoporosis, and risk of fracture. In addition, the document reflects the arguments favoring the inclusion of each item and how to record the items for subsequent collection. The panel considered it also appropriate to likewise establish «practices to avoid¼ applicable to comorbidity in AxSpA. CONCLUSIONS: Two checklists and a list of situations to avoid were generated to facilitate the management of comorbidities in AxSpA. In a future step, their utility and acceptance will be tested by a broad group of users that includes doctors, patients and nurses.

Newer therapeutic approaches: spondyloarthritis and uveitis.

Over the last 5 years considerable progress has taken place in the therapeutic approach to spondyloarthritis (SpA). This progress is due in large part to the development of effective biologic therapies and to improved clinical trial design and implementation. This article summarizes treatment advances in SpA with emphasis on the efficacy and safety of biologic agents in the treatment of psoriatic arthritis, ankylosing spondylitis, undifferentiated spondyloarthropathy, and uveitis.

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

OBJECTIVE: To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. RESULTS: In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. CONCLUSION: These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.

Update on the American College of Rheumatology/Spondyloarthritis Research and Treatment Network/Spondylitis Association of America axial spondyloarhtritis treatment guidelines project.

The American College of Rheumatology, the Spondyloarthritis Research and Treatment Network, and the Spondylitis Association of America have begun collaborating on a project to develop treatment guidelines for axial spondyloarthritis. The project will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method, which is based on systematic literature reviews and quantitative evidence summaries, to develop treatment recommendations for the use of pharmacological interventions, rehabilitation, surgery, preventive care, and disease monitoring in patients with ankylosing spondylitis and axial spondyloarthritis.