M Lunt

Publications (81)416.5 Total impact

• Article: Enrichment of vitamin D response elements in RA-associated loci supports a role for vitamin D in the pathogenesis of RA.

  A Yarwood, P Martin, J Bowes, M Lunt, J Worthington, A Barton, S Eyre
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  ABSTRACT: The aim of this study was to explore the role of vitamin D in rheumatoid arthritis (RA) pathogenesis by investigating the enrichment of vitamin D response elements (VDREs) in confirmed RA susceptibility loci and testing variants associated with vitamin D levels for association with RA. Bioinformatically, VDRE genomic positions were overlaid with non-HLA (human leukocyte antigen)-confirmed RA susceptibility regions. The number of VDREs at RA loci was compared to a randomly selected set of genomic loci to calculate an average relative risk (RR). Single-nucleotide polymorphisms (SNPs) in the DHCR7/NADSYN1 (nicotinamide adenine dinucleotide synthase 1) and CYP2R1 loci, previously associated with circulating vitamin D levels, were tested in UK RA cases (n=3870) and controls (n=8430). Significant enrichment of VDREs was seen at RA loci (P=9.23 × 10(-8)) when regions were defined either by gene (RR 5.50) or position (RR 5.86). SNPs in the DHCR7/NADSYN1 locus showed evidence of positive association with RA, rs4944076 (P=0.008, odds ratio (OR) 1.14, 95% confidence interval (CI) 1.03-1.24). The significant enrichment of VDREs at RA-associated loci and the modest association of variants in loci-controlling levels of circulating vitamin D supports the hypothesis that vitamin D has a role in the development of RA.Genes and Immunity advance online publication, 2 May 2013; doi:10.1038/gene.2013.23.
  Genes and immunity 05/2013; · 4.22 Impact Factor
• Article: Morbid obesity is associated with disability in early inflammatory polyarthritis: Results from the Norfolk Arthritis Register (NOAR).

  Jh Humphreys, Smm Verstappen, H Mirjafari, D Bunn, M Lunt, In Bruce, Dpm Symmons
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  ABSTRACT: OBJECTIVES: Obesity has been associated with disease outcomes in inflammatory arthritis. This study aimed to investigate cross-sectionally the relationship between body mass index (BMI) and functional disability in a large inception cohort of patients with early inflammatory polyarthritis (IP) METHODS: Patients age ≥16 with ≥2 swollen joints for ≥4 weeks were recruited into the Norfolk Arthritis Register (NOAR). At initial assessment, clinical and demographic data were obtained; joints examined, and height and weight measured. Blood samples were taken to measure inflammatory markers and autoantibodies, and patients completed the Health Assessment Questionnaire (HAQ) to assess functional disability. Univariate and multivariate ordinal regression were used to examine the cross-sectional association between BMI and HAQ. Multiple imputation using chained equations allowed inclusion of patients with missing variables. RESULTS: 1246 patients were studied, median age 57 years. 782 (63%) patients were female, 303 (25%) were obese (BMI ≥30 kg/m(2) ). Morbid obesity (BMI ≥35) was significantly associated with worse functional disability in the univariate and multivariate analysis with missing data imputed, adjusting for age, gender, symptom duration, smoking status, disease activity, autoantibodies, comorbidities and treatment(multivariate OR=1.87, 95% CI 1.14-3.07). CONCLUSIONS: Morbid obesity in patients with early IP is associated with worse HAQ scores. This should be taken into account in patient management and when interpreting HAQ in clinical practice. © 2012 by the American College of Rheumatology.
  Arthritis care & research. 05/2012;
• Article: Multiple adverse pregnancy outcomes before symptom onset are associated with a worse disease outcome in women with recent-onset inflammatory polyarthritis.

  E M Camacho, S M M Verstappen, M Lunt, D K Bunn, D P M Symmons
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  ABSTRACT: Previous evidence suggests that women with a history of adverse pregnancy outcomes (APOs) may be at greater risk of developing rheumatoid arthritis. Additionally, one study reported that female patients with rheumatoid arthritis with a history of preonset APOs showed a worse 2-year radiographic outcome than did patients with no APOs. The authors' aim was to investigate the relationship between preonset APOs (spontaneous abortion or stillbirth) and disease outcome in women with inflammatory polyarthritis (IP). The Norfolk Arthritis Register (NOAR) is a primary-care-based cohort of patients with recent-onset IP; 1586 gravid women who joined NOAR during 1990-2004 were included in this analysis. The authors examined the relationship between patient-reported preonset APOs and disease outcome, measured using the Health Assessment Questionnaire (HAQ) and disease activity score in 28 joints (DAS28(CRP)) (for a subgroup of patients), using linear random effects analysis, adjusted for age and other factors. In a predominantly parous cohort (99%), 397 (25%) women reported ≥1 APO before symptom onset. The rates of APOs in NOAR were comparable to the general population. On average, women with a history of ≥2 APOs had significantly higher HAQ and DAS28 scores over time than women with no APOs (mean difference in HAQ 0.13 (95% CI 0.002 to 0.26); DAS28, 0.56 (95% CI 0.01 to 1.11)). This relationship was more pronounced in women with ≥3 APOs (mean difference in HAQ 0.23 (95% CI 0.02 to 0.43); DAS28, 0.98 (95% CI 0.23 to 1.74)). Women with two or more APOs before IP onset had a worse disease outcome than women with no APOs.
  Annals of the rheumatic diseases 04/2012; 71(4):528-33. · 8.11 Impact Factor
• Article: MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms.

  S A Owen, M Lunt, J Bowes, S L Hider, I N Bruce, W Thomson, A Barton
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  ABSTRACT: Association of two key variants mapping to the MTHFR gene (C677T (rs1801133) and A1298C (rs1801131)) with response to methotrexate (MTX) remains controversial. We investigated these and other markers spanning the gene as predictors of MTX efficacy and adverse events in a UK rheumatoid arthritis (RA) patient cohort and performed a meta-analysis of the two key variants using all published data. The tagging single nucleotide polymorphisms (SNPs) were genotyped in 309 patients with well-defined outcomes to MTX treatment and 17 studies were included in the meta-analysis. No association of the SNPs tested was detected with MTX efficacy or toxicity in our UK cohort. After combining our data with previous studies by meta-analysis, the random effects pooled odds ratios (OR) for both C677T and A1298C showed no association with efficacy or toxicity for either of the SNPs (efficacy: OR=1.05 (95% confidence interval (CI) 0.83-1.32) and OR=0.81 (95% CI 0.53-1.24), respectively; toxicity: OR=1.38 (95% CI 0.90-2.12) and OR=1.19 (95% CI 0.80-1.78), respectively). The available evidence suggests that the MTHFR C677T and A1298C gene polymorphisms are not reliable predictors of response to MTX treatment in RA patients.The Pharmacogenomics Journal advance online publication, 20 September 2011; doi:10.1038/tpj.2011.42.
  The Pharmacogenomics Journal 09/2011; · 4.54 Impact Factor
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  Available from: PubMed Central

  Article: Risk of septic arthritis in patients with rheumatoid arthritis and the effect of anti-TNF therapy: results from the British Society for Rheumatology Biologics Register.

  J B Galloway, K L Hyrich, L K Mercer, W G Dixon, A P Ustianowski, M Helbert, K D Watson, M Lunt, D P M Symmons
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  ABSTRACT: To evaluate the risk of septic arthritis (SA) in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, the authors compared the risk of SA between 11 881 anti-TNF-treated and 3673 non-biological disease-modifying antirheumatic drug (nbDMARD)-treated patients. 199 patients had at least one episode of SA (anti-TNF: 179, nbDMARD: 20). Incidence rates were: anti-TNF 4.2/1000 patient years (pyrs) follow-up (95% CI 3.6 to 4.8), nbDMARD 1.8/1000 pyrs (95% CI 1.1 to 2.7). The adjusted HR for SA in the anti-TNF cohort was 2.3 (95% CI 1.2 to 4.4). The risk did not differ significantly between the three agents: adalimumab, etanercept and infliximab. The risk was highest in the early months of therapy. The patterns of reported organisms differed in the anti-TNF cohort. Prior joint replacement surgery was a risk factor for SA in all patients. The rate of postoperative joint infection (within 90 days of surgery) was 0.7%. This risk was not significantly influenced by anti-TNF therapy. Anti-TNF therapy use in RA is associated with a doubling in the risk of SA. Physicians and surgeons assessing the RA patient should be aware of this potentially life-threatening complication.
  Annals of the rheumatic diseases 07/2011; 70(10):1810-4. · 8.11 Impact Factor
• Article: The relationship between oral contraceptive use and functional outcome in women with recent-onset inflammatory polyarthritis: results from the Norfolk Arthritis Register.

  E M Camacho, M Lunt, T M Farragher, S M M Verstappen, D K Bunn, D P M Symmons
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  ABSTRACT: Use of oral contraceptives (OCs) may prevent the development of rheumatoid arthritis, but the influence of OC use on disease outcome is unresolved. The purpose of this study was to examine functional outcome and OC use in women with inflammatory polyarthritis (IP). The Norfolk Arthritis Register (NOAR) is an inception cohort of patients with recent-onset IP. We studied patient-reported history of OC use in 663 women who were born after 1945 and who had not used OCs during followup. OC use during followup was additionally investigated in 265 women who were <50 years old and had not undergone menopause or hysterectomy during followup. All patients were recruited to the NOAR between 1990 and 2004. Functional ability was assessed using the Health Assessment Questionnaire (HAQ), with adjustment for age at symptom onset. The median followup was 4.9 years. In the investigation analyzing OC use before symptom onset, patients who had used OCs before symptom onset had lower HAQ scores throughout followup than patients who had not taken OCs before symptom onset (difference in score at 5-year followup -0.35; 95% confidence interval [95% CI] -0.51, -0.19). Patients who were taking OCs at baseline had lower HAQ scores over time than women who were not taking OCs at baseline but had previously done so (mean difference -0.21; 95% CI -0.40, -0.02). In the investigation analyzing OC use during followup, OC use during followup was associated with lower HAQ scores over time than no OC use during followup (mean difference -0.06; 95% CI -0.16, 0.03); however, this was only significant for women with moderate or severe functional disability at the previous assessment (mean difference -0.23; 95% CI -0.40, -0.07). Further adjustment for potential confounders and exclusion of hormone replacement therapy users had little impact. OC use is generally associated with a beneficial functional outcome in IP, and use before and at symptom onset appeared to have the most consistent benefit.
  Arthritis & Rheumatism 04/2011; 63(8):2183-91. · 7.87 Impact Factor
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  Available from: PubMed Central

  Article: Parity, time since last live birth and long-term functional outcome: a study of women participating in the Norfolk Arthritis Register.

  E M Camacho, M Harrison, T M Farragher, M Lunt, D K Bunn, S M M Verstappen, D P M Symmons
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  ABSTRACT: To investigate the relationship between pre-symptom onset live births and functional outcome in women with inflammatory polyarthritis (IP). 1872 women with no subsequent pregnancies were registered with the Norfolk Arthritis Register between 1990 and 2004 and followed-up for a median of 5 years. Functional disability over time was assessed by Health Assessment Questionnaire (HAQ). The number and calendar year of past live births were recorded. Differences in HAQ score over time by parity and time since last live birth (latency), adjusted for age and symptom duration, were examined using linear random effects models. The results were then adjusted for a number of potential confounders. 1553 women (83%) had ≥1 live births before symptom onset. The median latency was 26 years (IQR 16-35). Parous women had significantly lower HAQ scores over time than nulliparous women (-0.19, 95% CI -0.32 to -0.06). Increasing latency was associated with increasing HAQ score; the mean HAQ score of women with a latency of approximately 32 years was the same as for nulliparous women. This was independent of autoantibody status, socioeconomic status, smoking history and comorbidity. Parous women who develop IP have better functional outcome over time than nulliparous women who develop IP. The beneficial effect of parity diminishes with time.
  Annals of the rheumatic diseases 04/2011; 70(4):642-5. · 8.11 Impact Factor
• Article: Testing pharmacogenetic indices to predict efficacy and toxicity of methotrexate monotherapy in a rheumatoid arthritis patient cohort.

  S A Owen, M Lunt, S L Hider, I N Bruce, A Barton, W Thomson
  Arthritis & Rheumatism 12/2010; 62(12):3827-9. · 7.87 Impact Factor
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  Available from: PubMed Central

  Article: The relationship between post-onset pregnancy and functional outcome in women with recent onset inflammatory polyarthritis: results from the Norfolk Arthritis Register.

  E M Camacho, T M Farragher, M Lunt, S M M Verstappen, D Bunn, D P M Symmons
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  ABSTRACT: To examine the influence of post-symptom-onset pregnancy on disease outcome in women with inflammatory polyarthritis (IP). A total of 631 women, aged <48 years at symptom onset, were registered with the Norfolk Arthritis Register (NOAR) between 1990 and 2004. Functional disability was assessed using the Stanford Health Assessment Questionnaire (HAQ). Blood was tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA). The date and outcome of all pregnancies were reported during a median follow-up of 7 years. Linear random effects models were used to examine HAQ score over time, by pregnancy status. were then stratified for RF and ACPA status. Results In all, 72 women had a post-onset pregnancy (Po-P) including 45 women who were pregnant at a follow-up assessment. Pregnancy was generally associated with lower HAQ scores over time than non-pregnancy. The 10 ACPA-positive women who had a Po-P had significantly worse subsequent HAQ scores. Overall, Po-P is associated with lower HAQ scores, compared to no Po-P. This may reflect a beneficial effect of pregnancy on disease outcome, or that predominantly women with milder disease become pregnant. In women with the worst predicted outcome (APCA positive), Po-P is associated with a worse outcome than no pregnancy.
  Annals of the rheumatic diseases 10/2010; 69(10):1834-7. · 8.11 Impact Factor
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  Available from: PubMed Central

  Article: Influence of anti-TNF therapy on mortality in patients with rheumatoid arthritis-associated interstitial lung disease: results from the British Society for Rheumatology Biologics Register.

  W G Dixon, K L Hyrich, K D Watson, M Lunt, D P M Symmons
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  ABSTRACT: Anti-tumour necrosis factor (anti-TNF) therapy has been associated with reports of rapid severe progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, reports also exist of favourable responses to anti-TNF therapy in patients with ILD. The aim of this study was to examine the influence of anti-TNF therapy on mortality in patients with pre-existing RA-ILD. Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, 367 patients with pre-existing RA-ILD were identified (299 treated with anti-TNF therapy and 68 treated with traditional disease-modifying antirheumatic drugs (DMARDs)). 70/299 patients (23%) in the anti-TNF cohort died after a median follow-up of 3.8 years compared with 14/68 (21%) in the DMARD cohort after a median follow-up of 2.1 years. The mortality was 68 deaths/1000 person years (pyrs) (95% CI 53 to 86) in the anti-TNF cohort and 92/1000 pyrs (95% CI 50 to 155) in the DMARD cohort, generating an age- and sex-adjusted mortality rate ratio (aMRR) of 1.26 (95% CI 0.69 to 2.31). After further adjustment for potential confounders, the aMRR fell to 0.81 (95% CI 0.38 to 1.73) for the anti-TNF cohort compared with the DMARD cohort. RA-ILD was the underlying cause of death in 15/70 (21%) and 1/14 (7%) patients in the anti-TNF and DMARD cohorts, respectively. The mortality in patients with RA-ILD is not increased following treatment with anti-TNF therapy compared with traditional DMARDs. The proportion of deaths attributable to RA-ILD is higher in patients treated with anti-TNF therapy, although reporting bias may exist.
  Annals of the rheumatic diseases 06/2010; 69(6):1086-91. · 8.11 Impact Factor
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  Available from: PubMed Central

  Article: Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register.

  W G Dixon, K D Watson, M Lunt, L K Mercer, K L Hyrich, D P M Symmons
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  ABSTRACT: To explore the influence of anti-tumor necrosis factor (anti-TNF) therapy upon the incidence of cancer in patients with rheumatoid arthritis (RA) and prior malignancy. Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study established in 2001, we identified 293 patients with a prior malignancy from over 14,000 patients with RA. We compared rates of incident malignancy in 177 anti-TNF-treated patients and 117 patients with active RA treated with traditional disease-modifying antirheumatic drugs (DMARDs), all with prior malignancy. One patient switched therapy and contributed to both cohorts. The rates of incident malignancy were 25.3 events/1,000 person-years in the anti-TNF cohort and 38.3/1,000 person-years in the DMARD cohort, generating an age- and sex-adjusted incidence rate ratio of 0.58 (95% confidence interval 0.23-1.43) for the anti-TNF-treated cohort compared with the DMARD cohort. Of the patients with prior melanomas, 3 (18%) of 17 in the anti-TNF cohort developed an incident malignancy, compared with 0 of 10 in the DMARD cohort. The way in which UK rheumatologists are selecting patients with RA and prior malignancy to receive anti-TNF therapy is not leading to an increased risk of incident malignancy. Although reassuring, these results should not be interpreted as indicating that it is safe to treat all RA patients with prior malignancy with anti-TNF therapy.
  Arthritis care & research. 06/2010; 62(6):755-63.
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  Available from: PubMed Central

  Article: Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR).

  W G Dixon, K L Hyrich, K D Watson, M Lunt, J Galloway, A Ustianowski, D P M Symmons
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  ABSTRACT: The risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) is thought to be increased following anti-tumour necrosis factor (anti-TNF) therapy, with a proposed differential risk between the anti-TNF drugs etanercept (ETA), infliximab (INF) and adalimumab (ADA). To compare directly the risk between drugs, to explore time to event, site of infection and the role of ethnicity. Data from the British Society for Rheumatology Biologics Register (BSRBR), a national prospective observational study, were used to compare TB rates in 10 712 anti-TNF treated patients (3913 ETA, 3295 INF, 3504 ADA) and 3232 patients with active RA treated with traditional disease-modifying antirheumatic drugs. To April 2008, 40 cases of TB were reported, all in the anti-TNF cohort. The rate of TB was higher for the monoclonal antibodies ADA (144 events/100,000 person-years) and INF (136/100,000 person-years) than for ETA (39/100,000 person-years). After adjustment, the incidence rate ratio compared with ETA-treated patients was 3.1 (95% CI 1.0 to 9.5) for INF and 4.2 (1.4 to 12.4) for ADA. The median time to event was lowest for INF (5.5 months) compared with ETA (13.4 months) and ADA (18.5 months). 13/40 cases occurred after stopping treatment. 25/40 (62%) cases were extrapulmonary, of which 11 were disseminated. Patients of non-white ethnicity had a sixfold increased risk of TB compared with white patients treated with anti-TNF therapy. The rate of TB in patients with RA treated with anti-TNF therapy was three- to fourfold higher in patients receiving INF and ADA than in those receiving ETA.
  Annals of the rheumatic diseases 10/2009; 69(3):522-8. · 8.11 Impact Factor
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  Available from: PubMed Central

  Article: Effects of switching between anti-TNF therapies on HAQ response in patients who do not respond to their first anti-TNF drug.

  K L Hyrich, M Lunt, W G Dixon, K D Watson, D P M Symmons
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  ABSTRACT: Small studies have shown an improvement in disease activity in patients with RA who have switched between anti-TNF therapies for reasons of inefficacy. However, it is not clear whether switching improves longer term outcomes, such as disability. This analysis compares changes in HAQ scores 1 yr following lack of response to a first anti-TNF based on subsequent treatment during that year. Analysis was limited to RA patients with inefficacy to a first anti-TNF based on (i) clinician opinion and/or (ii) disease activity score in 28 joints and had an HAQ measured at time of non-response and 12 months later. Patients were classified into three groups based on treatment during the next 12 months: (i) continued anti-TNF despite non-response; (ii) stopped anti-TNF with no further biologics; and (iii) switched to a second anti-TNF. Mean improvement in HAQ was compared among the groups using multivariable linear regression models. As of July 2006, 868 patients met the inclusion for this analysis. Four hundred and seventy-nine patients stopped anti-TNF of whom 331 switched to a second anti-TNF. Three hundred and eighty-nine continued treatment. Patients who continued and those who switched had improvements in HAQ over the 12 months, unlike patients who discontinued all biologic therapy. The best improvement was seen in those who switched [adjusted mean improvement in HAQ 0.15 (95% CI 0.26, 0.05)]. There is a significant improvement in HAQ in patients who switch to a second anti-TNF, providing an effective next choice of therapy for some patients who fail to respond to their first anti-TNF.
  Rheumatology (Oxford, England) 08/2008; 47(7):1000-5. · 4.24 Impact Factor
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  Available from: PubMed Central

  Article: Association between duration of symptoms and severity of disease at first presentation to paediatric rheumatology: results from the Childhood Arthritis Prospective Study.

  N Adib, K Hyrich, J Thornton, M Lunt, J Davidson, J Gardner-Medwin, H Foster, E Baildam, L Wedderburn, W Thomson
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  ABSTRACT: To study the association between disease severity at first presentation to paediatric rheumatology (PRh) and length of time since symptom onset in children recruited to the Childhood Arthritis Prospective Study. Children <or=16 yrs with inflammatory arthritis persisting >or=2 weeks were recruited from five UK hospitals. Data including demographics, disease features, Childhood Health Assessment Questionnaire (CHAQ), physician and parent global assessment and blood tests were collected at the first appointment with PRh (baseline). The association between symptom duration (defined as time from first reported symptom onset to presentation at PRh) and baseline disease characteristics was evaluated using non-parametric descriptive statistics and multivariable logistic regression analyses. Five hundred and seven children (65% female) were included: median age at onset was 6.8 yrs. Two hundred and thirty-three had oligoarthritis, 68 had RF-negative polyarthritis, 27 had systemic onset arthritis and 29 had arthritis that was not JIA. The median symptom duration was 4.6 months. Median symptom duration was shortest for children presenting with systemic arthritis (1.6 months) and longest for those with PsA (8.6 months). Children with a longer duration of symptoms were older and had higher median active joint counts but lower median ESR. Symptom duration did not correlate with CHAQ score at presentation. Children who have systemic arthritis had the shortest delay to PRh presumably because they are profoundly unwell. Children with joint pain/stiffness but normal ESR had longer delays suggesting that if blood tests do not indicate inflammation, the diagnosis of JIA may be overlooked.
  Rheumatology (Oxford, England) 07/2008; 47(7):991-5. · 4.24 Impact Factor
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  Available from: PubMed Central

  Article: Costing juvenile idiopathic arthritis: examining patient-based costs during the first year after diagnosis.

  J Thornton, M Lunt, D M Ashcroft, E Baildam, H Foster, J Davidson, J Gardner-Medwin, M W Beresford, D Symmons, W Thomson, R A Elliott
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  ABSTRACT: There are few data on the treatment patterns and associated cost of treating children with inflammatory arthritis including juvenile idiopathic arthritis (JIA), in the short or long term. The aim of this study was to obtain patient-based costs for treating children with JIA in the UK, in the first year from diagnosis and from the secondary health care payer perspective. The Childhood Arthritis Prospective Study (CAPS) is an ongoing longitudinal study recruiting children with inflammatory arthritis from four UK hospital centres. Included children are newly diagnosed, <or=16 years old with inflammatory arthritis of one or more joints, which has persisted for at least 2 weeks. Health service resource use data were collected as part of routine clinical care at study entry, 6 months and 1 year. Reference unit costs were applied to these data and the cost of treatment per child calculated for the first year from diagnosis. A total of 297 children attended a 12-month follow-up visit. The mean annual total cost per child was pound1649 (s.d. pound1093, range pound401- pound6967). The highest cost component was for appointments with paediatric rheumatologists. Mean total costs were highest for children with enthesitis-related, systemic JIA or extended oligoarthritis. In the first 12 months after diagnosis, children with all JIA disease subtypes consume large, but highly variable quantities of health service resources. Individual patient costs are required to reflect the wide variation in cost between patients and allow appropriate recouping of costs for contracted services and for assessing the economic impact of interventions.
  Rheumatology (Oxford, England) 07/2008; 47(7):985-90. · 4.24 Impact Factor
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  Available from: vu.nl

  Article: Impact of prevalent and incident vertebral fractures on utility: results from a patient-based and a population-based sample.

  N M van Schoor, S K Ewing, T W O'Neill, M Lunt, J H Smit, P Lips
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  ABSTRACT: Data are scarce on the impact of vertebral fractures (VFX) on utility. The objective of this study was to assess the impact of prevalent and incident VFX on utility in both a patient-based and population-based sample. Data from the Multiple Outcomes of Raloxifene Evaluation (MORE) study (n = 550 for prevalent VFX and n = 174 for incident VFX) and the European Prospective Osteoporosis Study (EPOS) (n = 236) were used. Utility was assessed by the index score of the EQ-5D. In the MORE study, highly statistically significant associations were found between utility and the presence of prevalent VFX (p < 0.001), number of prevalent VFX (p < 0.001), severity of prevalent VFX (p < 0.001), the combination of number and severity of prevalent VFX (p = 0.001) and location of prevalent VFX (p = 0.019). The mean utility was significantly lower among women who suffered an incident VFX (utility = 0.67) than among women who did not (utility = 0.77) (p = 0.005), although utility loss was not significantly different between the two groups (p = 0.142). In EPOS, the combination of number and severity of incident VFX was significantly related to utility (p = 0.030). In conclusion, utility is lower among persons with prevalent and incident VFX, especially in a patient-based sample. Utility loss was not significantly different between women without and with incident VFX.
  Quality of Life Research 03/2008; 17(1):159-67. · 2.30 Impact Factor
• Article: Five-year outcome of a primary-care-based inception cohort of patients with inflammatory polyarthritis plus psoriasis.

  C Morgan, M Lunt, D Bunn, D G I Scott, D P M Symmons
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  ABSTRACT: To establish whether patients with inflammatory arthritis plus psoriasis have a different outcome from those who do not have psoriasis. Seventy-nine patients with inflammatory arthritis plus psoriasis were recruited by the Norfolk Arthritis Register (NOAR) in 1990-94 and followed for 5 yrs. Their outcome was compared with the remainder (n = 755) of the NOAR cohort. We then restricted the analysis to subjects who were rheumatoid factor (RF)-negative, and compared those with and without psoriasis. Outcomes studied included remission, deformed joint count, the presence and extent of erosive damage and physical function. Patients with psoriasis were younger, more likely to be male, less likely to be RF-positive and more likely to have been treated with disease-modifying drugs than patients without psoriasis. After adjustment for age, gender and treatment, the only differences between the psoriasis and non-psoriasis groups were in RF positivity (adjusted odds ratio 0.44; 95% CI 0.25, 0.78) and in the Larsen score in patients with erosions. Patients with inflammatory arthritis plus psoriasis have a similar outcome to other RF-negative patients with arthritis.
  Rheumatology (Oxford, England) 01/2008; 46(12):1819-23. · 4.24 Impact Factor
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  Available from: PubMed Central

  Article: Serious infection following anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis: lessons from interpreting data from observational studies.

  W G Dixon, D P M Symmons, M Lunt, K D Watson, K L Hyrich, A J Silman
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  ABSTRACT: In a recent observational study, we found that the risk of serious infection following anti-tumor necrosis factor alpha (anti-TNFalpha) therapy in patients with rheumatoid arthritis (RA) was not importantly increased compared with the background risk in routinely treated RA patients with similar disease severity. Observational data sets are, however, subject to a number of important biases related to selection factors for the timing of starting and stopping therapy. Infection risk is also likely to vary with duration of therapy. This study was undertaken to examine the influences of these biases and of the method of analysis on the risk of infection. We compared the risk of serious infection in 8,659 patients treated with anti-TNFalpha with that in 2,170 patients treated with traditional disease-modifying antirheumatic drugs (DMARDs) recruited to the British Society for Rheumatology Biologics Register. We applied a number of statistical models in which we varied the length of the followup period by using different definitions of the date of discontinuation of treatment and different lag periods of risk following drug cessation. When the at-risk period was defined as "receiving treatment", the adjusted incidence rate ratio comparing patients receiving anti-TNFalpha therapy with patients receiving DMARD therapy was 1.22 (95% confidence interval [95% CI] 0.88-1.69). Limiting followup to the first 90 days, however, revealed an adjusted incidence rate ratio of 4.6 (95% CI 1.8-11.9). Rates of infection were increased in the 90 days immediately following drug discontinuation and beyond, explained by selection factors for drug discontinuation. These findings show that overall, the way in which UK rheumatologists select patients for starting and discontinuing anti-TNFalpha therapy explains our previous finding of no increase in risk. However, there may be important increases in true risk, notably early in the course of treatment, that would become more evident depending on the definition of at-risk period.
  Arthritis & Rheumatism 10/2007; 56(9):2896-904. · 7.87 Impact Factor
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  Available from: PubMed Central

  Article: Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register.

  W G Dixon, K D Watson, M Lunt, K L Hyrich, A J Silman, D P M Symmons
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  ABSTRACT: Rheumatoid arthritis (RA) is associated with an increased risk of coronary artery disease, possibly acting via shared mechanisms of inflammation. This study was undertaken to test the hypothesis that the powerful antiinflammatory effect of anti-tumor necrosis alpha (anti-TNFalpha) therapy might lead to a reduction in the incidence of myocardial infarction (MI) in patients with RA. Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, we compared MI rates in 8,670 patients with RA treated with anti-TNFalpha and 2,170 patients with active RA treated with traditional disease-modifying antirheumatic drugs (DMARDs). Through July 2006, 63 MIs occurred in the anti-TNFalpha cohort during 13,233 person-years of followup and 17 MIs occurred in the DMARD cohort during 2,893 person-years of followup, equivalent to a rate of 4.8 events per 1,000 person-years and 5.9 events per 1,000 person-years, respectively. After adjustment for baseline risk factors, there was no reduction in the rate of MI in the anti-TNFalpha cohort compared with the DMARD cohort (incidence rate ratio 1.44 [95% confidence interval 0.56-3.67]). In an analysis of anti-TNFalpha-treated patients who responded to the treatment within 6 months versus those who did not, MI rates were found to be 3.5 events per 1,000 person-years in responders and 9.4 events per 1,000 person-years in nonresponders. The adjusted incidence rate ratio (95% confidence interval) for responders compared with nonresponders was 0.36 (0.19-0.69). These results indicate that RA patients treated with anti-TNFalpha do not have a lower incidence of MI compared with RA patients treated with traditional DMARDs. However, the risk of MI is markedly reduced in those who respond to anti-TNFalpha therapy by 6 months compared with nonresponders. This finding supports the notion that inflammation plays a pivotal role in MI.
  Arthritis & Rheumatism 10/2007; 56(9):2905-12. · 7.87 Impact Factor
• Article: Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype.

  Y Ahmad, J Shelmerdine, H Bodill, M Lunt, M G Pattrick, L S Teh, R M Bernstein, M G Walker, I N Bruce
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  ABSTRACT: We aimed to examine the strength of association between traditional cardiovascular risk factors and carotid plaque development in systemic lupus erythematosus (SLE) patients and controls. We also aimed to determine which lupus-related factors are associated with carotid plaque and whether SLE sensitizes patients to the effects of traditional factors. We studied 200 women with SLE and 100 controls. Demographic and risk factor data were collected and SLE features, including autoantibody profiles and therapy were noted. All subjects had B- mode ultrasound of their carotid arteries examined for the presence and distribution of plaque. SLE patients <55 years old had more plaque (21% vs 3% P < 0.01) and more SLE patients had plaque in the internal carotid artery (11% vs 4%; P < 0.05). Traditional risk factor models performed less well in SLE compared with controls [area under Receiver Operator Characteristic curves (AUC ROC) = 0.76 vs 0.90; P < 0.01]. A multivariable model using SLE factors only, performed significantly better (AUC ROC = 0.87; P < 0.01). The final model in SLE included age and cigarette pack-years smoking as well as azathioprine exposure ever, antiphospholipid antibodies (APLA) and previous arterial events (AUC ROC = 0.88). SLE patients have a higher prevalence and different distribution of carotid plaque than controls. SLE factors perform significantly better than traditional risk factors in their association with atherosclerosis in SLE and these factors add to the influence of traditional risk factors rather than sensitizing lupus patients to traditional factors. The SLE phenotype helps identify patients at increased risk of atherosclerosis.
  Rheumatology 07/2007; 46(6):983-8. · 4.06 Impact Factor