Disease activity and cognition in rheumatoid arthritis : an open label pilot study

Acknowledgements This work was supported in part by NIHR Newcastle Biomedical Research Centre. Funding for this study was provided by Abbott Laboratories. Abbott Laboratories were not involved in study design; in the collection, analysis and interpretation of data; or in the writing of the report.Peer reviewedPublisher PD

Patient and researcher perspectives on facilitating patient and public involvement in rheumatology research

No abstract available

Antibody engineering to develop new antirheumatic therapies

There has been a therapeutic revolution in rheumatology over the past 15 years, characterised by a move away from oral immuno-suppressive drugs toward parenteral targeted biological therapies. The potency and relative safety of the newer agents has facilitated a more aggressive approach to treatment, with many more patients achieving disease remission. There is even a prevailing sense that disease 'cure' may be a realistic goal in the future. These developments were underpinned by an earlier revolution in molecular biology and protein engineering as well as key advances in our understanding of rheumatoid arthritis pathogenesis. This review will focus on antibody engineering as the key driver behind our current and developing range of antirheumatic treatments

Analysis of Fcγ receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B

The Fcγ receptors play important roles in the initiation and regulation of many immunological and inflammatory processes, and genetic variants (FCGR) have been associated with numerous autoimmune and infectious diseases. The data in rheumatoid arthritis (RA) are conflicting and we previously demonstrated an association between FCGR3A and RA. In view of the close molecular proximity with FCGR2A, FCGR2B and FCGR3B, additional polymorphisms within these genes and FCGR haplotypes were examined to refine the extent of association with RA. Biallelic polymorphisms in FCGR2A, FCGR2B and FCGR3B were examined for association with RA in two well characterized UK Caucasian and North Indian/Pakistani cohorts, in which FCGR3A genotyping had previously been undertaken. Haplotype frequencies and linkage disequilibrium were estimated across the FCGR locus and a model-free analysis was performed to determine association with RA. This was followed by regression analysis, allowing for phase uncertainty, to identify the particular haplotype(s) that influences disease risk. Our results reveal that FCGR2A, FCGR2B and FCGR3B were not associated with RA. The haplotype with the strongest association with RA susceptibility was the FCGR3A–FCGR3B 158V-NA2 haplotype (odds ratio 3.18, 95% confidence interval 1.13–8.92 [P = 0.03] for homozygotes compared with all genotypes). The association was stronger in the presence of nodules (odds ratio 5.03, 95% confidence interval 1.44–17.56; P = 0.01). This haplotype was also more common in North Indian/Pakistani RA patients than in control individuals, but not significantly so. Logistic regression analyses suggested that FCGR3A remained the most significant gene at this locus. The increased association with an FCGR3A–FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis

Drug breakthrough offers hope to arthritis sufferers: qualitative analysis of medical research in UK newspapers

BackgroundNewspaper stories can impact behaviours, particularly in relation to research participation. It is therefore important to understand the narratives presented and ways in which these are received. Some work to date assumes journalism transmits existing medical knowledge to a passive audience. This study aimed to explore how newspaper articles present stories about medical research and how people interpret and use them.DesignQualitative research methods were employed to analyse two data sets: newspaper articles relating to ‘rheumatoid arthritis’ and ‘research’ from UK local and national news sources; and existing transcripts of interviews with patients with rheumatoid arthritis and their carers.ResultsNewspapers present a positive account of medical research, through a simple narrative with three essential components: an ‘innovation’ offers ‘hope’ in the context of ‘burden’. Patients frequently feature as passive subjects without attributed opinions. Few articles include patients’ experiences of research involvement. Patients with rheumatoid arthritis and their carers read articles about medical research critically, often with cynicism and drawing on other sources for interpretation.ConclusionsAn understanding of the simple, positive narrative of medical research found in newspaper articles may enable researchers to gain mass media exposure for their work and challenge this typical style of reporting. The critical and cynical ways patients and carers read stories about medical research suggest that concerns about newspaper articles misinforming the public may be overstated, but any effect on research engagement is unknown. Newspaper articles rarely present patients’ views or their experiences of research, and this can be conceptualized as ‘depersonalization bias’

Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106871/1/pros22818.pd

High frequency of antidrug antibodies and association of random drug levels with efficacy in certolizumab pegol-treated patients with rheumatoid arthritis: results from the BRAGGSS cohort

Objectives: To evaluate (i) the association between random certolizumab drug levels, antidrug antibodies (ADAbs) and treatment response in patients with rheumatoid arthritis (RA); (ii) longitudinal factors associated with ADAbs and certolizumab drug levels. Methods: This prospective cohort included 115 patients with RA treated with certolizumab. Serum samples were collected at 3, 6 and 12 months following treatment initiation. Drug levels and ADAbs were measured using ELISA and radioimmunoassay, respectively, at 3, 6 and 12 months. Disease Activity Score in 28 joints (DAS28) were measured at each visit and 12 months European League Against Rheumatism (EULAR) response was calculated. Patient self-reported adherence was collected longitudinally. Ordinal logistic regression and generalised estimating equation were used to test the association: (i) between drug levels, from serum sampled and treatment response; (ii) between ADAbs and drug levels; (iii) patient-centred factors and drug levels. Results: ADAbs were detected in 37% (42/112 patients by 12 months). The presence of ADAbs were significantly associated with lower drug levels over 12 months (β=−0.037, 95% CI −0.055 to 0.018, p<0.0001) but not independently with 12 months EULAR response (β=0.0013 (95% CI −0.0032 to 0.00061), p=0.18). Drug level was associated with 12 months EULAR response (β=0.032 (95% CI 0.0011 to 0.063), p=0.042). In the multivariate model, ADAb level and adherence were significantly associated with drug concentrations. Conclusions: This is the first study to demonstrate that higher certolizumab drug levels are associated with better 12 months EULAR response. ADAbs in certolizumab-treated patients with RA were detected at higher levels than previous studies and help determine the aetiology of a low drug level