The prevalence of chronic pain in children and adolescents: a systematic review update and meta-analysis.

ABSTRACT: Chronic pain, defined as persistent or recurring pain or pain lasting longer than 3 months, is a common childhood problem. The objective of this study was to conduct an updated systematic review and meta-analysis on the prevalence of chronic pain (ie, overall, headache, abdominal pain, back pain, musculoskeletal pain, multisite/general pain, and other) in children and adolescents. EMBASE, PubMed, CINAHL, and PsycINFO were searched for publications between January 1, 2009, and June 30, 2023. Studies reporting population-based estimates of chronic nondisease related pain prevalence in children or adolescents (age ≤ 19 years) were included. Two independent reviewers screened articles based on a priori protocol. One hundred nineteen studies with a total of 1,043,878 children (52.0% female, mean age 13.4 years [SD 2.4]) were included. Seventy different countries were represented, with the highest number of data points of prevalence estimates coming from Finland and Germany (n = 19 each, 4.3%). The overall prevalence of chronic pain in children and adolescents was 20.8%, with the highest prevalence for headache and musculoskeletal pain (25.7%). Overall, and for all types of pain except for back pain and musculoskeletal pain, there were significant differences in the prevalence between boys and girls, with girls having a higher prevalence of pain. There was high heterogeneity (I 2 99.9%). Overall risk of bias was low to moderate. In summary, approximately 1 in 5 children and adolescents experience chronic pain and prevalence varies by pain type; for most types, there is higher pain prevalence among girls than among boys. Findings echo and expand upon the systematic review conducted in 2011.

Cut-Offs for Disease Activity States in Axial Spondyloarthritis With Ankylosing Spondylitis Disease Activity Score (ASDAS) Based on C-Reactive Protein and ASDAS Based on Erythrocyte Sedimentation Rate: Are They Interchangeable?

OBJECTIVE: Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. METHODS: We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. RESULTS: In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. CONCLUSION: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

The worldwide prevalence of psoriatic arthritis-a systematic review and meta-analysis.

OBJECTIVES: Previous attempts to pool prevalence studies in PsA have failed to take account of important methodological differences between studies which may have created biased estimates. The aim of this review is to estimate the prevalence of PsA within the adult general population worldwide, considering potential differences between population-based and health administrative studies separately. METHODS: Four electronic databases were systematically searched for articles reporting the prevalence of PsA. Data were pooled to generate worldwide prevalence estimates. Where sufficient data were available, results were summarised by continent. RESULTS: 30 studies were identified, with half from Europe (n = 15). Thirteen population-based studies were identified comprising >92 000 adults, plus 17 studies (>180 million adults) based on health administrative data. The worldwide prevalence of PsA was 112 per 100 000 adults. The prevalence of PsA estimated using populations-based studies was 113 per 100 000 with continent-specific estimates of 207 (Europe), 64 (North America), and 37 (Asia) per 100 000. Health administrative studies gave a global prevalence of 109 per 100 000 with continent-specific prevalence of 175 (Europe), 147 (North America), 78 (Asia), and 17 (South America). CONCLUSION: This review compiles currently available estimates of PsA prevalence in the general population into global and continent-based estimates and considers important study design characteristics. There is wide variability between continents and data in some geographical areas are sparse but available evidence suggests that PsA is more common in Europe and North America compared with Asia and South America, and current best estimates suggest a global prevalence of 112 per 100 000 adults.

Patient-reported outcomes in axial spondyloarthritis and psoriatic arthritis patients treated with secukinumab for 24 months in daily clinical practice.

OBJECTIVES: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates. PATIENTS AND METHODS: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0-10) and Health Assessment Questionnaire (HAQ) ≤0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan-Meier plots with log-rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates. RESULTS: We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24-month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84-1.02]). CONCLUSION: In this large European real-world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders.

Access to Chronic Pain Services for Adults from Minority Ethnic Groups in the United Kingdom (UK): a Scoping Review.

BACKGROUND: Chronic pain services in the UK are required to provide services which meet the diverse needs of patients, but little is known about the access and use of these services by minority ethnic groups. OBJECTIVE: To assess the available evidence regarding the ethnic profile of adults who access secondary and tertiary chronic pain services in the UK. METHODS: A scoping review was conducted (August 2021-October 2021), comprising comprehensive literature searches using Embase, Medline and CINAHL databases and the grey literature. Studies were included if they reported on (i) access to chronic pain services in secondary and/or tertiary care in the UK, (ii) adults and (iii) stated the ethnicity of the involved participants. Studies were included if published between 2004 and 2021, as demographic data during this period would be broadly representative of the UK population, as per the 2021 UK census. A descriptive synthesis of the extracted data was performed. RESULTS: The search yielded 124 records after duplicates were removed. Following title and abstract screening, 44 full texts were screened, ten of which were included in the review. CONCLUSIONS: This is the first review to explore access to chronic pain services for adults from minority ethnic groups in the UK. Given the limited number of studies that met the inclusion criteria, the review highlights the need for routine collection of ethnicity data using consistent ethnic categories within UK chronic pain services and increased involvement of minority ethnic groups within chronic pain research. Findings should inform future research that aims to improve access to UK chronic pain services for adults from minority ethnic groups.

Treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs: British Society for Rheumatology guideline scope.

Pharmacological management has advanced considerably since the 2015 British Society for Rheumatology axial spondyloarthritis (axSpA) guideline to incorporate new classes of biologic DMARDs (bDMARDs, including biosimilars), targeted synthetic DMARDs (tsDMARDs) and treatment strategies such as drug tapering. The aim of this guideline is to provide an evidence-based update on pharmacological management of adults with axSpA (including AS and non-radiographic axSpA) using b/tsDMARDs. This guideline is aimed at health-care professionals in the UK who care directly for people with axSpA, including rheumatologists, rheumatology specialist nurses, allied health professionals, rheumatology specialty trainees and pharmacists; people living with axSpA; and other stakeholders, such as patient organizations and charities.

One-Third of European Patients With Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment.

OBJECTIVE: To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA). METHODS: Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment. RESULTS: Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi. CONCLUSION: Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

Inflammatory Bowel Disease Risk in Patients With Axial Spondyloarthritis Treated With Biologic Agents Determined Using the BSRBR-AS and a MetaAnalysis.

OBJECTIVE: To determine, among patients with axial spondyloarthritis (axSpA), whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic therapies and those treated with other therapies and, specifically, whether the risk is higher in patients treated with etanercept (ETN). METHODS: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) was used to determine the incidence of IBD during follow-up and to calculate the incidence rate difference (IRD) per 1000 person-years (PY), between biologic treatment and other treatment groups. We then conducted a systematic review, involving observational studies and randomized controlled trials (RCTs), to perform a metaanalysis to quantify the difference in incidence of IBD between treatment groups. RESULTS: According to the BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to those who were not exposed to biologic therapy (IRD 11.9, 95% CI 4.3-19.6). This finding was replicated across observational studies but was not seen in placebo-controlled RCTs (IRD 2.2, 95% CI -4.1 to 8.5). Data from the BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to ETN compared to other anti-tumor necrosis factor (TNF) therapies (IRD -6.5, 95% CI -21.3 to 8.5). RCTs and their extensions suggest a small-yet not statistically significant-absolute increased incidence associated with ETN of between 2.1 and 5.8 per 1000 PY compared to other anti-TNF therapies. CONCLUSION: There was an excess risk of IBD among persons treated with biologics in observational studies. Only evidence from RCTs suggested that ETN was associated with an increased risk compared to other anti-TNF therapies, albeit with considerable uncertainty.

Predictors of ASDAS-CRP inactive disease in axial spondyloarthritis during treatment with TNF-inhibitors: Data from the EuroSpA collaboration.

OBJECTIVES: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. METHODS: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. RESULTS: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97-0.98), men vs. women: 1.88 (1.60-2.22), current vs. non-smoking: 0.76 (0.63-0.91), HLA-B27 positive vs. negative: 1.51 (1.20-1.91), TNF start year 2015-2018 vs. 2009-2014: 1.24 (1.06-1.45), CRP>10 vs. ≤10 mg/l: 1.49 (1.25-1.77), one unit increase in health assessment questionnaire (HAQ): 0.77 (0.58-1.03), one-millimeter (mm) increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue and spinal pain: 0.99 (0.99-1.00) and 0.99 (0.99-1.99), respectively CONCLUSION: Common baseline predictors of treatment response and adherence to TNFi could be identified across data from 15 European registries, indicating that they may be universal across different axSpA populations.

Enabling work participation for people with musculoskeletal conditions: lessons from work changes imposed by COVID-19: a mixed-method study.

OBJECTIVES: To understand what we can learn from the impact of the COVID-19 pandemic and lockdown about what enables work participation for people with inflammatory arthritis and chronic pain conditions. DESIGN: Qualitative interviews embedded within an observational questionnaire study of individuals with musculoskeletal (MSK) conditions. SETTING: UK primary care (general practices), and secondary care-based rheumatology services. PARTICIPANTS: Individuals with axial spondyloarthritis, psoriatic arthritis and MSK pain from three established cohorts completed an online/paper-based questionnaire (July-December 2020). A subset of respondents were selected for semistructured interviews. PRIMARY AND SECONDARY OUTCOME MEASURES: The survey quantified the effects of lockdown on work circumstances. Qualitative interviews explored the impacts of these changes and the advantages and disadvantages of changes in work circumstances. RESULTS: 491 people (52% female, median age 49 years) who were employed at the time of lockdown responded to the questionnaire. The qualitative analysis included 157 free-text comments on work from the questionnaire and data collected within 18 interviews.Participants reported impacts on mental and physical health, and significant financial anxieties. The impact of work changes varied depending on individual and home circumstances. Some felt forced to ignore advice to shield and continue working. The flexibility offered by home working and changes in commuting enabled greater physical activity for some, while others missed the exercise normally undertaken as part of their commute. Others reported a constant need to be 'present' online, which heightened anxiety and worsened MSK symptoms. CONCLUSION: Lockdown showed that flexible working arrangements, which consider the positive and negative aspects of commuting, posture, movement, and work environment matter for work participation, and can have wider benefits in terms of health and well-being for those with long-term MSK conditions. Incorporating these into new models of work will help make the workplace more equitable and inclusive for people with long-term MSK conditions.

Lessons from experiences of accessing healthcare during the pandemic for remobilizing rheumatology services: a national mixed methods study.

Objectives: To understand the impact of the coronavirus disease 2019 pandemic on access to healthcare services for patients with inflammatory and non-inflammatory musculoskeletal (MSK) conditions. Methods: Three established cohorts that included individuals with axial SpA, psoriatic arthritis and MSK pain completed a questionnaire between July and December 2020. In parallel, a subset of individuals participated in semistructured interviews. Results: A total of 1054 people (45% female, median age 59 years) were included in the quantitative analyses. Qualitative data included 447 free-text questionnaire responses and 23 interviews. A total of 57% of respondents had tried to access care since the start of the UK national lockdown. More than a quarter reported being unable to book any type of healthcare appointment. General practice appointments were less likely to be delayed or cancelled compared with hospital appointments. Younger age, unemployment/health-related retirement, DMARD therapy, anxiety or depression and being extremely clinically vulnerable were associated with a greater likelihood of attempting to access healthcare. People not in work, those reporting anxiety or depression and poorer quality of life were less likely to be satisfied with remotely delivered healthcare. Participants valued clear, timely and transparent care pathways across primary care and specialist services. While remote consultations were convenient for some, in-person appointments enabled physical assessment and facilitated the development and maintenance of clinical relationships with care providers. Conclusions: We identified patient factors that predict access to and satisfaction with care and aspects of care that patients value. This is important to inform remobilisation of rheumatology services to better meet the needs of patients.

Generating EQ-5D-5L health utility scores from BASDAI and BASFI: a mapping study in patients with axial spondyloarthritis using longitudinal UK registry data.

BACKGROUND: Preference-based health-state utility values (HSUVs), such as the EuroQol five-dimensional questionnaire (EQ-5D-5L), are needed to calculate quality-adjusted life-years (QALYs) for cost-effectiveness analyses. However, these are rarely used in clinical trials of interventions in axial spondyloarthritis (axSpA). In these cases, mapping can be used to predict HSUVs. OBJECTIVE: To develop mapping algorithms to estimate EQ-5D-5L HSUVs from the Bath Ankylosing Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). METHODS: Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) provided 5122 observations with complete BASDAI, BASFI, and EQ-5D-5L responses covering the full range of disease severity. We compared direct mapping using adjusted limited dependent variable mixture models (ALDVMMs) and optional inclusion of the gap between full health and the next feasible value with indirect response mapping using ordered probit (OPROBIT) and generalised ordered probit (GOPROBIT) models. Explanatory variables included BASDAI, BASFI, and age. Metrics to assess model goodness-of-fit and performance/accuracy included Akaike and Bayesian information criteria (AIC/BIC), mean absolute error (MAE) and root mean square error (RMSE), plotting predictive vs. observed estimates across the range of BASDAI/BASFI and comparing simulated data with the original data set for the preferred/best model. RESULTS: Overall, the ALDVMM models that did not formally include the gap between full health and the next feasible value outperformed those that did. The four-component mixture models (with squared terms included) performed better than the three-component models. Response mapping using GOPROBIT (no squared terms included) or OPROBIT (with squared terms included) offered the next best performing models after the three-component ALDVMM (with squared terms). Simulated data of the preferred model (ALDVMM with four-components) did not significantly underestimate uncertainty across most of the range of EQ-5D-5L values, however the proportion of data at full health was underrepresented, likely due in part to model fitting on a small number of observations at this point in the actual data (4%). CONCLUSIONS: The mapping algorithms developed in this study enabled the generation of EQ-5D-5L utilities from BASDAI/BASFI. The indirect mapping equations reported for the EQ-5D-5L facilitate the calculation of the EQ-5D-5L utility scores using other UK and country-specific value sets.

Role of Metrology in Axial Spondyloarthritis: Does It Provide Unique Information in Assessing Patients and Predicting Outcome? Results From the British Society for Rheumatology Biologic Register for Ankylosing Spondylitis.

OBJECTIVE: To determine among patients with axial spondyloarthritis (SpA) the factors associated with decreased spinal mobility and to determine whether poor mobility is a predictor of response to anti-tumor necrosis factor (anti-TNF) therapy. METHODS: This was a prospective UK cohort study of persons meeting Assessment of Spondylarthritis international Society (ASAS) criteria for axial SpA. At recruitment, clinical and patient-reported factors independently associated with spinal mobility (measured by the Bath Ankylosing Spondylitis Metrology Index [BASMI]) were determined. Among those commencing anti-TNF therapy, factors that were independent predictors of response were determined using ASAS criteria, quality of life, and Ankylosing Spondylitis Disease Activity Score (ASDAS) response criteria. RESULTS: A total of 1,960 participants were eligible; 70% were male, the median age was 48 years (interquartile range [IQR] 37, 59), and the median BASMI score 3.6 (IQR 2.2, 5.3). Factors independently associated with poor spinal mobility were poorer function, meeting radiographic criteria for AS, longer symptom duration, higher levels of inflammation (measured by C-reactive protein level), older age, male sex, not being currently employed, and lower levels of education. For 51% of participants, the measured BASMI score was within 1 of that estimated. Poorer mobility (higher BASMI score) was an independent predictor of not meeting response criteria for ASAS 20% improvement (odds ratio [OR] per increasing score 0.80 [IQR 0.66, 0.98]), ASAS 40% improvement (OR 0.69 [IQR 0.50, 0.95]), and quality of life (measured by the Ankylosing Spondylitis Quality of Life Questionnaire) (ß = 0.64 [IQR 0.26, 1.02]), but was not related to meeting ASDAS response criteria. CONCLUSION: The BASMI score was estimated moderately well by other routinely measured factors in patients with axial SpA and was an independent predictor of response to biologic therapy for some, but not all, commonly used measures. Consensus around its role in disease monitoring and clinical decisions, particularly in the likely context of face-to-face consultations becoming less frequent, remains to be established.

Real-World Six- and Twelve-Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries.

OBJECTIVE: There is a lack of real-life studies on interleukin-17 (IL-17) inhibition in psoriatic arthritis (PsA). We assessed real-life 6- and 12-month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries. METHODS: Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care for secondary use. Data were pooled and analyzed with Kaplan-Meier plots, log rank tests, Cox regression, and multiple linear and logistic regression analyses. RESULTS: A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86% and 76% after 6 and 12 months, respectively. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for the 28-joint Disease Activity Index for Psoriatic Arthritis, the Disease Activity Score in 28 joints using the C-reactive protein level, and the Simplified Disease Activity Index (SDAI) were 13%/46% (11%/39%), 36%/55% (30%/46%), and 13%/56% (11%/47%), and 12-month rates were 11%/46% (7%/31%), 39%/56% (26%/38%), and 16%/62% (10%/41%), respectively. Clinical Disease Activity Index remission/LDA rates were similar to the SDAI rates. Six-month American College of Rheumatology 20%/50%/70% improvement criteria responses were 34%/19%/11% (29%/16%/9%); 12-month rates were 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD-naive patients, similar across time since diagnosis (<2/2-4/>4 years), and varied significantly across the European registries. CONCLUSION: In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to that in previous observational studies of tumor necrosis factor inhibitors. Retention, remission, LDA, and response rates were significantly better for b/tsDMARD-naive patients, were independent of time since diagnosis, and varied significantly across the European countries.

European bio-naïve spondyloarthritis patients initiating TNF inhibitor: time trends in baseline characteristics, treatment retention and response.

OBJECTIVES: To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating TNF inhibitor (TNFi) treatment. METHODS: Prospectively collected data on bio-naïve axSpA and PsA patients from routine care in 15 European countries were pooled. Three cohorts were defined according to year of TNFi initiation: A (1999-2008), B (2009-2014) and C (2015-2018). Retention, remission and response rates were assessed at 6, 12 and 24 months. RESULTS: In total, 27 149 axSpA and 17 446 PsA patients were included. Cohort A patients had longer disease duration compared with B and C. In axSpA, cohort A had the largest proportion of male and HLA-B27 positive patients. In PsA, baseline disease activity was highest in cohort A. Retention rates in axSpA/PsA were highest in cohort A and differed only slightly between B and C. For all cohorts, disease activity decreased markedly from 0 to 6 months. In axSpA, disease activity at 24 months was highest in cohort A, where also remission and response rates were lowest. In PsA, remission rates at 6 and 12 months tended to be lowest in cohort A. Response rates were at all time points comparable across cohorts, and less between-cohort disease activity differences were seen at 24 months. CONCLUSION: Our findings indicate that over the past decades, clinicians have implemented more aggressive treatment strategies in spondyloarthritis. This was illustrated by shorter disease duration at treatment initiation, decreased retention rates and higher remission rates during recent years.

The changing states of fibromyalgia in patients with axial spondyloarthritis: results from the British Society of Rheumatology Biologics Register for Ankylosing Spondylitis.

OBJECTIVES: To identify factors associated with FM development and recovery in patients with axial SpA (axSpA). METHODS: The British Society of Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited patients with axSpA from 83 centres in a prospective study. FM was diagnosed using the self-reported Fibromyalgia Survey Diagnostic Criteria from 2015. Measures of axSpA disease activity and clinical findings were recorded at regular intervals. We identified predictors for FM development and recovery between yearly visits using uni- and multivariable logistic regression models. RESULTS: A total of 801 participants, 247 (30.8%) female, had two or more visits and were eligible for inclusion. A total of 686 participants did not have FM at baseline, of whom 45 had developed FM at follow-up, while 115 participants had FM at baseline, of whom 77 had recovered at follow-up. A high baseline BASDAI score [odds ratio (OR) 1.27 (95% CI 1.08, 1.49)] and Widespread Pain Index (WPI) [OR 1.14 (95% CI 1.02, 1.28)] were significantly associated with FM development in the final multivariable model. A low baseline BASFI score [OR 0.68 (95% CI 0.53, 0.86)] and WPI [OR 0.84 (95% CI 0.720, 0.97)] and starting a TNF inhibitor [OR 3.86 (95% CI 1.54, 9.71)] were significantly associated with FM recovery. CONCLUSION: High levels of disease activity and the presence of widespread pain is associated with the development of FM in patients with axSpA, while low levels of the same variables and starting a TNF inhibitor are associated with recovery from FM. The presence of comorbid FM should be considered in patients with persistent high axSpA disease activity and widespread pain.

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.

OBJECTIVE: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. METHODS: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. RESULTS: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively. CONCLUSIONS: PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.

Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration.

BACKGROUND: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. METHODS: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. RESULTS: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. CONCLUSION: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.