Rebecca Davies

Risk of cancer in patients receiving non-biologic disease-modifying therapy for rheumatoid arthritis compared with the UK general population

Objectives. To quantify the risk of cancer and compare it with that for the general population in a modern cohort of UK patients with RA and to identify risk factors for cancer among this cohort. Methods. The study population comprised biologic-naïve RA subjects receiving non-biologic disease-modifying therapy recruited to the British Society for Rheumatology Biologics Register from 2002 to 2009. Standardized incidence ratios (SIRs) for cancers were calculated using age- and gender-specific cancer rates in the English population. Poisson regression models adjusted for age and gender using England general population data were used to determine the association of other predictors with incident malignancy. Results. The cohort comprised 3771 individuals with RA contributing 13 315 person-years of follow-up. One hundred and eighty-two cancers were reported: 156 solid and 26 myelo- or lymphoproliferative cancers. The overall SIR was 1.28 (95% CI 1.10, 1.48). Risks of lung cancer (SIR 2.39, 95% CI 1.75, 3.19), Hodgkin lymphoma (SIR 12.82, 95% CI 4.16, 29.92) and non-Hodgkin lymphoma (SIR 3.12, 95% CI 1.79, 5.07) were higher compared with the general population and risks of prostate cancer (SIR 0.35, 95% CI 0.11, 0.82) and cancers of the female genital organs (SIR 0.35, 95% CI 0.10, 0.90) were reduced. Within the cohort, cancer risk was more than 2-fold higher in current or ex-smokers than in non-smokers. Conclusion. The overall incidence of cancer was increased in this national cohort of subjects with RA. The association of RA with certain cancers needs to be considered when studying the effects of biologic therapy, such as anti-TNF, on cancer risk.

The influence of anti-TNF therapy upon incidence of keratinocyte skin cancer in patients with rheumatoid arthritis: longitudinal results from the British Society for Rheumatology Biologics Register

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.

Venous thrombotic events are not increased in patients with rheumatoid arthritis treated with anti‑TNF therapy: results from the British Society for Rheumatology Biologics Register

Objectives Past studies have reported conflicting rates of venous thrombotic events (VTEs) in rheumatoid arthritis (RA). The current study aimed to compare (1) the rates of VTEs in patients with RA treated with anti-tumour necrosis factor (anti-TNF) therapy versus those treated with non-biological disease-modifying antirheumatic drugs (nbDMARDs) alone and (2) the rates between each individual anti-TNF agent and nbDMARDs. Methods Using data from the British Society for Rheumatology Biologics Register, a national prospective observational cohort study of biological safety in patients with RA, the authors compared the incidence of VTEs between 11 881 anti-TNF- and 3673 nbDMARD-treated patients. Analysis was limited to the first VTE per person. HRs were calculated using Cox modelling. Adjustment was made for potential confounders including surgery performed during follow-up. Results A total of 196 first VTEs were reported (151 anti-TNF, 45 nbDMARD). Overall there was no difference in the rates of VTEs between anti-TNF- and nbDMARD-treated patients (adjusted HR 0.8 (95% CI 0.5 to 1.5)). The risk was similar across all anti-TNF agents. Rates of postoperative VTEs did not significantly differ between groups. Conclusions These data suggest that anti-TNF therapy is not associated with an increased risk of VTEs in RA patients.

Exploring the role of characteristic motion when learning new faces

Previous research has shown that it is easier to recognize familiar faces when shown moving, rather than static, especially when viewing conditions are difficult (Knight & Johnston, 1997; Lander, Christie, & Bruce, 1999). One possible theoretical reason for the moving-face advantage is that we learn “characteristic motion signatures” for familiar faces, associated with the face representation in memory. To examine this idea we investigated the role of motion at test when learning faces from either static images or moving sequences (Experiment 1). Results suggest that there is only an advantage for motion at test when the face is learned moving. In Experiment 2 we map the importance of facial motion as a face becomes increasingly familiar, on a television drama. We demonstrate that the beneficial effect of motion is not dependent on the amount of time the face is viewed. Results from both experiments support the idea of rapidly learned characteristic motion patterns.

Health Assessment Questionnaire disability progression in early rheumatoid arthritis: Systematic review and analysis of two inception cohorts

Objective The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. Methods Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. Results The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. Conclusion Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit.

Influence of anti-TNF patient warning regarding avoidance of high risk foods on rates of listeria and salmonella infections in the UK

Tumour necrosis factor (TNF) plays a pivotal role in the control of bacterial intracellular infection.1 The introduction of anti-TNF therapy to treat rheumatoid arthritis (RA) prompted the investigation of infection rates within these patients.2 Following an early signal of an increased risk of tuberculosis in anti-TNF treated patients,3 there have been many reports suggesting an increased risk of other intracellular bacterial infections, including listeria and salmonella.4 ,5 Indeed, the BSR Biologics Register (BSRBR) has reported an increase of such infections within anti-TNF treated patients compared with patients treated with non-biologic disease-modifying antirheumatic drugs.6 In response to these findings, patient information leaflets for anti-TNF agents (etanercept (ETN), infliximab (INF), adalimumab (ADA)) were modified in the UK in January 2006 advising patients to avoid high risk foods, such as raw eggs and poultry, which are associated with an increased risk of these infections.7–9 Given the addition of this advice, we investigated the rate of bacterial intracellular infection, before and after these guidelines were introduced, in RA patients treated with anti-TNF therapy within the BSRBR.10 A total of 11 723 patients with RA starting their first anti-TNF on enrolment in the BSRBR were included. This comprised 9376 patients starting therapy …

Medically Significant Infections Are Increased in Patients With Juvenile Idiopathic Arthritis Treated With Etanercept: Results From the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study.

The association between anti–tumor necrosis factor therapy and increased rates of infection is widely documented in adults with rheumatoid arthritis. Findings in children with juvenile idiopathic arthritis (JIA) have been less well documented. The aims of this analysis were to compare the rates of medically significant infections (MSIs) in children with JIA treated with etanercept (ETN) versus methotrexate (MTX) and to compare the rates between combination therapy with ETN plus MTX and monotherapy with ETN.

Factors associated with choice of biologic among children with Juvenile Idiopathic Arthritis: results from two UK paediatric biologic registers

Objective. The objectives of this study were to describe patients starting first-line biologics for JIA, to describe characteristics over time among patients starting etanercept, and to describe patterns of second biologic prescribing. Methods. The British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study, and the Biologics for Children with Rheumatic Diseases study are ongoing prospective observational cohorts, collecting data on patients starting biologic therapy for JIA. Patients registered from 1 January 2010 starting their first biologic were compared between therapies. Patients starting etanercept before 2010 were included to analyse changes in etanercept prescribing. The pathway of patients starting a second biologic was recorded in all patients. Results. To 26 August 2014, 931 patients were recruited starting a first-line biologic (142 Biologics for Children with Rheumatic Diseases; 789 British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study). From 2010, patients with systemic JIA (sJIA) were almost exclusively prescribed anakinra or tocilizumab. Choice between anti-TNF therapies was largely driven by history of chronic anterior uveitis (CAU). When investigating trends in patients starting etanercept over time, disease duration at etanercept start, patients with sJIA, a history of CAU, and those who received concomitant oral corticosteroids decreased over time. Patients who started a second biologic from 1 January 2010 showed a similar stratification. Conclusion. Although etanercept remains the most common biologic prescribed for JIA, there has been a clear shift towards the use of alternative biologics, largely driven by disease subtype and history of CAU. This channelling of children towards specific therapies should be considered carefully in future studies and in clinical guidelines and ongoing research.

Detection and evaluation of a drug safety signal concerning pancreatic cancer: lessons from a joint approach of three European biologics registers

OBJECTIVES A high incidence of pancreatic cancer (PCa) in patients exposed to was observed in the German biologics register. To evaluate this possible safety signal, a concerted analysis with the national biologics registers in the UK and Sweden was performed. METHODS Patients with enrolled in the British Society of Rheumatology Biologics Register (BSRBR), the Swedish Rheumatology Register (SRR) or the German Biologics Register [Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT)] were analysed. The patients were exposed to biologic or conventional DMARDs. Outcomes were obtained from physician reports, health authorities and via linkage to national cancer and death registers. Age- and gender-standardized incidence ratios (SIRs) of PCa were calculated based on the expected rates available from the individual national cancer registers. RESULTS Data from 5126 (Germany), 16 930 (UK) and 19 351 (Sweden) RA patients were available for the analysis. The highly discrepant prescription rates of LEF in the respective countries resulted in 11 343 (Germany), 30 787 (UK) and 2518 (S) patient-years of exposure to LEF. Compared with the general population, the incidence of PCa in patients ever exposed to LEF corresponded to a SIR of 3.1 (95% CI 1.3, 6.5) in Germany, 1.05 (95% CI 0.5, 2.1) in the UK and 1.8 (95% CI 0.1, 10.2) in Sweden. CONCLUSION The results of the replication analyses do not support the hypothesis of an increased risk of PCa in patients exposed to treatment with LEF. However, they do not completely rule out concerns, and therefore further verification in other data sets is recommended.

Does face familiarity influence speechreadability

The impact of face familiarity on the speechreadability of faces is examined. First we measured the baseline speechreading performance of participants, from unfamiliar faces. Next, participants were familiarized with the face and voice of either the same or a different speaker, or were asked to take part in a word puzzle instead. Speechreading performance was measured again, before participants completed a further period of familiarization (or puzzle completion) and a final speechreading performance task. Results showed that speechreading performance increased overall with practice but that performance increased significantly more as participants became increasingly familiar with the same speaker. Our findings demonstrate the importance of talker-specific variations or other instance-based characteristics and suggest that these are a useful source of information for speechreading.