Wendy Jenkins

Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study

Introduction Many doctors believe that patients with gout are unwilling to receive urate-lowering therapy (ULT) and blame them for poor adherence to management. Objective To test the effectiveness of a complex intervention for gout that incorporates key elements of current guidelines, including full patient information, delivered in an optimal setting (specialist hospital clinic). Method Observational study of patients reporting ongoing attacks of gout recruited from primary care lists. 106 participants (94 men, 12 women; mean age 61 years) were enrolled in the study. Patients received a predominantly nurse-delivered intervention that included education, individualised lifestyle advice and appropriate ULT. The predefined goal was to achieve serum uric acid (SUA) levels ≤360 μmol/l after 1 year in at least 70% of participants. Results Of the 106 participants at baseline, 16% had tophi; mean (SD) baseline SUA was 456 (98) µmol/l. All participants agreed to joint aspiration to confirm gout and all wished to receive ULT. At 12 months, 92% of the 106 participants had achieved the therapeutic target (SUA≤360 µmol); 85% had SUA <300 µmol/l. Allopurinol was the most commonly used ULT, requiring a median dose of 400 mg daily to achieve the target. Improvements in Short Form-36 were observed (significant for pain) after 1 year. Conclusion A predominantly nurse-led intervention including education, lifestyle advice and ULT can successfully achieve the recommended treatment target in more than 9 out of 10 patients. Full explanation and discussion about the nature of gout and its treatment options and individualisation of management probably account for this success.

History of knee surgery is associated with higher prevalence of neuropathic pain-like symptoms in patients with severe osteoarthritis of the knee

OBJECTIVE Neuropathic pain (NP) mechanisms contribute to the pain experience in osteoarthritis (OA). We aimed to characterise the factors that contribute to NP-like symptoms in knee OA patients. PATIENTS AND METHODS A total of 139 patients with knee OA were recruited from secondary care, and completed a nurse- administered PainDetect questionnaire (PD-Q ), a visual analogue scale (VAS) for pain intensity, and the Western Ontario MacMaster questionnaire (WOMAC). Cases with any previous history of total joint replacement were excluded. RESULTS Almost 75% of patients had non-zero PD-Q scores, and 34% had PD-Q scores corresponding to possible NP. No association was seen between PD-Q scores and duration of symptoms, gender, and radiographic severity. Possible NP was strongly associated (p < 1 × 10(-3)) with worse quality of life scores, worse sleep scores, higher pain intensity, worse WOMAC pain, stiffness and function scores. A history of previous knee surgery (arthroscopy, ligament repair or meniscectomy) was strongly associated with possible NP (odds ratio [OR] = 6.86; 95% CI = 1.78-26.43; p < 0.005). This association remained statistically significant after adjustment for pain intensity (OR = 6.37; 95% CI = 1.55-26.11; p < 0.010) whereas an association between history of knee surgery and the other measures of pain was found to be mediated by PD-Q scores. CONCLUSIONS NP-like symptoms are highly prevalent in patients with clinically severe painful OA and are a significant contributor to decreased quality of life and higher pain intensity. The cross-sectional association with previous history of knee surgery suggests that some of the NP-like symptoms may result from nerve damage.

Mild acetabular dysplasia and risk of osteoarthritis of the hip: a case–control study

Objective To determine whether mild variation in acetabular depth (AD) and shape is a risk factor for osteoarthritis (OA) of the hip. Methods The unaffected contralateral hip of patients with unilateral hip OA was compared with hips of asymptomatic controls without hip OA, derived from the Nottingham Genetics Osteoarthritis and Lifestyle case–control study. Standardised anteroposterior x-rays of the pelvis were used to measure centre edge (CE) angle and AD. Cut-off points for narrow CE angle and shallow AD were calculated from the control group (mean −1.96×SD). The relative risk of hip OA associated with each feature was estimated using OR and 95% CI and adjusted risks were calculated by logistic regression. Results In controls, both the CE angle and the AD were lower in the left hip than in the right hip. The CE angle related to age in both hips, and AD of the right hip was lower in men than in women. The contralateral unaffected hip in patients with unilateral hip OA had a decreased CE angle and AD compared with controls, irrespective of side. The lowest tertile of the CE angle in contralateral hips was associated with an eightfold risk of OA (aOR 8.06, 95% CI 4.87 to 13.35) and the lowest tertile of AD was associated with a 2.5-fold risk of OA (aOR 2.53, 95% CI 1.28 to 5.00). Significant increases in the risk of OA were also found as the CE angle and AD decreased. Conclusion Constitutional mild acetabular dysplasia appears to increase the risk of hip OA.

The British Society for Rheumatology Guideline for the Management of Gout

Gout is the most common cause of inflammatory arthritis worldwide. In UK general practice, the overall prevalence has increased from 1.4% in 1999 to 2.49% in 2012 [1], despite the availability of effective and potentially curative urate-lowering drugs for >50 years and evidence-based British and European management guidelines for nearly a decade [2, 3]. Clinical manifestations of gout resulting from monosodium urate crystal deposition include tophi, chronic arthritis, urolithiasis and renal disease as well as recurrent acute arthritis, bursitis and cellulitis. Gouty arthritis and tophi are associated with chronic disability, impairment of health-related quality of life [4 7], increased use of healthcare resources and reduced productivity [8]. Gout is also frequently associated with co-morbidities such as obesity, dyslipidaemia, diabetes mellitus, chronic renal insufficiency, hypertension, cardiovascular disease, hypothyroidism, anaemia, psoriasis, chronic pulmonary diseases, depression and OA [1] as well as with an increase in all-cause mortality (adjusted hazard ratio 1.13, 95% CI: 1.08, 1.18) and urogenital malignancy [1, 9]. Sustained hyperuricaemia is the single most important risk factor for the development of gout. Hyperuricaemia occurs secondarily to reduced fractional clearance of uric acid in> 90% of patients with gout [10]. Age, male gender, menopausal status in females, impairment of

Long-term persistence and adherence on urate-lowering treatment can be maintained in primary care-5-year follow-up of a proof-of-concept study

Objectives. To evaluate the persistence and adherence on urate‐lowering treatment (ULT) in primary care 5 years after an initial nurse‐led treatment of gout. Methods. One hundred gout patients initiated on up‐titrated ULT between March and July 2010 were sent a questionnaire that elicited information on current ULT, reasons for discontinuation of ULT if applicable, medication adherence and generic and disease‐specific quality‐of‐life measures in 2015. They were invited for one visit at which height and weight were measured and blood was collected for serum uric acid measurement. Results. Seventy‐five patients, mean age 68.13 years (s.d. 10.07) and disease duration 19.44 years (s.d. 13), returned completed questionnaires. The 5‐year persistence on ULT was 90.7% (95% CI 81.4, 91.6) and 85.3% of responders self‐reported taking ULT ≥6 days/week. Of the 65 patients who attended the study visit, the mean serum uric acid was 292.8 &mgr;mol/l (s.d. 97.2). Conclusion. An initial treatment that includes individualized patient education and involvement in treatment decisions results in excellent adherence and persistence on ULT >4 years after the responsibility of treatment is taken over by the patients general practitioner, suggesting that this model of gout management should be widely adopted.

OP0268 Nurse-led care versus general practitioner care of people with gout: a uk community-based randomised controlled trial

Background Despite increasing prevalence of gout in the UK (1), a variety of barriers result in suboptimal care (1,2) with only 40% of gout patients receiving urate-lowering therapy (ULT), usually at fixed dose without titration to a serum uric acid (SUA) target (1,2). Nurses successfully manage many chronic diseases in the community, and we have shown that when people with gout are fully informed and involved in management decisions uptake of ULT is high and subsequent adherence under nurse-led care is excellent (3). Objectives To directly compare nurse-led care to general practitioner (GP) care of people with gout in a 2 year randomised controlled trial (NIHR CRN Portfolio No.12943) Methods 517 participants with acute gout in the previous year were identified from 56 local GP practices and randomised to nurse-led or continuing GP care. The nurses were trained about gout and its management according to recommended best practice (EULAR and BSR guidelines) involving full information, addressing illness perceptions, and involving patients in management decisions. Assessments were undertaken at 1 and 2 years. Analysis was intention to treat (last observation carried forward). Results Nurse (n=255) and GP (n=262) groups were well matched at baseline for mean age (62 v 64yrs), sex (90% v 89% men), mean disease duration (11.6 v 12.7yrs), mean gout attack frequency in prior year (4.2 v. 3.8), tophi (13.7% v. 8.8%), mean SUA (443 v. 439 μmol/L), mean eGFR (71.5 v. 70.2) and ULT use (40% v. 39%) (all p>0.05). By 2yrs, 22 (8.6%) and 54 (20.6%) participants had discontinued the nurse and GP groups (p<0.001), including 2 v. 8 deaths respectively. Comparing nurse and GP groups at 2yrs: 95% v. 29% had SUA <360 μmol/L (primary outcome); 88% v. 16% had SUA <300 μmol/L; mean (SD) SUA was 252±73 v. 418±106; 97% v. 54% were on ULT; and mean (SD) dose of allopurinol was 470 (140) v. 240 (107) mg/day (all p<0.001). Mean (SD) attack frequency during the 2nd year was 0.33 (0.93) in the nurse v. 0.94 (2.03) in the GP group (p<0.001), and at 2yrs tophi were present in 2.6% (reduced) v. 9.6% respectively (p<002). Although equivalent at baseline, mean (SD) SF-36 norm-based physical component scores were better at 2yrs in the nurse group (41.31 (16.76) v. 37.87 (14.31); p<0.05). Conclusions Nurse-led care of people with gout in the UK community can result in high uptake and excellent adherence to ULT over a 2yr period, achievement of target SUA in >9/10 cases and consequent improvements in patient-centred outcomes and quality of life. This study reinforces the benefits of “treat-to-target”. Compared to standard GP care this model is likely to be cost effective long-term and merits further consideration. References Doherty M. et al. Ann Rheum Dis 2012;71:1765–70. Kuo C-F. et al. Ann Rheum Dis 2015;74:661–7. Rees F. et al. Ann Rheum Dis 2013:72:826–30. Acknowledgements Arthritis Research UK (Award No.19703) funded this study. Disclosure of Interest M. Doherty Grant/research support from: AstraZeneca, Consultant for: AstraZeneca, Grunenthal, Mallinckrodt and Roche, W. Jenkins: None declared, H. Richardson: None declared, A. Abhishek Grant/research support from: AstraZeneca, D. Ashton: None declared, C. Barclay: None declared, L. Duley: None declared, H. Jones: None declared, M. Santarelli: None declared, A. Sarmanova: None declared, M. Stevenson: None declared, W. Zhang Consultant for: AstraZeneca and Grunenthal

Use of prescription analgesic medication and pain catastrophizing after total joint replacement surgery

OBJECTIVE To survey the use of analgesic medication 4.8 years after total joint replacement (TJR) surgery and assess the determinants of medication usage. PATIENTS AND METHODS Of 852 patients who had undergone TJR for osteoarthritis were recruited from secondary care. Participants (mean age, 73.7 years) responded to a questionnaire on medication use, physical function and pain (WOMAC, VAS and body pain), pain catastrophizing and illness behaviour (somatization). RESULTS Only 37% of study participants were not on any pain relief medication, 25.1% were taking opioids, 6.9% were taking prescription NSAIDs and 25.9% were taking only non-prescription analgesics. Use of NSAIDs correlated with presence of back pain, body pain and high illness behaviour. The strongest associations with use of opioids were severe joint pain, high pain catastrophizing, body and back pain. After adjustment for covariates plus presence of pain, catastrophizing remained significantly associated with higher risk of opioid use (OR = 1.66, 95% CI: 1.13-2.43, p < 0.009) and of other prescription medication that can be used to treat pain (anti-depressants, anti-epileptics and hypnotics) (OR = 2.52, 95% CI: 1.61-3.95, p < 0.0005). CONCLUSIONS Use of opioid medication 4 years post-TJR is very high in our study population. In addition to joint, back and body pain, a major contributor to opioid use is pain catastrophizing. Our data suggest that current opioid and other analgesic prescribing patterns may benefit from considering the catastrophizing characteristics of patients.

Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene

Neuropathic pain-like joint symptoms (NP) are seen in a proportion of individuals diagnosed with osteoarthritis (OA) and post total joint replacement (TJR). In this study, we performed a genome-wide association study (GWAS) using NP as defined by the painDETECT questionnaire (score >12 indicating possible NP) in 613 post-TJR participants recruited from Nottinghamshire (UK). The prevalence of possible NP was 17.8%. The top four hits from the GWAS and two other biologically relevant single-nucleotide polymorphisms (SNPs) were replicated in individuals with OA and post TJR from an independent study in the same area (N=908) and in individuals from the Rotterdam Study (N=212). Three of these SNPs showed effect sizes in the same direction as in the GWAS results in both replication cohorts. The strongest association upon meta-analysis of a recessive model was for the variant allele in rs887797 mapping to the protein kinase C alpha (PRKCA) gene odds ratio (OR)possNP=2.41 (95% CI 1.74–3.34, P=1.29 × 10−7). This SNP has been found to be associated with multiple sclerosis and encodes a functional variant affecting splicing and expression of the PRKCA gene. The PRKCA gene has been associated with long-term potentiation, synaptic plasticity, chronic pain and memory in the literature, making this a biologically relevant finding.

Intercritical circulating levels of neo-epitopes reflecting matrixmetalloprotease-driven degradation as markers of gout and frequent gout attacks

OBJECTIVE Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares. METHODS Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples from 447 men with gout collected at baseline from an ongoing clinical trial, were analysed by ELISA for neo-epitopes from MMP degradation of collagens type I (C1M) and type III (C3M). The log10 levels of both markers were compared between cases and controls and between gout patients with three or more gout attacks in the past year and those with two or less attacks. RESULTS The circulating levels of C1M and C3M correlated with gout status in the case-control study. Levels of both markers were associated with frequent gout flares (⩾3 attacks in the past year) in both cohorts (odds ratio, OR = 3.1; 95% CI: 1.4, 6.8; P = 0.0056 for log10C1M, and OR = 6.7; 95% CI: 2.3, 19.3; P = 0.0005 for log10C3M). The area under the curve in a receiver operating characteristic analysis of frequent flares increased from 0.68 to 0.74 in one cohort and from 0.60 to 0.66 in the other when log10C1M and log10C3M were added to clinical variables of the model. CONCLUSION C1M and C3M, reflective of interstitial matrix destruction, are associated with gout status and with frequent gout flares in men, suggesting that increased MMP activity may contribute to gout flares. Further research is needed to find out whether this is independent of dietary and lifestyle risk factors for acute gout.

Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial

Summary Background In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community. Methods Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 μmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346. Findings 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 μmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42–4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years. Interpretation Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes. Funding Arthritis Research UK.