Diagnostic accuracy of HPV16 early antigen serology for HPV-driven oropharyngeal cancer is independent of age and sex.

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.

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.

Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries.

OBJECTIVES: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. RESULTS: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.

Introducing New GRAPPA Projects.

Every year at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, new project ideas are presented and discussed with a view to obtaining feedback and support. Arising from previous work, a project proposal was presented at the 2023 meeting; the project aims to improve early diagnosis of psoriatic arthritis (PsA) by comparing a physician-based vs a patient questionnaire-based approach. This project has received the backing of the GRAPPA research committee, but additional funding will be required. A second project, approved by GRAPPA, was presented on delivering an epidemiology training module before the GRAPPA annual meeting in 2024, which will target both established GRAPPA clinicians and trainees. Attendance at such a module would enhance the quality of research in psoriatic disease.

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.

Patients with axial spondyloarthritis reported willingness to use remote care and showed high adherence to electronic patient-reported outcome measures: an 18-month observational study.

Remote monitoring using electronic patient reported outcomes (ePROs) in axial spondyloarthritis (axSpA) may improve self-management and reduce the need for consultations. However, knowledge regarding patients' willingness to use remote care and adherence to reporting ePROs is scarce. The objective of this study was to assess axSpA patients' willingness to use remote care and adherence to reporting of ePROs. The study was part of a three-armed randomized controlled trial testing digital follow-up strategies (The ReMonit study, NCT: 05031767). AxSpA patients in low disease activity were randomized to usual care, remote monitoring, or patient-initiated care. Demographics, clinical data, and patients' willingness to use remote care were collected at baseline. EPROs were reported either monthly or quarterly by the remote monitoring- and patient-initiated care group over 18 months, respectively. Adherence to reporting was calculated as number of ePROs completed divided by the total number requested. Mixed model logistic regression was utilized to assess factors associated with adherence to reporting of ePROs. In total 242 patients (median age 43 years, 75% males) were included. The majority (96%) reported high willingness to use remote care. Adherence to reporting ePROs remained high over 18 months by remote monitoring and patient-initiated care groups [median (IQR): 88% (77-100) vs. 83% (66-100)]. No patient characteristics were significantly associated with adherence to reporting of ePROs. The high degree of willingness and adherence to reporting ePROs over time indicates that the majority of axSpA patients with low disease activity are motivated to use remote care.

A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers.

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

Cost-effectiveness of cognitive behavioural and personalized exercise interventions for reducing fatigue in inflammatory rheumatic diseases.

OBJECTIVES: To estimate the cost-effectiveness of a cognitive behavioural approach (CBA) or a personalized exercise programme (PEP), alongside usual care (UC), in patients with inflammatory rheumatic diseases who report chronic, moderate to severe fatigue. METHODS: A within-trial cost-utility analysis was conducted using individual patient data collected within a multicentre, three-arm randomized controlled trial over a 56-week period. The primary economic analysis was conducted from the UK National Health Service (NHS) perspective. Uncertainty was explored using cost-effectiveness acceptability curves and sensitivity analysis. RESULTS: Complete-case analysis showed that, compared with UC, both PEP and CBA were more expensive [adjusted mean cost difference: PEP £569 (95% CI: £464, £665); CBA £845 (95% CI: £717, £993)] and, in the case of PEP, significantly more effective [adjusted mean quality-adjusted life year (QALY) difference: PEP 0.043 (95% CI: 0.019, 0.068); CBA 0.001 (95% CI: -0.022, 0.022)]. These led to an incremental cost-effectiveness ratio (ICER) of £13 159 for PEP vs UC, and £793 777 for CBA vs UC. Non-parametric bootstrapping showed that, at a threshold value of £20 000 per QALY gained, PEP had a probability of 88% of being cost-effective. In multiple imputation analysis, PEP was associated with significant incremental costs of £428 (95% CI: £324, £511) and a non-significant QALY gain of 0.016 (95% CI: -0.003, 0.035), leading to an ICER of £26 822 vs UC. The estimates from sensitivity analyses were consistent with these results. CONCLUSION: The addition of a PEP alongside UC is likely to provide a cost-effective use of health care resources.

Risk factors for head and neck cancer in more and less developed countries: Analysis from the INHANCE consortium.

OBJECTIVE: We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries. SUBJECTS AND METHODS: The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared. RESULTS: The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (<45 years) or female differed by country type for some HNC subsites. CONCLUSION: These findings suggest the degree of industrialization and economic development affects the relationship between smoking and alcohol with head and neck cancer.

EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome.

OBJECTIVE: To develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). METHODS: Following European League against Rheumatism (EULAR) standardised procedures, a multidisciplinary task force formulated recommendations for CVR prediction and management based on systematic literature reviews and expert opinion. RESULTS: Four overarching principles emphasising the need of regular screening and management of modifiable CVR factors and patient education were endorsed. Nineteen recommendations (eleven for gout, vasculitis, SSc, MCTD, myositis, SS; eight for SLE, APS) were developed covering three topics: (1) CVR prediction tools; (2) interventions on traditional CVR factors and (3) interventions on disease-related CVR factors. Several statements relied on expert opinion because high-quality evidence was lacking. Use of generic CVR prediction tools is recommended due to lack of validated rheumatic diseases-specific tools. Diuretics should be avoided in gout and beta-blockers in SSc, and a blood pressure target <130/80 mm Hg should be considered in SLE. Lipid management should follow general population guidelines, and antiplatelet use in SLE, APS and large-vessel vasculitis should follow prior EULAR recommendations. A serum uric acid level <0.36 mmol/L (<6 mg/dL) in gout, and disease activity control and glucocorticoid dose minimisation in SLE and vasculitis, are recommended. Hydroxychloroquine is recommended in SLE because it may also reduce CVR, while no particular immunosuppressive treatment in SLE or urate-lowering therapy in gout has been associated with CVR lowering. CONCLUSION: These recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases.

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.

Research Recommendations Following the Discovery of Pain Sensitizing IgG Autoantibodies in Fibromyalgia Syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is the most common chronic widespread pain condition in rheumatology. Until recently, no clear pathophysiological mechanism for fibromyalgia had been established, resulting in management challenges. Recent research has indicated that serum immunoglobulin Gs (IgGs) may play a role in FMS. We undertook a research prioritisation exercise to identify the most pertinent research approaches that may lead to clinically implementable outputs. METHODS: Research priority setting was conducted in five phases: situation analysis; design; expert group consultation; interim recommendations; consultation and revision. A dialogue model was used, and an international multi-stakeholder expert group was invited. Clinical, patient, industry, funder, and scientific expertise was represented throughout. Recommendation-consensus was determined via a voluntary closed eSurvey. Reporting guideline for priority setting of health research were employed to support implementation and maximise impact. RESULTS: Arising from the expert group consultation (n = 29 participants), 39 interim recommendations were defined. A response rate of 81.5% was achieved in the consensus survey. Six recommendations were identified as high priority- and 15 as medium level priority. The recommendations range from aspects of fibromyalgia features that should be considered in future autoantibody research, to specific immunological investigations, suggestions for trial design in FMS, and therapeutic interventions that should be assessed in trials. CONCLUSIONS: By applying the principles of strategic priority setting we directed research towards that which is implementable, thereby expediating the benefit to the FMS patient population. These recommendations are intended for patients, international professionals and grant-giving bodies concerned with research into causes and management of patients with fibromyalgia syndrome.

UK healthcare services for people with fibromyalgia: results from two web-based national surveys (the PACFiND study).

BACKGROUND: The UK's "Getting It Right First Time" programme recommends that management of people with fibromyalgia should centre on primary care. However, it remains unclear as to how best to organise health systems to deliver services to optimise patient outcomes. AIM: To profile UK healthcare services for people with fibromyalgia: provision of National Health Services (NHS) and use of non-NHS services by people with fibromyalgia. METHODS: Two online open surveys (A and B) incorporating questions about diagnosis, treatment and management of fibromyalgia and gaps in healthcare services were conducted between 11th September 2019 and 3rd February 2020. These were targeted to NHS healthcare professionals consulting with people with fibromyalgia (Survey A) and people ≥16 years diagnosed with fibromyalgia using non-NHS services to manage their condition (Survey B). Descriptive statistics were used to report quantitative data. Thematic analysis was undertaken for qualitative data. RESULTS: Survey A received 1701 responses from NHS healthcare professionals across the UK. Survey B received 549 responses from people with fibromyalgia. The results show that NHS services for people with fibromyalgia are highly disparate, with few professionals reporting care pathways in their localities. Diagnosing fibromyalgia is variable among NHS healthcare professionals and education and pharmacotherapy are mainstays of NHS treatment and management. The greatest perceived unmet need in healthcare for people with fibromyalgia is a lack of available services. From the pooled qualitative data, three themes were developed: 'a troublesome label', 'a heavy burden' and 'a low priority'. Through the concept of candidacy, these themes provide insight into limited access to healthcare for people with fibromyalgia in the UK. CONCLUSION: This study highlights problems across the NHS in service provision and access for people with fibromyalgia, including several issues less commonly discussed; potential bias towards people with self-diagnosed fibromyalgia, challenges facing general practitioners seeking involvement of secondary care services for people with fibromyalgia, and a lack of mental health and multidisciplinary holistic services to support those affected. The need for new models of primary and community care that offer timely diagnosis, interventions to support self-management with access to specialist services if needed, is paramount.

Maintaining musculoskeletal health using a behavioural therapy approach: a population-based randomised controlled trial (the MAmMOTH Study).

OBJECTIVE: Cognitive-behavioural therapy (CBT) has been shown to be effective in the management of chronic widespread pain (CWP); we now test whether it can prevent onset among adults at high risk. METHODS: A population-based randomised controlled prevention trial, with recruitment through UK general practices. A mailed screening questionnaire identified adults at high risk of CWP. Participants received either usual care (UC) or a short course of telephone CBT (tCBT). The primary outcome was CWP onset at 12 months assessed by mailed questionnaire. There were seven secondary outcomes including quality of life (EuroQol Questionnaire-five dimensions-five levels/EQ-5D-5L) used as part of a health economic assessment. RESULTS: 996 participants were randomised and included in the intention-to-treat analysis of which 825 provided primary outcome data. The median age of participants was 59 years; 59% were women. At 12 months there was no difference in the onset of CWP (tCBT: 18.0% vs UC: 17.5%; OR 1.05; 95% CI 0.75 to 1.48). Participants who received tCBT were more likely to report better quality of life (EQ-5D-5L utility score mean difference 0.024 (95% CI 0.009 to 0.040)); and had 0.023 (95% CI 0.007 to 0.039) more quality-adjusted life-years at an additional cost of £42.30 (95% CI -£451.19 to £597.90), yielding an incremental cost-effectiveness ratio of £1828. Most secondary outcomes showed significant benefit for the intervention. CONCLUSIONS: A short course of tCBT did not prevent onset of CWP in adults at high risk, but improved quality of life and was cost-effective. A low-cost, short-duration intervention benefits persons at risk of CWP. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02668003).

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.

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.

Association between comorbidities and disease activity in axial spondyloarthritis: results from the BSRBR-AS.

OBJECTIVE: Whether comorbidities influence disease activity assessment in axial SpA (axSpA) is unclear. Comorbidities inflate DAS28 in rheumatoid arthritis through the patient global score. We examined whether axSpA disease activity measures are differentially affected, and whether comorbidities inflate the AS disease activity score (ASDAS) through the patient global component. METHODS: We used baseline data from the British Society for Rheumatology Biologics Register for AS, including 14 physician diagnosed comorbidities. Linear models were used to compare disease activity (BASDAI, spinal pain, ASDAS) and ESR/CRP according to comorbidity count, adjusted for age, gender, BMI, smoking, socioeconomic status, and education. The same models were used to examine whether the patient global score was associated with comorbidities, additionally adjusting for other ASDAS components. RESULTS: The number of participants eligible for analysis was 2043 (67% male, mean age 49 years); 44% had at least one comorbidity. Each additional comorbidity was associated with higher BASDAI by 0.40 units (95% CI: 0.27, 0.52) and spinal pain by 0.53 (95% CI: 0.37, 0.68). Effect size for ASDAS (0.09 units; 95% CI: 0.03, 0.15) was not clinically significant. ESR and CRP were not associated with comorbidity count. Depression, heart failure and peptic ulcer were consistently associated with higher disease activity measures, but not CRP/ESR. Patient global was associated with comorbidity count, but not independently of other ASDAS components (P = 0.75). CONCLUSION: Comorbidities were associated with higher patient reported disease activity in axSpA. Clinicians should be mindful of the potential impact of comorbidities on patient reported outcome measures and consider additionally collecting ASDAS when comorbidities are present.

Comorbidity and response to TNF inhibitors in axial spondyloarthritis: longitudinal analysis of the BSRBR-AS.

OBJECTIVE: Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but their association with response to TNF inhibitors (TNFi) is unclear. We examined associations between comorbidity history at TNFi initiation and: (i) change in disease indices over time; (ii) binary response definitions; and (iii) time to treatment discontinuation. METHODS: We studied participants starting their first TNFi from a national axSpA register. Comorbidity categories were created from 14 physician-diagnosed conditions and compared against: change in disease indices over time using linear mixed effects models; BASDAI50/2 (50% or 2-unit reduction) and BASDAI < 4 at 6 months using logistic models; and time to treatment discontinuation using Cox models. Models were adjusted for age, gender, BMI, deprivation and education. RESULTS: In total, 994 were eligible for analysis (68% male, mean age 45 years); 21% had one comorbidity and 11% had ≥2. Baseline disease severity was higher in those with comorbidities across all indices, but absolute improvement over time was comparable for BASDAI and spinal pain. Participants with ≥2 comorbidities had smaller absolute improvement in BASFI and quality of life. This group also had numerically reduced odds of achieving BASDAI50/2 [odds ratio (OR) 0.81; 95% CI: 0.45, 1.45] and BASDAI < 4 (OR 0.57; 95% CI: 0.32, 1.04). Treatment discontinuation was increased in those with two comorbidities [hazard ratio (HR) 1.32; 95% CI: 0.88, 2.00] and ≥3 comorbidities (HR 2.18; 95% CI: 1.20, 3.93) compared with none. CONCLUSIONS: Participants with multiple comorbidities had poorer treatment outcomes, particularly increased treatment discontinuation and poorer improvements in function and quality of life. These results inform clinicians and educate patients about response to the first TNFi given comorbidity burden.

The effect of COVID-19 public health restrictions on the health of people with musculoskeletal conditions and symptoms: the CONTAIN study.

OBJECTIVE: To quantify the change in quality of life, disease-specific indicators, health and lifestyle before and during the COVID-19 pandemic among people with musculoskeletal diagnoses and symptoms. METHODS: We undertook an additional follow-up of two existing UK registers involving people with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) and participants in a trial in the UK who had regional pain and were identified at high risk of developing chronic widespread pain. Participants completed the study questionnaire between July and December 2020, throughout which time there were public health restrictions in place. RESULTS: The number of people taking part in the study was 1054 (596 axSpA, 162 PsA, 296 regional pain). In comparison with their previous (pre-pandemic) assessment, there was an age-adjusted significant, small decrease in quality of life measured by EQ-5D [-0.020 (95% CI -0.030, -0.009)] overall and across all population groups examined. This was primarily related to poorer mental health and pain. There was a small increase in fibromyalgia symptoms, but a small decrease in sleep problems. There was a small deterioration in axSpA disease activity, and disease-specific quality of life and anxiety in PsA participants. Predictors of poor quality of life were similar pre- and during the pandemic. The effect of lockdown on activity differed according to age, gender and deprivation. CONCLUSION: Important lessons include focusing on addressing anxiety and providing enhanced support for self-management in the absence of normal health care being available, and awareness that all population groups are likely to be affected.

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.