Kings Mill Center

King's Lynn, United Kingdom

Kings Mill Center

King's Lynn, United Kingdom
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Mercer L.K.,University of Manchester | Galloway J.B.,King's College London | Lunt M.,University of Manchester | Davies R.,University of Manchester | And 34 more authors.
Annals of the Rheumatic Diseases | Year: 2017

Objectives Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma compared with the general population. There are concerns that tumour necrosis factor inhibitors (TNFi) may exacerbate this risk. However, since the excess risk of lymphoma in RA is related to the cumulative burden of inflammation, TNFi may conversely reduce the risk of lymphoma by decreasing the burden of inflammation. The aim of this study was to compare the risk of lymphoma in subjects with RA treated with TNFi with those treated with non-biological therapy. Methods Subjects diagnosed by a rheumatologist with RA enrolled in the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective cohort study, were followed until first lymphoma, death or until 30 November 2013. Rates of lymphoma in the TNFi and non-biological-treated cohorts were compared using Cox regression. Results 11 931 TNFi-treated patients were compared with 3367 biological-naive patients. 84 lymphomas (88 (95% CI 70 to 109) per 100 000 person-years) were reported in the TNFi cohort and 30 lymphomas (154 (95% CI 104 to 220)) in the biological-naive cohort. After adjusting for differences in baseline characteristics, there was no difference in the risk of lymphoma for the TNFi versus the biological-naive group: HR 1.00 (95% CI 0.56 to 1.80). No risk differences were observed for individual TNFi. Conclusions In medium-term follow-up, there is no evidence that tumour necrosis factor inhibition influences the risk of lymphoma over the background risk in subjects with RA. © Published by the BMJ Publishing Group Limited.


Low A.S.L.,University of Manchester | Symmons D.P.M.,University Institute of Health Sciences | Lunt M.,University of Manchester | Mercer L.K.,University of Manchester | And 34 more authors.
Annals of the Rheumatic Diseases | Year: 2017

Objectives Patients with rheumatoid arthritis (RA) are at increased risk of myocardial infarction (MI) compared with subjects without RA, with the increased risk driven potentially by inflammation. Tumour necrosis factor inhibitors (TNFi) may modulate the risk and severity of MI. We compared the risk and severity of MI in patients treated with TNFi with that in those receiving synthetic disease-modifying antirheumatic drugs (sDMARDs). Methods This analysis included patients with RA recruited from 2001 to 2009 to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis starting TNFi (etanercept/infliximab/adalimumab) and a biologic-naïve comparator cohort receiving sDMARD. All patients were followed via physician and patient questionnaires and national death register linkage. Additionally, all patients were linked to the Myocardial Ischaemia National Audit Project, a national registry of hospitalisations for MI. Patients were censored at first verified MI, death, 90 days following TNFi discontinuation, last physician follow-up or 20 April 2010, whichever came first. The risk of first MI was compared between cohorts using COX regression, adjusted with propensity score deciles (PD). MI phenotype and severity were compared using descriptive statistics. 6-month mortality post MI was compared using logistic regression. Results 252 verified first MIs were analysed: 58 in 3058 patients receiving sDMARD and 194 in 11 200 patients receiving TNFi (median follow-up per person 3.5 years and 5.3 years, respectively). The PD-adjusted HR of MI in TNFi referent to sDMARD was 0.61 (95% CI 0.41 to 0.89). No statistically significant differences in MI severity or mortality were observed between treatment groups. Conclusions Patients with RA receiving TNFi had a decreased risk of MI compared with patients with RA receiving sDMARD therapy over the medium term. This might be attributed to a direct action of TNFi on the atherosclerotic process or better overall disease control. © 2017 BMJ Publishing Group Ltd & European League Against Rheumatism.


Dixon W.G.,University of Manchester | Watson K.D.,University of Manchester | Lunt M.,University of Manchester | Mercer L.K.,University of Manchester | And 29 more authors.
Arthritis Care and Research | Year: 2010

Objective. 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. Methods. 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. Results. 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. Conclusion. 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. © 2010, American College of Rheumatology.


Lodi S.,University College London | Lodi S.,Institute Salud Carlos III | Phillips A.,University College London | Fidler S.,Imperial College London | And 137 more authors.
PLoS ONE | Year: 2013

Background:The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation.Methods:Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion).Results:Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm3 and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively.Conclusion:Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance. © 2013 Lodi et al.


Mercer L.K.,University of Manchester | Green A.C.,University of Manchester | Green A.C.,Queensland Institute of Medical Research | Galloway J.B.,University of Manchester | And 36 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objectives: To compare the risk of keratinoctye skin cancer (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) in patients treated for rheumatoid arthritis (RA) compared with the general population, and to determine whether anti-tumour necrosis factor (TNF) therapy exacerbates this risk. Methods: Patients with RA enrolled in the British Society for Rheumatology Biologics Register, a prospective national cohort established in 2001 to monitor the safety of anti-TNF, were followed until 2008. 11 881 patients treated with anti-TNF were compared with 3629 patients receiving non-biological disease-modifying antirheumatic drugs (nbDMARD). Standardised incidence ratios (SIR) were calculated for each cohort and rates between cohorts were compared using Cox proportional HR, adjusted using inverse probability of treatment weighting. Results: SIR for skin cancer was increased in both cohorts compared with the English population: SIR 1.72 (95% CI 1.43 to 2.04) anti-TNF; 1.83 (95% CI 1.30 to 2.50) nbDMARD only. In patients without previous skin cancer, BCC incidence per 100 000 patient-years was 342 (95% CI 290 to 402) after anti-TNF and 407 (95% CI 288 to 558) after nbDMARD. HR after anti-TNF adjusted for treatment weighting was 0.95 (95% CI 0.53 to 1.71). SCC incidence per 100 000 patient-years: anti-TNF 53 (95% CI 33 to 79); nbDMARD 43 (95% CI 12 to 110); adjusted HR 1.16 (95% CI 0.35 to 3.84). Conclusions: Skin cancers were increased among treated patients with RA. No evidence was found that anti-TNF therapy exacerbates the risk of BCC or SCC but this cannot be excluded. Patients with RA should use sun protection and be monitored for skin cancer.


Mercer L.K.,University of Manchester | Lunt M.,University of Manchester | Low A.L.S.,University of Manchester | Dixon W.G.,University of Manchester | And 32 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Background Patients with rheumatoid arthritis (RA) have an increased risk of certain solid cancers, in particular lung cancer, compared to the general population. Treatment with tumour necrosis factor (TNF) inhibitors (TNFi) may further enhance this risk. Objectives To compare the risk of solid cancer in patients with RA treated with TNFi to that in patients treated with non-biologic (synthetic) disease modifying antirheumatic drugs (sDMARDs). Methods Patients with a physician diagnosis of RA enrolled in the British Society for Rheumatology Biologics Register, a national prospective cohort study established in 2001 to monitor the long-term safety of TNFi, were followed via record linkage with the national cancer registries until first solid cancer, death, for 5 years, or until 2011. Rates of solid cancers in 11 767 patients without prior cancer who received TNFi were compared to those in 3249 patients without prior cancer treated with sDMARDs. Results 427 solid cancers were reported in 52 549 patient-years follow-up for the TNFi group (81 (95% CI 74 to 89) per 10 000 patient-years) and 136 cancers were reported in 11 672 patient-years in the sDMARD cohort (117 (95% CI 98 to 138) per 10 000 patient-years). After adjusting for differences in baseline characteristics there was no difference in risk of solid cancer for TNFi compared to sDMARD treated patients: HR 0.83 (95% CI 0.64 to 1.07). There was no difference in the relative risk of cancer for any of the individual TNFi drugs. Conclusions The addition of TNFi to sDMARD does not alter the risk of cancer in RA patients selected for TNFi in the UK. © 2014 BMJ Publishing Group Ltd & European League Against Rheumatism.


Mercer L.K.,University of Manchester | Lunt M.,University of Manchester | Low A.L.S.,University of Manchester | Dixon W.G.,University of Manchester | And 32 more authors.
Annals of the Rheumatic Diseases | Year: 2015

Background Patients with rheumatoid arthritis (RA) have an increased risk of certain solid cancers, in particular lung cancer, compared to the general population. Treatment with tumour necrosis factor (TNF) inhibitors (TNFi) may further enhance this risk. Objectives To compare the risk of solid cancer in patients with RA treated with TNFi to that in patients treated with non-biologic (synthetic) disease modifying antirheumatic drugs (sDMARDs). Methods Patients with a physician diagnosis of RA enrolled in the British Society for Rheumatology Biologics Register, a national prospective cohort study established in 2001 to monitor the long-term safety of TNFi, were followed via record linkage with the national cancer registries until first solid cancer, death, for 5 years, or until 2011. Rates of solid cancers in 11 767 patients without prior cancer who received TNFi were compared to those in 3249 patients without prior cancer treated with sDMARDs. Results 427 solid cancers were reported in 52 549 patient-years follow-up for the TNFi group (81 (95% CI 74 to 89) per 10 000 patient-years) and 136 cancers were reported in 11 672 patient-years in the sDMARD cohort (117 (95% CI 98 to 138) per 10 000 patientyears). After adjusting for differences in baseline characteristics there was no difference in risk of solid cancer for TNFi compared to sDMARD treated patients: HR 0.83 (95% CI 0.64 to 1.07). There was no difference in the relative risk of cancer for any of the individual TNFi drugs. Conclusions The addition of TNFi to sDMARD does not alter the risk of cancer in RA patients selected for TNFi in the UK.

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