Navigating the complexity of pain in psoriatic arthritis and axial spondyloarthritis.

PURPOSE OF REVIEW: Pain is the most common and often most troublesome feature of chronic autoimmune diseases such as psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). A predominant concept is that the main source of pain is from disease-induced tissue inflammation and structural damage, activating peripheral nerve fibers which relay to the central nervous system. This mechanism is nociceptive pain and the presumption has been that controlling inflammation will be sufficient to reduce this form of pain. However, despite control of inflammation, patients may still have significant residual pain. RECENT FINDINGS: We are learning that there are additional pain mechanisms, neuropathic and nociplastic, that are often operative in patients with rheumatologic conditions, that can significantly influence pain experience, quantitation of disease activity, and may benefit from therapeutic approaches distinct from immunotherapy. Neuropathic pain arises from diseased or damaged nerve tissue and nociplastic pain reflects sensitization of the central nervous system due to multiple genetic, neurobiologic, neural network dysregulation, and psychosocial factors. Pain arising from these mechanisms influence assessment of disease activity and thus needs to be factored into decision-making about immunotherapy efficacy. SUMMARY: This review addresses the importance of accurately assessing the complex mechanisms of pain experience in patients with PsA and AxSpA to more appropriately manage immunomodulatory, neuromodulatory, and nonpharmacologic therapies.

Disease modification in axial spondyloarthritis - still a controversy?

PURPOSE OF REVIEW: This review evaluates recent advancements in disease-modifying therapies for axial spondyloarthritis (axSpA). RECENT FINDINGS: A recent study could not demonstrate an additional effect of NSAID therapy on golimumab [Tumor Necrosis Factor-α inhibitor (TNFi)] on structural progression; however, this might be due to the fact that the study was underpowered. While DMARDs have shown promise in suppressing inflammation, their impact on structural progression remains uncertain. A well powered trial showed no difference in spinal progression between secukinumab [Interleukin17A inhibitor (IL17Ai)] and adalimumab-biosimilar (TNFi). Preliminary data on Janus kinase inhibitors (JAKi) focus on MRI findings but lack evidence on radiographic spinal progression. While some studies suggest promising outcomes, others reveal limitations and inconclusive findings. SUMMARY: Recent studies explore the effectiveness of NSAIDs, biological disease-modifying antirheumatic drugs like TNFi and IL-17i, as well as JAK inhibitors in axSpA. Conflicting evidence surrounds these therapies' ability to impede structural progression, with challenges in study design and interpretation. Moreover, changes in demographics and treatment methods underscore the importance of examining trends over time when assessing disease outcomes. Ultimately, ongoing research could benefit from new imaging tools when evaluating therapeutic strategies for modifying disease progression in axSpA.

Sociodemographic and clinical variables associated with negative illness perception in patients newly diagnosed with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis-a survey based cross-sectional study.

When newly diagnosed with inflammatory arthritis (IA), acquiring self-management skills is beneficial, to enhance quality of life. The personal beliefs and mental representations patients hold about their illness, known as illness perception, significantly influence the development of these skills. Recognizing characteristics that affect illness perception is key to identifying patients requiring additional support for the development of self-management skills. This study aimed at identifying the sociodemographic and clinical characteristics associated with a negative illness perception. This cross-sectional study was based on survey data from patients diagnosed for ≤ 2 years. The Brief Illness Perception Questionnaire (B-IPQ) was used to measure illness perception. After psychometric testing, we divided the B-IPQ into two domains: (1) a control domain and (2) a consequence domain. We performed logistic regression analyses with multiple imputations. A total of 1,360 patients (61% females) were included. Among them, 64%, 20%, and 16% were diagnosed with rheumatoid arthritis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), respectively. Younger patients with lower socioeconomic status, a diagnosis of PsA or axSpA, high disease activity (OR 3.026, CI 2.208;4.147), severe physical disability (OR 4.147. CI 2.883;6.007), severe pain (OR 3.034, CI 1.991;4.622), and severe fatigue (OR 2.612, CI 1.942;3.513) were significantly more likely to report having a negative illness perception. Younger patients with a higher symptom burden, increased disease activity, lower socioeconomic status, and a diagnosis of PsA or axSpA may require additional attention and support in rheumatology clinical practice to aid in the development of their self-management skills.

Axial spondyloarthritis.

Axial spondyloarthritis (axSpA) encompasses both radiographic and non-radiographic axSpA. It is a chronic inflammatory disease with a predilection for involving the axial skeleton. The most common presenting symptoms are chronic back pain and spinal stiffness but peripheral and extra-musculoskeletal manifestations occur also frequently. The diagnosis of axSpA relies on the recognition of a clinical pattern of the disease, based on clinical, laboratory and imaging features. The Assessment in SpondyloArthritis international Society classification criteria for axSpA are valid and well implemented for research purposes. Sustained disease activity, measured by validated tools such as the Ankylosing Spondylitis Disease Activity Score, leads to irreversible structural damage and poor functioning and therefore should be abrogated. As part of the management algorithm, non-steroidal anti-inflammatory drugs remain as the first line of pharmacological treatment besides physiotherapy. As a second line, tumour necrosis factor inhibitor and interleukin-17 inhibitor are available but recently Janus kinase inhibitors have also shown efficacy in improving symptoms of the disease.

Targeting the Interleukin-23/Interleukin-17 Inflammatory Pathway: Successes and Failures in the Treatment of Axial Spondyloarthritis.

The IL-23/IL-17 pathway has been implicated in the etiopathogenesis of axial spondyloarthritis through studies of genetic polymorphisms associated with disease, an animal model with over-expression of IL-23 that resembles human disease, and observations that cytokines in this pathway can be found at the site of disease in both humans and animal models. However, the most direct evidence has emerged from clinical trials of agents targeting cytokines in this pathway. Monoclonal antibodies targeting IL-17A have been shown to ameliorate signs and symptoms, as well as MRI inflammation in the spine and sacroiliac joints, in patients with radiographic and non-radiographic axial spondyloarthritis. This was evident in patients refractory to non-steroidal anti-inflammatory agents as well as patients failing treatment with tumor necrosis factor inhibitor therapies. Treatment with a bispecific antibody targeting both IL-17A and IL-17F was also effective in a phase II study. Post-hoc analyses have even suggested a potential disease-modifying effect in reducing development of spinal ankylosis. However, benefits for extra-articular manifestations were limited to psoriasis and did not extend to colitis and uveitis. Conversely, trials of therapies targeting IL-23 did not demonstrate any significant impact on signs, symptoms, and MRI inflammation in axial spondyloarthritis. These developments coincide with recent observations that expression of these cytokines is evident in many different cell types with roles in innate as well as adaptive immunity. Moreover, evidence has emerged for the existence of both IL-23-dependent and IL-23-independent pathways regulating expression of IL-17, potentially associated with different roles in intestinal and axial skeletal inflammation.

Exercise capacity in axial spondyloarthritis and associated factors: A cross-sectional controlled study.

OBJECTIVE: To examine the associations between exercise capacity (EC), cardiovascular (CV) risk factors and disease-related variables in axial spondyloarthritis (AxSpA) patients. METHODS: In this cross-sectional controlled study, CV risk profile data, physical activity, 10-year CV event risk estimated by the Framingham model and Ankylosing Spondylitis Disease Activity Score - C-reactive protein were recorded. A maximal treadmill exercise test by Bruce protocol was administered. Analyses of covariance were performed with adjustments for age, smoking status and physical activity level. Linear regression analysis was performed to study the association between EC and related CV risk factors. RESULTS: Thirty-eight patients and 38 age-gender matched controls were recruited between May and October 2014. Patients had significantly lower EC than controls (MD 2.2; metabolic equivalents 0.91-3.49; P = .001). The difference remained significant after adjustments (P = .001). There were significant correlations between EC and age, 10-year CV event risk, body mass index (BMI) and waist circumference for patients and controls (P < .001 and P < .05, respectively). There was a significant relationship between EC and total cholesterol, triglycerides and heart rate recovery (HRR) in patients (P = .04, P < .001 and P = .006, respectively). High-density lipoprotein - cholesterol was significantly higher, and BMI was significantly lower in nonradiographic AxSpA patients (P = .026 and P = .03 respectively). Age and triglyceride levels were found as the significant predictors for EC in the AxSpa group (for age ß = -.105, P = .003; for triglycerides ß = -.016 P = .003). CONCLUSION: Exercise capacity was significantly lower and attenuated HRR was significantly associated with low EC and high 10-year CV event risk in AxSpA patients.

A single center experience: physician related diagnostic delay and demographic and clinical differences between patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis.

Background. A large number of comparative studies have been conducted for ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA), including disease burden, treatment modalities and patient characteristics. The aim of this study was to compare physician related diagnostic delay time between patients with AS and nr-axSpA. Methods. In our retrospective study we included 266 patients with axSpA. Patients were classified into two subgroups, AS and nr-axSpA. The time from back pain onset until diagnosis of axSpA was defined as the diagnostic delay. The first specialist referred to and the first diagnosis for each patient was noted in detail. Patient characteristics, clinical manifestations and laboratory and imaging results at diagnosis were also compared between subgroups. Results. The diagnostic delay time was significantly longer for AS patients [6 ± 8.14 years vs 1.62 ± 2.54 years]. 40.9% of all patients were initially consulted by specialists in physical therapy and rehabilitation, followed by 29.7% consulted by a neurosurgeon and 19.9% by a rheumatologist. The most common initial diagnosis was fibromyalgia, 52.6% (140), followed by ankylosing spondylitis, 28.9% (77), and lumbar disc hernia, 12.7% (34). Conclusion. The vast majority of patients were initially evaluated by healthcare providers other than rheumatologists and mostly diagnosed with fibromyalgia. Efforts to increase awareness and to educate first healthcare providers may shorten the diagnostic delay time.

Similar biologic drug response regardless of radiographic status in axial spondyloarthritis: data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis registry.

OBJECTIVE: To describe the baseline characteristics, biologic DMARD (bDMARD) response and drug survival of axial SpA (axSpA) patients in the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) according to radiographic status. METHODS: The BSRBR-AS is a national prospective cohort including axSpA participants classified according to the Assessment of SpondyloArthritis international Society criteria. In this analysis, baseline data of patients starting bDMARDs were compared. Ankylosing Spondylitis Disease Activity Scores (ASDASs) for low disease status, clinically important improvement (CII) and major improvement (MI) at 1 year were used to assess treatment response. Cox proportional hazards analysis was performed after adjusting for clinically relevant confounders. RESULTS: A total of 1145 axSpA patients were included. Higher male prevalence, older age and longer disease duration were seen in the radiographic axSpA (r-axSpA) subgroup. Based on a complete case analysis (290 patients), two-thirds of patients achieved an ASDAS low disease state at 1 year regardless of radiographic status [non-radiographic axSpA (nr-axSpA) 64.2% vs r-axSpA 66.1]. No statistically significant differences were seen between the subgroups in attaining ASDAS CII (nr-axSpA 50.7% vs r-axSpA 44.7%) or MI (nr-axSpA 20% vs r-axSpA 18.7%). Drug survival probability curves were similar for both subgroups and the hazard ratio for nr-axSpA/axSpA was 0.94 (95% CI 0.69, 1.28) when adjusted for sex, age, baseline ASDAS with CRP, smoking status, disease duration, HLA-B27 and prescribed biologic. CONCLUSIONS: Although there appeared to be some differences in the baseline characteristics when exploring this cohort according to radiographic status, which are likely related to the natural history of the disease, the level of biologic response and drug survival was comparable between nr-axSpA and r-axSpA.

Quantification of Fat Metaplasia in the Sacroiliac Joints of Patients With Axial Spondyloarthritis by Chemical Shift-Encoded MRI: A Diagnostic Trial.

Objective: To study the diagnostic performance of chemical shift-encoded MRI (CSE-MRI) in the diagnosis of axial spondyloarthritis (axSpA). Methods: CSE-MRI images were acquired for consecutive patients complaining of back pain as well as healthy volunteers. Proton density fat fraction (PDFF) values were measured independently by two readers. Diagnostic performance of CSE-MRI was analyzed by sensitivity analysis and ROC curve analysis. Logistic regression analysis was employed to investigate the risk factors of extensive fat deposition in the SIJs. Results: A total of 52 r-axSpA patients, 37 nr-axSpA patients, 24 non-SpA patients and 34 healthy volunteers were included. Mean PDFF values in the SIJs of patients with r-axSpA and nr-axSpA (72.7% and 64.5%) were significantly higher than non-SpA patients and healthy volunteers (56.0% and 57.6%) (p<0.001). By defining extensive fat deposition in the SIJs as ≥8 ROIs with PDFF values over 70%, its sensitivity and specificity in diagnosing axSpA reached 72.47% and 86.21%%. By joining bone marrow edema (BME) with ≥8 ROIs (PDFF>70%), 22 (24.71%) and 23 (25.84%) more axSpA patients were classified as SIJ MRI (+) by reader 1 and 2, but specificities decreased by 15.52% and 10.34%. Multivariate logistic regression analysis confirmed longer disease duration as the independent risk factor of extensive fat deposition in SIJs (OR=1.15, 95%CI[1.03, 1.32]), while bDMARDs medication was a protective factor (OR=0.15, 95%CI[0.04, 0.51]). Conclusion: CSE-MRI is a reliable tool to quantitively assess the fat metaplasia in the SIJs of axSpA patients. Extensive fat deposition in the SIJs could add incremental diagnostic value to BME, but at the cost of decreased specificities.

The IBIS-Q [IBd Identification of Spondyloarthritis Questionnaire]: A Novel Tool to Detect Both Axial and Peripheral Arthritis in Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Both peripheral and axial spondyloarthritis [SpA] occur in inflammatory bowel disease [IBD] and represent the commonest extra-intestinal manifestation. We aimed to develop an easy and quick questionnaire through psychometric analysis, to identify peripheral and axial SpA in IBD patients within an integrated combined multidisciplinary rheumatological-gastroenterology clinic. METHODS: Initially, SpA-IBD experts generated a 42-item list covering SpA manifestations including spinal, articular, and entheseal involvement. The new questionnaire was administered before routine clinical IBD assessment. On the same day, rheumatological assessment, blinded to both history and questionnaire results, was performed to explore the presence of the Assessment of SpondyloArthritis International Society [ASAS] criteria for SpA, diagnostic criteria for fibromyalgia [FM], and non-specific low back pain [NSLB]. Factorial analysis of questionnaire items to identify the main factors-receiver operating characteristic [ROC] curves for sensitivity/specificity and Youden index for cut-off-were performed. RESULTS: Of the 181 consecutive patients, 56 met the ASAS SpA criteria [prevalence of 30%] with 10 new cases detected [5.5%: seven peripheral and three axial]. Through the psychometric and factorial analysis, we selected 14 items for the final questionnaire [named IBIS-Q]. The IBIS-Q was quick and performed well for detection of axial SpA and peripheral SpA (area under the curve [AUC] 0.88 with 95% confidence interval [CI] 0.830.93). A cut-off of three positive questions had a sensitivity 93% and specificity 77% for SpA patient identification. CONCLUSIONS: The IBIS-Q is a useful and simple tool to use in IBD clinics for SpA detection, with a good statistical performance. Further studies are needed to validate it.

Diagnóstico de espondiloartrite axial em pacientes com fibromialgia / Axial spondyloarthritis diagnosis in fibromyalgia patients

Objetivo: Avaliar pacientes com fibromialgia e dor lombar, bus- cando características clínicas de espondiloatrites axiais. Méto- dos: Neste estudo transversal, cem pacientes com fibromialgia e idades entre 18 e 65 anos foram avaliados. A avaliação consis- tiu em um questionário baseado no braço clínico dos critérios Assessment of Spondyloarthritis International Society para diag- nóstico de espondiloatrites axiais e um questionário de impacto da fibromialgia (Revised Fibromyalgia Impact Questionnaire). Re- sultados: Quando o braço clínico da Assessment of Spondyloar- thritis International Society foi aplicado em pacientes com fibro- mialgia e dor lombar, 80% dos pacientes preencheram os critérios para diagnóstico de espondiloatrites axiais. As principais carac- terísticas de espondiloatrite axial foram dor lombar inflamatória, boa resposta a drogas anti-inflmatórias não esteroidais, artrite e entesite. Pacientes com critérios de espondiloatrites axiais posi- tivos apresentaram maiores níveis séricos de proteína C-reativa (p=0,00035). O valor médio do Revised Fibromyalgia Impact Ques- tionnaire para todos os pacientes avaliados foi 63,6, e não houve di- ferença entre os pacientes que preencheram os critérios e aqueles que não preencheram. Conclusão: Pacientes com fibromialgia e dor lombar frequentemente apresentam características clínicas de espondiloatrite axial, e aqueles que preencheram os crité- rios clínicos para espondiloatrites axiais também apresentaram maiores níveis séricos de proteína C-reativa.

Objective: To evaluate patients with fibromyalgia and back pain for clinical features of axial spondyloarthritis. Methods: In this cross-sectional study, one hundred fibromyalgia patients between 18 and 65 years old were assessed. The assessment consisted of a questionnaire based on the clinical arm ofthe Assessment of Spondyloarthritis International Society criteria for the diagnosis of axial spondyloarthritis and a questionnaire on the impact of fibromyalgia (Revised Fibromyalgia Impact Questionnaire). Re- sults: When the clinical arm of the Assessment of Spondyloarthri- tis International Society was applied in patients with fibromyal- gia and back pain, 80% of the patients met the clinical criteria for diagnosis of axial spondyloarthritis. The main features of axial spondyloarthritis in fibromyalgia patients were inflammatory back pain, good response to non-steroidal anti-inflammatory drugs (NSAIDs), arthritis, and enthesitis. Patients with positive axial spondyloarthritis criteria presented with higher C- reac- tive protein levels (p=0.00035). The mean value of the Revised Fibromyalgia Impact Questionnaire for all patients assessed was 63.6 and there was no difference between patients that met the criteria for axial spondyloarthritis and those who did not. Con- clusion: Patients with fibromyalgia and back pain often present clinical features of axial spondyloarthritis, and those who met the clinical criteria for axial spondyloarthritis also presented with higher levels of C-reactive protein.