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ObjectiveTo 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).MethodsThe 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.ResultsAccording 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.ConclusionThere 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.

Objectives: to describe the driving difficulties experienced by individuals with axial spondyloarthritis (axSpA), and characterise associated clinical and sociodemographic features, and impact on work.Method: the Scotland Registry for Ankylosing Spondylitis (SIRAS) is a cohort study of patients with a clinical diagnosis of axSpA. Baseline information was collected on clinical and patient‐reported measures, and work participation measures (Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI: SHP)). Patient‐rated difficulties with nine driving tasks were used in a factor analysis, and relationships between driving difficulty and work participation investigated.Results: 718 patients provided data for analysis, of which 642 (89%) had some difficulty with at least one driving task and 72 (10%) had some difficulty with all nine tasks. Three domains of driving difficulty were identified: dynamic driving scenarios, crossing traffic, and the physical act of driving. Chronic widespread pain, knee and back pain, fatigue, high disease activity and anxiety/depression were significantly associated with reporting driving difficulties across all three domains, particularly the physical act of driving. After adjusting for socio‐demographic, disease activity, physical and mental health, driving difficulties in each domain were associated with a 2‐3 times increased likelihood of restricted work productivity and with an increased risk of sickness absence in the past seven days.Conclusion: driving difficulties are common in individuals with axSpA and impact on work, even after adjusting for clinical status. Improving understanding and awareness of driving disability will help direct advice and resources to enable individuals to remain independent and economically active.

Background/Aims Much discussion surrounds the optimal therapeutic treatment plan for biologic and targeted synthetic disease modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) when treating psoriatic arthritis (PsA). The current study aims to identify predictors of treatment response among PsA patients initiating bDMARD/tsDMARD treatment, focusing on disease activity, functional status (Health Assessment Questionnaire, HAQ), and comorbidities. Methods The systematic review of clinical trials and observational studies used Medline, Embase and Cochrane databases. Eligible studies included full text papers with quantitative estimates of effect (or data to allow these to be computed). Papers also required a validated assessment of treatment response i.e., Minimal Disease Activity (MDA), or some other marker of treatment response such as treatment continuation. Case reports and conference abstracts were excluded. Results From 2824 articles identified, 27 were included. Across these, >15 different outcomes were used, and measured at > 10 different timepoints. There was consistent evidence to suggest that higher baseline disease activity was associated with a reduction in the likelihood of treatment response, see Table 1. Some studies reported up to 20% reduction in odds of LDA at 6 months associated with each 1 unit increase in DAPSA. Others demonstrated that patients with a high DAS28 (>3.2) experienced over a 90% reduction in the odds of MDA at 12 weeks. Eleven studies (from 15) demonstrated a significant association between baseline function and odds of treatment response. Each 1 unit increase in HAQ-DI decreased the odds of a good EULAR response at 3 months by up to 66%. The presence of comorbidities was also consistently associated with a decrease in treatment response. Studies showed that the presence of comorbidities at baseline lessened the odds of MDA at 6 months by up to 80%. Others reported that comorbidities were associated with a reduction in the odds of 5 year treatment persistence by up to 40%. Conclusion This review shows clear evidence of reduced bDMARD/tsDMARD response in PsA among patients with disease activity, poor function, and comorbidities. Clinicians should be aware of the reduced chances of treatment success and should consider early review of therapy, to consider whether treatment escalation or switching is required. Disclosure C. Addae-Kyereme: None. S. Lembke: None. G.J. Macfarlane: None. G.T. Jones: None.

Background/Aims MRI evidence of active sacroiliitis (sacroiliac joint bone marrow oedema (BMO)) is commonly used to assist diagnosis and classification of axial spondyloarthritis (axSpA). Non-steroidal anti-inflammatory drugs (NSAIDs) are used as first-line therapy, and for persistent clinical symptoms continuous treatment is recommended. Prescribed in primary care, and widely available over-the-counter, many patients are already taking NSAIDs when first presenting to rheumatology. We hypothesised that among patients with axSpA, NSAID use would lead to an underestimation of sacroiliac joint BMO. Methods Adults with axSpA were recruited from NHS rheumatology clinics and asked to discontinue their NSAIDs for 1-2wks before undergoing a sacroiliac joint MRI (Scan 1) using a standardised protocol. All participants then re-started their NSAIDs. Those who scanned positive for BMO lesions, as determined using internationally recognised (ASAS) definitions, underwent a second scan 6wks after restarting NSAIDs. Scans were read independently by 2 readers (adjudicated by a 3rd, if required), blinded to participants’ clinical characteristics and timepoint. We determined the proportion of participants who scanned negative at Scan 2 (on NSAIDs) who had previously scanned positive at Scan 1 (off NSAIDs). Results 311 participants were recruited from 34 centres. Table 1 shows participants’ baseline characteristics. Almost all participants (296; 95%) completed the NSAID washout and underwent Scan 1. However, 135 (50%) reported an increase in spinal pain (median increase: 2 points on a 0-10 numerical rating scale; inter-quartile range: 1-3), and 166 (61%) reported worsening of disease activity (median increase in BASDAI: 0.9; 0.5-1.6). At Scan 1, 149 (50%) were positive for BMO lesions. 131 (88%) participants underwent the six-week follow-up scan, of whom 31 scanned negative (24%; 95%CI: 17-32%). Conclusion These findings suggest that NSAIDs influence sacroiliac BMO and, where sacroiliitis is present, around one-in-four show resolution of lesions when NSAIDs are present - with important implications for axSpA diagnosis and classification. If patients with axSpA (or suspected axSpA) are willing to attempt NSAID washout prior to MRI, this should be considered. There may be concerns about increases in disease activity or spinal pain, but we also provide evidence that almost all patients who attempt washout can successfully achieve it. Disclosure G.T. Jones: None. A.N. Bennett: Consultancies; Abbvie, Eli Lilly, MSD, Novartis, Pfizer, UCB. Honoraria; AbbVie, Biogen, Novartis, Pfizer, UCB. Grants/research support; Pfizer. R. Sengupta: Consultancies; AbbVie, Biogen, Eli Lilly, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Biogen, Celgene, Eli Lilly, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Celgene, Novartis, UCB. P.M. Machado: Honoraria; AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche, UCB. H. Marzo-Ortega: Consultancies; Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Biogen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCB. Grants/research support; Janssen, Novartis, UCB. L. Aucott: None. G.J. Macfarlane: None.

Background/Aims In axial spondyloarthritis, it has been shown that while some adverse lifestyle factors (smoking and high body mass index (BMI)) are less likely to respond to TNF inhibition (TNFi), those who drink alcohol are more likely to respond to treatment - a result currently unexplained, and unlikely to be causal. We aimed to investigate these associations in psoriatic arthritis (PsA) and to quantify the impact of lifestyle factors on TNFi treatment response. Methods Adults with PsA commencing TNFi were identified via the European Spondyloarthritis Research Collaboration Network (https://eurospa.eu). Participants were required to have data on lifestyle factors (smoking, alcohol consumption, and/or BMI) recorded within ±30 days of commencing TNFi. The relationship between lifestyle factors and treatment outcome (ACR-50 response criteria at 12 months) was assessed using logistic regression, adjusted for age, sex, country, year of TNFi initiation, disease duration and baseline disease activity (DAS28). The analysis was then repeated for other treatment response criteria: ACR-20, ACR-70, DAPSA28-remission, DAPSA68-remission and Minimal Disease Activity. Results From 12 PsA registries, 9409 participants were included, 21% of whom were current smokers, 54% drank alcohol, 38% were overweight and 29% were obese. Other baseline characteristics are shown in Table 1. Among smokers, 18% met ACR-50 response criteria at 12 months, versus 26% of non-smokers, an association that remained after adjusting for potential confounders (adjusted odds ratio: 0.59; 95%CI: 0.48-0.72). Participants who were overweight (adjusted odds ratio: 0.80; 0.64-0.99) or obese (0.57; 0.44-0.72) were also less likely to achieve treatment response, compared to patients of normal weight. Similar results were seen across other outcome measures. The proportion who achieved ACR-50 response did not differ between patients who did/did not consume alcohol (both 22%). Conclusion Smoking and high BMI were associated with substantial decreases in the likelihood of TNFi response. The addition of non-pharmacological therapy, including the modification of adverse lifestyle factors, may offer the potential to enhance treatment outcomes. For example, if 100 patients were able to give up smoking when commencing TNFi, an additional eight would achieve ACR-50 at 12 months. Previous findings regarding alcohol and treatment response in axSpA were not replicated in PsA. Disclosure G.T. Jones: None. O. Rotariu: None. B. Michelsen: None. B. Glintborg: None. B. Gudbjornsson: None. T.J. Love: None. D. Nordström: None. T. Sokka: None. J. Vencovský: None. P. Horák: None. Z. Rotar: None. M. Tomšič: None. M. van der Sande: None. M.J. Nissen: None. B. Möller: None. C. Codreanu: None. J.K. Wallman: None. K.M. Fagerli: None. S.H. Rasmussen: None. L.M. Ørnbjerg: None. M.J. Santos: None. P. Carvalho: None. M.L. Hetland: None. M. Østergaard: None. G.J. Macfarlane: None.

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.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.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) (β = 0.64 [IQR 0.26, 1.02]), but was not related to meeting ASDAS response criteria.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.

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 5,254 controls from 5 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.

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.

Introduction:Previous epidemiological studiesofneuropathicpainhave reported a rangeofprevalences andfactorsassociatedwiththedisorder. Objectives:This study aimed to verify these characteristicsina largeUKcohort. Methods:A cross-sectionalanalysiswas conductedof148,828UKBiobankparticipants who completed a detailed questionnaire on chronicpain.TheDouleur Neuropathique en Quatre Questions(DN4) was used to distinguish betweenneuropathicpain(NeuP) and non-neuropathicpain(non-NeuP)inparticipants withpainofat least 3 months' duration. Participants were also identified with less than 3 months'painor withoutpain(NoCP). Multivariable regression was used to identifyfactorsassociatedwith NeuP compared with non-NeuP and NoCP, respectively. Results:Chronicpainwas presentin76,095 participants (51.1%).TheoverallprevalenceofNeuP was 9.2%.Neuropathicpainwas significantlyassociatedwith worse health-related qualityoflife, having a manual or personal service type occupation, and younger age compared with NoCP. As expected, NeuP wasassociatedwith diabetes and neuropathy, but also other pains (pelvic, postsurgical, and migraine) and musculoskeletal disorders (rheumatoid arthritis, osteoarthritis, and fibromyalgia).Inaddition, NeuP wasassociatedwithpaininthelimbs and greaterpainintensity and higher body mass index compared with non-NeuP. Female sex wasassociatedwith NeuP when compared with NoCP, whereas male sex wasassociatedwith NeuP when compared with non-NeuP. Conclusion:This isthelargest epidemiological studyofneuropathicpainto date.Theresults confirm thatthedisorder is commonina populationofmiddle- to older-aged people with mixed aetiologies and isassociatedwith a higher health impact than non-neuropathicpain.

To investigate the distribution of patient-reported outcomes (PROs) in axial spondyloarthritis (axSpA) patients 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 New York criteria for ankylosing spondylitis (AS) versus non-radiographic axSpA (nr-axSpA) patients.Fifteen European registries contributed PRO scores for pain, fatigue, patient global, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire (HAQ) from 19,498 axSpA patients. Changes in PROs and PRO "remission" rates (definitions: ≤20 mm for pain, fatigue, patient global, BASDAI and BASFI; ≤0.5 for HAQ) were calculated at 6, 12 and 24 months of treatment.Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, six months after start of a 1st 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), patient global (66/29/21/20), BASDAI (58/26/21/19), BASFI (46/20/16/16) and HAQ (0.8/0.4/0.2/0.2). Patients with AS, n=3281 had a slightly better response than nr-axSpA patients, n=993. LUNDEX-adjusted "remission" rates at 6 months for pain/fatigue/patient global/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the non-radiographic axSpA cohort. Better PRO responses were seen with a 1st TNFi compared to 2nd and 3rd TNFi.AxSpA patients starting a TNFi achieved high PRO "remission" rates, most pronounced in those fulfilling the modified New York criteria and for the first TNFi.

Funding Information: The Republic of Turkey Ministry of National Education for the PhD studentship. Publisher Copyright: © 2022 The Author(s) Objectives: To develop evidence-based expert recommendations for non-pharmacological treatments for pain, fatigue, sleep problems, and depression in fibromyalgia. Methods: An international, multidisciplinary Delphi exercise was conducted. Authors of EULAR and the Canadian Fibromyalgia Guidelines Group, members of the American Pain Society and clinicians with expertise in fibromyalgia were invited. Participants were asked to select non-pharmacological interventions that could be offered for specific fibromyalgia symptoms and to classify them as either core or adjunctive treatments. An evidence summary was provided to aid the decision making. Items receiving >70% votes were accepted, those receiving

Aims Although total knee arthroplasty (TKA) is a highly successful procedure, about 20% of patients remain dissatisfied postoperatively. This proportion is derived from dichotomous models of the assessment of surgical success or failure, which may not reflect the spectrum of outcomes. The aim of this study was to explore differing responses to surgery, and assess whether there are distinct groups of patients with differing patterns of outcome. Methods This was a secondary analysis of a UK multicentre TKA longitudinal cohort study. We used a group-based trajectory modelling analysis of Oxford Knee Score (OKS) in the first year following surgery with longitudinal data involving five different timepoints and multiple predictor variables. Associations between the derived trajectory groups and categorical baseline variables were assessed, and predictors of trajectory group membership were identified using Poisson regression and multinomial logistic regression, as appropriate. The final model was adjusted for sociodemographic factors (age, sex) and baseline OKS. Results Data from 731 patients were available for analysis. Three distinct trajectories of outcome were identified: “poor” 14.0%, “modest” 39.1%, and “good” 46.9%. The predicted probability of membership for patients assigned to each trajectory group was high (0.89 to 0.93). Preoperative mental, physical health, and psychosocial factors determined which trajectory is likely to be followed. Poor responders were characterized by a comparatively small number of factors, preoperative expectations of pain and limitations, coping strategies, and a lower baseline physical health status, while the good responders were characterized by a combination of clinical, psychosocial, mental health, and quality of life factors. Conclusion We identified three distinct response trajectories in patients undergoing TKA. Controlling for baseline score, age, and sex, psychosocial factors such as expectations of pain and limited function and poor coping strategies differentiated the trajectory groups, suggesting a role for preoperative psychosocial support in optimizing the clinical outcome. Cite this article: Bone Joint J 2021;103-B(6):1096–1102.

Objective: To compare the impact of symptoms and health care utilization of people diagnosed with fibromyalgia, people who fulfill the criteria but are not diagnosed, and people with chronic pain. Methods: We recruited people who had participated in a previous population survey across Scotland and who reported some typical fibromyalgia symptoms or had received a diagnosis of fibromyalgia. Responses to a postal questionnaire were used to define mutually exclusive groups: people who had a fibromyalgia diagnosis, who met criteria for fibromyalgia, and who had chronic pain. Results: Participants included 85 people with a diagnosis of fibromyalgia, 110 who met criteria for fibromyalgia, and 133 with chronic pain. The mean age across groups ranged 57–59 years, but the percentage female varied markedly: 86%, 64%, and 67%, respectively. Compared to those with chronic pain, participants with a fibromyalgia diagnosis were more likely to be out of employment due to health. An average of 3 years was needed to receive a fibromyalgia diagnosis, and more than half were diagnosed in secondary care (most commonly rheumatology). The fibromyalgia diagnosis and criteria groups were similar in terms of symptom impact, quality of life, and life satisfaction but were worse than the chronic pain group. Participants who had received a diagnosis of fibromyalgia reported the poorest health care experiences. Conclusion: An urgent need exists for a model of care for fibromyalgia to ensure prompt diagnosis, access to evidence‐based care, and long‐term support, with the aim of improving function. The data suggest that diagnosis in men may be overlooked, and this finding warrants further study.

Previous epidemiological studies of neuropathic pain have reported a range of prevalences and factors associated with the disorder. This study aimed to verify these characteristics in a large UK cohort. A cross sectional analysis was conducted of 148,828 UK Biobank participants who completed a detailed questionnaire on chronic pain. The Douleur Neuropathique en Quatre Questions (DN4) was used to distinguish between neuropathic pain (NeuP) and non-neuropathic pain (Non-NeuP) in participants with pain of at least 3 months’ duration. Participants were also identified with less than 3 months’ pain or without pain (NoCP). Binomial and multinomial regression were used to identify factors associated with NeuP compared to Non-NeuP and NoCP respectively. Chronic pain was present in 76,095 participants (51.1%). The overall prevalence of NeuP was 9.2% (13,744/148,828). NeuP was significantly associated with worse health-related quality of life, having a manual or personal service type occupation and younger age compared to NoCP. As expected NeuP was associated with diabetes and neuropathy, but also other pains (pelvic, post-surgical and migraine) and musculoskeletal disorders (rheumatoid arthritis, osteoarthritis and fibromyalgia). Additionally, NeuP was associated with pain in the limbs and greater pain intensity and higher BMI compared to Non-NeuP. Female gender was associated with NeuP when compared to NoCP, whilst male gender was associated with NeuP when compared to Non-NeuP. This is the largest epidemiological study of neuropathic pain to date. The results confirm that the disorder is common in the general population and is associated with a higher health impact than non-neuropathic pain.

ObjectiveTo 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).MethodsFollowing 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.ResultsFour 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 ConclusionThese recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases.

ObjectiveCognitive–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.MethodsA 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.Results996 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.ConclusionsA 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 numberClinicalTrials.gov Registry (NCT02668003).

Contains fulltext : 238651.pdf (Publisher’s version ) (Open Access) BACKGROUND: Individuals' perceptions of back pain may shape what they do in response to manage their pain, for example, self-care, medication and seeking healthcare. Illness perceptions encompass a variety of beliefs such as how long pain is expected to last and whether treatments are perceived to control pain. Whether these beliefs meaningfully cluster and whether these clusters are associated with how people manage their back pain are currently unknown. METHODS: 1,343 individuals with back pain from a general population sample completed the brief Illness Perceptions Questionnaire and measures about their pain and illness behaviours. Using a two-stage cluster analysis, we identified four distinct clusters of individuals. Logistic regression was used to investigate relationships between cluster membership and illness behaviours. RESULTS: After adjustment for socio-demographic characteristics, pain severity, interference and duration, relative to a low threat illness perception cluster, a high threat cluster was more likely to have contacted a general practitioner (OR: 3.03, 95% CI: 1.75, 5.23) and a moderate threat-high treatment control cluster was more likely to have consulted a physical therapist (OR: 2.21, 95% CI: 1.26, 3.87). Both the moderate threat-high treatment control cluster and high threat cluster were also less likely to have reported self-care (OR: 0.64, 95% CI: 0.43, 0.95; OR: 0.53, 95% CI: 0.34, 0.83, respectively). CONCLUSIONS: The cluster analysis provided a meaningful classification of individuals based on their cognitive illness perceptions of their back pain, as these clusters were associated with different illness behaviours. Interventions which modify clusters of illness perceptions may be effective in influencing how individuals respond to back pain. SIGNIFICANCE: Within a general population setting, we identified four clearly distinct groups of people based on the perceptions they held about their back pain. These groupings seemed to reflect meaningful characterisations as they differed based on the characteristics of their pain (e.g., severity and duration) and, after adjustment for these characteristics, were associated with different ways of managing pain. Interventions which focus on targeting the sets of illness perceptions that people hold may be effective in influencing how individuals manage back pain.

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 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 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.

Background/Aims Pharmacological management of axial spondylarthritis (axSpA) seeks to control inflammation. Even if successful, available evidence suggests that many patients continue to experience pain. The aim of the current study was to determine the prevalence and characteristics of severe pain among persons with axSpA. Methods The Scotland Registry for Ankylosing Spondylitis (SIRAS) collected clinical and patient-reported data from adults seen in secondary care in Scotland with a clinical diagnosis of ankylosing spondylitis. Questionnaires asked about severe pain (high pain intensity; high pain interference; and extreme/unbearable pain), lifestyle, and various aspects of health. The relationship between severe pain and clinical/patient-reported factors was assessed using logistic regression. Results 929 participants had pain data available (73% male; median symptom duration 20yrs). High pain intensity and pain interference were more common (57% and 42%) than extreme/unbearable pain (11%). Prevalence did not differ with age, although women were less likely to report severe pain than men (Odds Ratios (ORs) 0.56-0.61) as were those with longer duration of education, and those from more affluent areas. The odds of severe pain increased with every 1 unit increase in BASFI (ORs 1.44-1.56). Strong associations were also seen with disease activity, spinal mobility, fatigue, poor sleep, and worse quality of life. Conclusion In axSpA, severe pain is common, with a clear socio-economic gradient and major impact on quality of life. Rheumatologists need to be aware of the large unmet need in terms of pain management in this patient group with around 1 in 9 patients reporting extreme/unbearable pain. Disclosure G.T. Jones: Grants/research support; Research grant income for biologics registers in axSpA and PsA from the British Society for Rheumatology. The Society receives income from AbbVie, Pfizer, UCB and Amgen to support these registers, current analysis funded by GlaxoSmithKline who were provided with a copy of the results prior to submission. O. Rotariu: None. L.E. Dean: None. A.G. MacDonald: None. G.J. Macfarlane: Grants/research support; Research grant income for biologics registers in axSpA and PsA from the British Society for Rheumatology. The Society receives income from AbbVie, Pfizer, UCB and Amgen to support these registers, current analysis was funded by GlaxoSmithKline who were provided with a copy of the manuscript prior to submission.

Background/Aims Inflammatory bowel disease (IBD) is one of the extra-musculoskeletal manifestations associated with axial spondyloarthritis (axSpA). A previous meta-analysis reported a pooled prevalence of 6.8% (95% CI 6.1% to 7.7%). Amongst those commencing anti-TNFα therapy in BSRBR-AS it has been reported that patients with IBD were much less likely to have been prescribed etanercept (a soluble fusion protein) in comparison to the monoclonal antibodies in this cohort (adalimumab, certolizumab pegol and golimumab). A large study from Denmark of approximately 80,000 patients with an autoimmune disease (other than IBD) for which anti-TNFα therapy is an indication found a significant excess risk of IBD in those treated with etanercept, an excess which was not observed with other anti-TNFα agents. We therefore aimed to determine, amongst patients in BSRBR-AS, whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic and other therapies, and whether specifically the risk is higher in patients treated with etanercept. 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) between biologic treatment and other treatment groups. We thereafter conducted a systematic review (involving observational studies and randomised controlled trials) to perform a meta-analysis to quantify the difference in incidence of IBD between treatment groups. Results In BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to non-exposed patients (IRD 12.4 95% CI [5.5-19.4]). In meta-analysis, this finding was replicated across observational studies but not seen in placebo controlled RCTs IRD 2.2 95% CI (-4.1-8.5). Data from BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to etanercept compared to other anti-TNFα therapies (IRD -1.9 per 1000 py 95% CI [-15.2-11.5]). Trials and their extensions suggest a small (and not statistically significant) absolute increased incidence associated with etanercept of between 2.1 and 5.6 per 1000py compared to other anti-TNFα therapies. Conclusion An excess risk of IBD amongst persons treated with biologics is likely not causal but evidence from trials suggest that etanercept is associated with an increased risk compared to other anti-TNFα therapies, albeit with considerable uncertainty. Disclosure G.J. Macfarlane: Grants/research support; GJM is Chief Investigator a grant from BSR to fund the AS register. BSR received funds from Pfizer, AbbVie and UCB to support this work. R. Biallas: None. L.E. Dean: None. G.T. Jones: Grants/research support; GTJ is Co-Investigator on a grant from BSR to fund the AS register. BSR received funds from Pfizer, AbbVie and UCB to support this work. N. Goodson: Other; NG is Chair of the BSR Registers Committee. O. Rotariu: None.

Background/Aims Pain in the distal arm (elbow/forearm/wrist/hand) is common amongst working-aged adults and causes substantial work disability. The best strategy for managing arm pain is uncertain and patients are often referred to physiotherapy. We have recently shown in a randomised controlled trial (the ARM trial) that long-term disability was reduced among patients advised to remain active while awaiting physiotherapy, compared to advice to rest. The aim of the current study was to determine whether this approach is effective among workers, who may have to continue activities that are causing or exacerbating their pain; and whether there was any differential effect between workers doing manual versus non-manual work, and exposed versus not exposed to a range of physically demanding activities involving the upper limb. Methods The ARM trial (ISRCTN79085082) recruited patients with distal arm pain from 14 outpatient physiotherapy departments across the UK. Eligible consenting patients were randomised equally to: Advice to remain active, while awaiting physiotherapy; Advice to rest, while awaiting physiotherapy; or Immediate physiotherapy. This was done using a mixed randomisation/minimisation algorithm, maintaining treatment balance regarding treatment centre, gender, laterality, a broad categorisation of diagnosis, and baseline arm function. The primary outcome was freedom from disability at 26wks, as determined using the modified DASH (Disabilities of the Arm, Shoulder and Hand) questionnaire. In the current study, an intention-to-treat analysis was undertaken for the sub-group of trial participants in paid employment > =20hrs/wk at the start of the study. Results are presented as odds ratios, with 95% confidence intervals, for the probability of recovery. Results We have previously shown, among persons awaiting physiotherapy for distal arm pain, that advice to remain active is associated with improved long-term outcomes. Although not powered as a trial for workers, our findings suggest that these results also hold true for people in paid work - and there is certainly no evidence that this advice is detrimental. We have also shown that fast-track physiotherapy seems to confer no benefit, over and above therapy delivered after a period on a waiting list which calls into question the benefit of rapid access rehabilitation programmes. Conclusion We have previously shown, among persons awaiting physiotherapy for distal arm pain, that advice to remain active is associated with improved long-term outcomes. Although not powered as a trial for workers, our findings suggest that these results also hold true for people in paid work who may have to continue activities that are causing or exacerbating their pain. Certainly, there is no evidence that this advice is detrimental. We have also shown that fast-track physiotherapy seems to confer no benefit, over and above therapy delivered after a period on a waiting list which calls into question the benefit of rapid access rehabilitation programmes. Disclosure G.T. Jones: None. G.J. Macfarlane: None. K. Burton: Royalties; Was involved in the development of The Arm Book (ISBN: 978-0117069145) to which the experimental leaflet in this trial is related, and may receive future royalties on the booklet. K. Walker-Bone: None.

ObjectivesTo 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.DesignQualitative interviews embedded within an observational questionnaire study of individuals with musculoskeletal (MSK) conditions.SettingUK primary care (general practices), and secondary care-based rheumatology services.ParticipantsIndividuals 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 measuresThe 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.Results491 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.ConclusionLockdown 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.

Fibromyalgia is a common and complex long-term pain condition. Despite advancements in our understanding and treatment of fibromyalgia, patients report patchy health care provision and frustrating journeys through the health care system. To inform how best to deliver care, we undertook 2 narrative reviews examining existing evidence on (1) models of care for fibromyalgia and (2) patients' experiences, preferences, and unmet needs regarding their health care. Seven databases were systematically searched. Quantitative data was narratively synthesised and qualitative data thematically analysed. No evidence-based model of care covering the patient journey through the entire health care system was identified. Limited evidence suggests no clear benefit for ongoing care in secondary care settings. Patients with fibromyalgia report difficult interactions with the health care system that might equally be expressed by those with other long-term conditions, such as inconsistent and poorly coordinated care. However, they also face unique problems; fibromyalgia was often not viewed as a real condition, resulting in difficult encounters with health care staff, in particular not feeling believed or listened to. Significant delays in diagnosis were commonplace. Positive care experiences such as being listened to and shared decision-making made patients feeling better informed, well supported, and more satisfied. There is little evidence to inform how best to organise health care for patients with fibromyalgia and ensure care is delivered in a coordinated and consistent way. These findings provide a strong rationale for developing a new model of care for fibromyalgia.

Objectives: Fatigue is a challenging feature of all inflammatory rheumatic diseases. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomised Trial) included remotely delivered personalised exercise programme (PEP) or cognitive-behavioural approach (CBA) interventions. The aim of this nested qualitative evaluation was to understand rheumatology health professionals (therapists’) perspectives of delivering the interventions in the LIFT trial. Methods: A subgroup of therapists who had delivered the personalized exercise programme (PEP) and cognitive-behavioural approach (CBA) interventions took part in semi-structured telephone interviews.Results: Seventeen therapists (13 women and 4 men) who delivered PEP (n = 8) or CBA (n = 9) interventions participated. Five themes were identified. In ‘The benefits of informative, structured training’, therapists described how they were able to practice their skills, and the convenience of having the LIFT manual for reference. When ‘Getting into the swing of it’, supporting patients gave therapists the confidence to tailor the content of the manual to each patient. Clinical supervision supported therapists to gain feedback and request assistance when required. In ‘Delivering the intervention’, therapists reported that patients valued the opportunity to talk about their fatigue and challenge their beliefs. In ‘Challenges in delivering the LIFT intervention’, therapists struggled to work in partnership with patients who lacked motivation or stopped engaging. Finally, in ‘LIFT developing clinical skills’, therapists gained confidence and professional satisfaction, seeing patients’ fatigue improve over time.Conclusion: The findings support the provision of training for rheumatology health professionals to remotely deliver fatigue-management interventions. Insights from these trials can be used to better improve clinical practice and service provision.Lay summary What does this mean for patients ? Fatigue can be a challenge in inflammatory rheumatic diseases (IRDs). The LIFT study (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomized Trial) explored interventions to support people with fatigue. These were: a cognitive-behavioural approach (CBA), a personalized exercise programme (PEP), or usual care. People with IRDs were chosen randomly to take part in seven sessions of CBA, seven sessions of PEP or usual care. All sessions (aside from the first PEP session) were delivered over the phone. The aim of this study was to explore therapists' experiences of delivering the intervention. Seventeen therapists (13 women and 4 men) took part; eight had delivered the PEP intervention, and 9 delivered the CBA intervention. Therapists who delivered LIFT told us they enjoyed the chance to practice their skills, and that the LIFT manual gave them the confidence to tailor the intervention to each patient. Clinical supervision was valued. Therapists also shared that LIFT improved their skills and they were happy to see patients' fatigue improve over time. These new results can inform clinical practice, and how services are provided.

ObjectivesPharmacological management of axial spondylarthritis (axSpA) seek to control inflammation. Even if successful, available evidence suggests that many patients continue to experience pain. The aim of the current study was to determine the prevalence and characteristics of severe pain, among persons with axSpA.MethodsThe Scotland Registry for Ankylosing Spondylitis (SIRAS) collected clinical and patient-reported data from adults seen in secondary care in Scotland with a clinical diagnosis of ankylosing spondylitis. Questionnaires asked about severe pain (high pain intensity; high pain interference; and extreme/unbearable pain), lifestyle, and various aspects of health. The relationship between severe pain and clinical/patient-reported factors was assessed using logistic regression.Results929 participants had pain data available (73% male; median symptom duration 20yrs). High pain intensity and pain interference were more common (57% and 42%) than extreme/unbearable pain (11%). Prevalence did not differ with age, although women were less likely to report severe pain than men (Odds Ratios (ORs) 0.56-0.61) as were those with longer duration of education, and those from more affluent areas. The odds of severe pain increased with every 1 unit increase in BASFI (ORs 1.44-1.56). Strong associations were also seen with disease activity, spinal mobility, fatigue, poor sleep, and worse quality of life.ConclusionIn axSpA, severe pain is common, with a clear socio-economic gradient and major impact on quality of life. Rheumatologists need to be aware of the large unmet need in terms of pain management in this patient group with around 1 in 9 patients reporting extreme/unbearable pain.KEY MESSAGESWhat is already known about this subject?Axial spondyloarthritis is a painful inflammatory arthritis, although the epidemiology of specific pain phenotypes – and ‘severe’ pain in particular – is unknown.What does this study add?Severe pain (extreme/unbearable pain, pain of high intensity, or with a high level of interference) is commonly reported among people with axial spondyloarthritis.Three-quarters of individuals reporting severe pain still report severe pain two years later.Patients with severe pain are characterised by certain demographic characteristics, higher disease activity, poorer function, and a number of other clinical and lifestyle factors.How might this impact on clinical practice or future developments?Rheumatologists should be aware of the large unmet need in terms of pain management in this patient group. Specific pain management strategies should be considered to complement therapies aimed at reducing inflammation.

BackgroundThe 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.AimTo profile UK healthcare services for people with fibromyalgia: provision of National Health Services (NHS) and use of non-NHS services by people with fibromyalgia.MethodsTwo 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.ResultsSurvey 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.ConclusionThis 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.

Objectives Fatigue can be a disabling symptom of inflammatory rheumatic diseases (IRD). LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomised Trial) is a randomised trial of remotely delivered cognitive-behavioural approach (CBA) or personalised exercise programme (PEP) interventions, compared with usual care. The aim of this nested qualitative study was to evaluate participants’ experiences of taking part in the intervention, including their ideas about future service delivery. Methods Semi-structured telephone interviews with a subgroup of LIFT participants to discuss their views and experiences of the interventions. Results Forty-three participants (30 women) from six sites who had participated in CBA (n = 22) or PEP (n = 21) interventions took part. Five themes were identified in the thematic analysis: In ‘Not a miracle cure, but a way to better manage fatigue’, LIFT could not cure fatigue, however, most felt better able to manage after participating. Participants valued ‘Building a therapeutic relationship’ with the same therapist throughout the intervention. In ‘Structure, self-monitoring and being accountable’, participants liked the inclusion of goal setting techniques, and were motivated by reporting back to the therapist. After taking part in the interventions, participants felt ‘Better equipped to cope with fatigue’; more confident and empowered. Lastly, participants shared ideas for ‘A tailored programme delivered remotely’, including follow-up sessions; video calling; and group-based sessions for social support. ConclusionMany participants engaged with the LIFT interventions and reported benefits of taking part. This suggests an important future role for the remote delivery of fatigue self-management. Lay summary What does this research mean for patients? Fatigue can be a disabling symptom in inflammatory rheumatic diseases (IRDs). The LIFT Study (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomised Trial) looked at different interventions; a cognitive-behavioural approach (CBA), Personalised Exercise Programme (PEP), or usual care. CBA sessions addressed unhelpful thoughts and feelings. The PEP sessions supported people with IRDs to gradually increase their exercise levels. People with IRDs were randomly selected to take part in seven sessions of CBA, seven sessions of PEP, or usual care. All sessions except the first PEP session were delivered remotely by phone. The aim of this study was to explore people’s experiences of taking part. Forty-three people with IRDs (30 women, 13 men) were interviewed from six UK locations. Twenty-two took part in the CBA sessions, and twenty-one took part in PEP. People with IRDs who took part in LIFT told us about a range of benefits. These included feeling less fatigue and more confidence. Those in PEP told us they felt stronger. People with IRDs shared that they liked being able to talk about their fatigue with a supportive therapist. These are encouraging results for remotely-delivered research to support people with fatigue.

ObjectiveTo 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).MethodsFifteen 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.ResultsHeterogeneity 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.ConclusionPatients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

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.

Summary Objective To determine whether good versus poor outcome trajectories and predictors of poor outcome obtained in a derivation study could be replicated in an independent sample of persons undergoing knee arthroplasty (KA). Methods We used data from TRIO-POPULAR, a prospective cohort study of 926 participants who underwent KA in the United Kingdom. The participants were assessed preoperatively and 6-weeks, 6- and 12-months postoperatively. The Oxford Knee Score was the primary outcome and a variety of pre-operative predictors of outcome were selected. The outcome measure and the predictors were selected to most closely align with a previously published derivation study of good versus poor outcome. Confirmatory two-piece latent class growth curve analyses were used to model outcome and regression was used to identify predictors of outcome class. Results Trajectories for the Oxford Knee Scores from TRIO-POPULAR replicated trajectories for WOMAC Pain and Function scores from the previously published derivation study. Multivariable predictors of poor outcome were pain catastrophizing (odds ratio = 1.125, 95% CI = 1.048, .206, p = 0.001) and comorbidity (odds ratio = 1.134, 95%CI = 1.049, 1.227, p = 0.002. Pain catastrophizing also predicted poor outcome in the derivation study. Conclusions Good and poor outcome trajectories replicated those found in the previously published derivation study. Our model-based method produces stable outcome trajectories despite using data from different countries and participants with substantively different characteristics. Predictors of poor outcome were somewhat inconsistent between the cross-validation and derivation studies. Pain catastrophizing was the only consistent poor outcome predictor.

L.K. is a fellow in the Canadian Institutes of Health Research (CIHR) Strategic Training in Advanced Genetic Epidemiology (STAGE) programme and is supported by the CIHR Doctoral Research Award from the Frederick Banting and Charles Best Canada Graduate Scholarships (GSD-137441). Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by the National Institutes of Health (U19-CA148127, CA148127S1). Genotyping for the TRICL-ILCCO OncoArray was supported by in-kind genotyping at Centre for Inherited Disease Research (CIDR) (26820120008i-0–6800068-1). Genotyping for the Head and Neck Cancer OncoArray performed at CIDR was funded by the US National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780–0. CAPUA study was supported by FIS-FEDER/Spain grant numbers FIS-01/310, FIS-PI03–0365 and FIS-07-BI060604, FICYT/Asturias grant numbers FICYT PB02–67 and FICYT IB09–133, and the University Institute of Oncology (IUOPA), of the University of Oviedo and the Ciber de Epidemiologia y Salud Publica. CIBERESP, SPAIN. The work performed in the CARET study was supported by the National Institute of Health (NIH)/National Cancer Institute (NCI): UM1 CA167462 (PI: Goodman), National Institute of Health UO1-CA6367307 (PIs Omen, Goodman); National Institute of Health R01 CA111703 (PI Chen), National Institute of Health 5R01 CA151989 (PI Doherty). The Liverpool Lung Project is supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH (National Cancer Institute) grants CA092824, CA090578 and CA074386. The Multiethnic Cohort Study was partially supported by NIH Grants CA164973, CA033619, CA63464 and CA148127. The work performed in MSH-PMH study was supported by the Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. The Norway study was supported by Norwegian Cancer Society, Norwegian Research Council. The work in TLC study has been supported in part the James & Esther King Biomedical Research Program (09KN-15), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant (P50 CA119997) and by a Cancer Center Support Grant (CCSG) at the H. Lee Moffitt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center (grant number P30-CA76292). The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center’s BioVU, which is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH. Dr Melinda Aldrich is supported by the by NIH/National Cancer Institute 5K07CA172294. The Copenhagen General Population Study (CGPS) was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The NELCS study: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Kentucky Lung Cancer Research Initiative (KLCRI) was supported by the Department of Defense (Congressionally Directed Medical Research Program, U.S. Army Medical Research and Materiel Command Program) under award number: 10153006 (W81XWH-11–1-0781). Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. This research was also supported by unrestricted infrastructure funds from the UK Center for Clinical and Translational Science, NIH grant UL1TR000117 and Markey Cancer Center NCI Cancer Center Support Grant (P30 CA177558) Shared Resource Facilities: Cancer Research Informatics, Biospecimen and Tissue Procurement, and Biostatistics and Bioinformatics. The research undertaken by M.D.T., L.V.W. and M.S.A. was partly funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.D.T. holds a Medical Research Council Senior Clinical Fellowship (G0902313). The Tampa study was funded by Public Health Service grants P01-CA68384 and R01-DE13158 from the National Institutes of Health. The University of Pittsburgh head and neck cancer case–control study is supported by US National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; grants 04/12054–9 and 10/51168–0). The authors thank all the members of the GENCAPO team. This publication presents data from the Head and Neck 5000 study. The study was a component of independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707–10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Human papillomavirus (HPV) serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commission’s fifth framework programme (QLK1– 2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte and Padova University (CPDA057222). The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) awards IG 2011 10491 and IG 2013 14220 to S.B. and by Fondazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97–0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (01/01768–2). The IARC Central Europe study was supported by the European Commission’s INCO-COPERNICUS Program (IC15-CT98–0332), US NIH/National Cancer Institute grant CA92039 and World Cancer Research Foundation grant WCRF 99A28. The IARC Oral Cancer Multicenter study was funded by grant S06 96 202489 05F02 from Europe against Cancer; grants FIS 97/0024, FIS 97/0662 and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is financially supported by the European Commission (DG SANCO) and the International Agency for Research on Cancer.

Fibromyalgia (FM) is a common chronic pain disorder that presents diagnostic challenges for clinicians. Several classification, diagnostic and screening criteria have been developed over the years, but there continues to be a need to develop criteria that reflect the current understanding of FM and are practical for use by clinicians and researchers. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration (FDA) and the American Pain Society (APS) initiated the ACTTION-APS Pain Taxonomy (AAPT) to develop a diagnostic system that would be clinically useful and consistent across chronic pain disorders. The AAPT established an international FM working group consisting of clinicians and researchers with expertise in FM to generate core diagnostic criteria for FM and apply the multidimensional diagnostic framework adopted by AAPT to FM. The process for developing the AAPT criteria and dimensions included literature reviews and synthesis, consensus discussions, and analyses of data from large population-based studies conducted in the United Kingdom. The FM working group established a revised diagnosis of FM and identified risk factors, course, prognosis, and pathophysiology of FM. Future studies will assess the criteria for feasibility, reliability, and validity. Revisions of the dimensions will also be required as research advances our understanding of FM. PERSPECTIVE: The ACTTION-APS FM taxonomy provides an evidence-based diagnostic system for FM. The taxonomy includes diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms. This approach might improve the recognition of FM in clinical practice.

Objective The effects of smoking on disease manifestations in axial SpA are inadequately described. Utilizing a large and well-characterized cohort, we investigated the association between smoking and extra-axial manifestations, and smoking and disease severity measures. Methods Baseline data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis were explored. Our analyses focused on extra-axial manifestations and other disease severity measures, including scales for fatigue, sleep, anxiety and depression. Logistic and linear models were used to quantify associations between disease characteristics according to smoking status (current/ex/never) and quantity (heavy/light), adjusting for age, gender, BMI, education, deprivation, comorbidities, symptom duration and alcohol status. Results A total of 2031 participants were eligible for the current analysis (68% male, mean age 49 years). Of these, 24% were current and 32% ex-smokers. When compared with non-smokers, current smokers had lower odds of uveitis [OR 0.7, 95% CI 0.5–0.9] and higher odds of psoriasis (ORadj 1.6, 95% CI 1.1–2.3). Ex- and current smokers had incrementally more severe disease than never smokers, with higher BASDAI (β = 0.3, 95% CI 0.1–0.6; β = 0.9, 95% CI 0.6–1.2) and BASFI (β = 0.5, 95% CI 0.2–0.8; β = 1.3, 95% CI 1.0–1.6); similar associations were observed for fatigue, sleep, anxiety and depression. Conclusion In this large cross-sectional study, we observed that smoking is independently associated with an adverse disease profile in axial SpA, including worse fatigue, sleep, anxiety and depression, and higher odds of psoriasis. The paradoxical association between current smoking and reduced odds of uveitis is interesting and warrants further investigation.

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.

ObjectiveWe 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.MethodsPRSs 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.ResultsIn 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.ConclusionsPRS 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.

Background/Aims There is evidence for non-pharmacological interventions to support patients to self-manage fatigue, however implementation in clinical practice is a challenge. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomised Trial) is a multi-centre three-arm randomised trial using a remotely delivered cognitive-behavioural approach (CBA) or personalized exercise programme (PEP) interventions, in addition to usual care, compared to normal care alone. Interventions were delivered to patients by rheumatology health professionals using a manual, after training. The aim of this nested qualitative evaluation was to understand their perspectives of delivering the interventions. Methods A subgroup of rheumatology healthcare professionals who had delivered the CBA and PEP interventions took part in semi-structured telephone interviews to explore their experiences of training and delivery, the challenges and benefits of learning new skills, and the barriers and facilitators to supporting patients remotely (mainly by telephone) using the LIFT manual. Results A total of 17 rheumatology healthcare professionals (13 women, 4 men) from the CBA (n = 9) and PEP (n = 8) arms contributed. SB conducted an inductive thematic analysis of the data set. ED, CA, AW and KL reviewed a sub-set of transcripts. Five main themes were identified: The benefits of informative, structured training: Rheumatology healthcare professionals reflected how training, including role-play, helped them to practice their skills, even though this could feel uncomfortable. Those allocated shorter four-hour training sessions would have liked more time to practice. Many felt anxious before meeting patients for the first time but liked the manual to refer to. Getting into the swing of it: Practice gave rheumatology healthcare professionals the confidence to tailor content to individual patients’ requirements. Clinical supervision in the PEP and CBA arm supported rheumatology healthcare professionals to query their own practice, gain valuable feedback, and request assistance where needed. Benefits of telephone delivery: The initial face-to-face session enabled rheumatology healthcare professionals to build rapport with patients. Thereafter, patients seemed engaged and valued the opportunity to address their fatigue and challenge their own beliefs via the telephone. Some patients not ready to change: Rheumatology healthcare professionals struggled to work collaboratively with a minority of patients who were not willing to make changes, lacked motivation to complete tasks or stopped engaging with the intervention. LIFT developing clinical skills: Rheumatology healthcare professionals were confident that they were doing the ‘right thing’ for patients with fatigue and gained professional satisfaction seeing patients’ fatigue improve. Many felt that the skills they acquired and their experiences of remote delivery were helping them to respond to the current COVID-19 related changes in service provision. Conclusion Findings support the value of skills training for rheumatology health professionals to deliver fatigue management interventions remotely. These insights can inform service provision and clinical practice. Disclosure S.E. Bennett: None. E. Dures: None. C. Almeida: None. E. Bachmair: None. K. Lovell: None. L. Paul: None. A. Wearden: None. G.J. Macfarlane: None. N. Basu: None.