Chris Deighton

BSR and BHPR rheumatoid arthritis guidelines on safety of anti-TNF therapies.

Inhibitors of TNF-a represent important treatment advances for a number of inflammatory conditions, including RA. TNF-a inhibitors offer a targeted strategy that contrasts with the non-specific immunosuppressive agents traditionally used to treat most forms of systemic inflammation. Information on who benefits from these agents and on their adverse effects continues to be collected through clinical studies, case series and reports and through national registries. In 2001 and 2005, the British Society for Rheumatology (BSR) established and updated guidelines for the use of anti-TNF drugs in RA [1, 2]. These guidelines have indicated which adult patients with RA should be eligible for treatment with anti-TNF therapies, precautions that need to be taken in their use and action that should be taken in the event of adverse effects. The previous guidelines applied to the then-available anti-TNF therapies {etanercept and infliximab in 2001 [1], and etanercept, infliximab and adalimumab (first-generation anti-TNF agents) in 2005 [2]}. Due to the large volume of information now available on these agents the BSR has, in 2010, produced separate guidelines on eligibility for anti-TNF treatment in RA (in press) These current guidelines cover the safety aspects of anti-TNF treatment in RA and apply to the first-generation products but also to the newly licensed second-generation anti-TNF drugs, certolizumab pegol and golimumab. There are relatively little safety data specifically for these second-generation agents but there are no data thus far to suggest that their side-effect profile would differ significantly from the first-generation agents. This is a rapidly changing field with new data emerging each month, so it is vital that clinicians keep up to date with this area of practice. These guidelines have Rheumatology Department, Royal Derby Hospital, Derby, Rheumatology Unit, Queen Alexandra Hospital, Portsmouth, Rheumatology Department, Nuffield Orthopaedic Centre, Oxford, Rheumatology Department, Poole Hospital, Poole, ARC Epidemiology Unit, University of Manchester, Manchester, Rheumatology Department, St George’s Healthcare, London, Rheumatology Department, Royal Lancaster Infirmary, Lancaster, Rheumatology Department, St Helens Hospital, St Helens, National Rheumatoid Arthritis Society, Maidenhead, Rheumatology Department, Addenbrooke’s Hospital, Cambridge, Rheumatology Department, Trafford General Hospital, Manchester, Rheumatology Unit, Worthing and Southlands NHS Trust, Worthing and Rheumatology Department, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK.

Management of rheumatoid arthritis: summary of NICE guidance

Rheumatoid arthritis is a chronic, progressive autoimmune disease associated with inflammation principally in synovial joints and affecting over 400 000 people in the United Kingdom.1 In recent years it has become clear that pain and disability can be avoided if the disease is recognised early and treated promptly and appropriately. It is therefore crucial that all health professionals have knowledge of the recognition, management, and appropriate referral of patients with rheumatoid arthritis. This article summarises the recommendations in the guideline from the National Institute for Health and Clinical Excellence (NICE) on the management of rheumatoid arthritis, from early identification to managing chronic and severe disease.2 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, recommendations are based on the opinion of the Guideline Development Group (GDG) of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Referral, diagnosis, and investigations [ Based on high and moderate quality observational studies of early prognosis and identification or diagnosis ] [ Based on data from case series ]

BSR and BHPR rheumatoid arthritis guidelines on eligibility criteria for the first biological therapy.

Chris Deighton1, Kimme Hyrich2, Tina Ding1, Jo Ledingham3, Mark Lunt2, Raashid Luqmani4, Patrick Kiely5, Marwan Bukhari6, Rikki Abernethy7, Andrew Ostor8, Ailsa Bosworth9, Kate Gadsby1, Frank McKenna10, Diana Finney11 and Josh Dixey12, on behalf of BSR Clinical Affairs Committee & Standards, Audit and Guidelines Working Group and the BHPR 1Rheumatology Department, Royal Derby Hospital, Derby; 2ARC Epidemiology Unit, University of Manchester, Manchester; 3Rheumatology Unit, Queen Alexandra Hospital, Portsmouth; 4Rheumatology Department, Nuffi eld Orthopaedic Centre, Oxford; 5Rheumatology Department, St George’s Healthcare, London; 6Rheumatology Department, Royal Lancaster Infi rmary, Lancaster; 7Rheumatology Department, St Helens Hospital, St Helens; 8Rheumatology Department, Addenbrooke’s Hospital, Cambridge; 9National Rheumatoid Arthritis Society, Maidenhead; 10Department of Rheumatology, Trafford General Hospital, Manchester; 11Rheumatology Unit, Worthing and Southlands NHS Trust, Worthing; 12Department of Rheumatology, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK

Neutropenia in patients receiving anti–tumor necrosis factor therapy

To examine the rates of and risk factors for neutropenia together with the dynamics of neutrophil and other white cell subset counts in a cohort of patients treated with a tumor necrosis factor (TNF) inhibitor for inflammatory arthritis.

Benefit of anti-TNF therapy in rheumatoid arthritis patients with moderate disease activity

Objectives. Anti-TNF therapy has improved outcomes for patients with highly active RA. Less is known about its effectiveness in patients with lower disease activity. The aim of this analysis is to compare the response to anti-TNF therapy between RA patients with high (DAS28 > 5.1) and moderate (DAS28 > 3.2–5.1) disease activity. Methods. A total of 4687 anti-TNF and 344 DMARD patients with high disease activity despite treatment with two standard DMARDs (including MTX) and 224 anti-TNF- and 300 DMARD-treated patients with moderate disease activity were selected from the British Society For Rheumatology Biologics Register. Mean change in HAQ over the first 12 months of enrolment was compared first between anti-TNF-treated and untreated patients in each DAS28 group, and then between anti-TNF-treated patients in the moderate and high DAS28 groups, using doubly robust estimates, adjusting for age, gender, disease duration, baseline HAQ and DAS28 score, number of previous DMARDs and steroid use. Results. Compared with anti-TNF-untreated patients within each DAS group, treated patients were younger, had higher DAS28 and HAQ and had failed a higher number of previous DMARDs. The mean adjusted change in HAQ over 12 months was similar in anti-TNF-treated patients with moderate and high disease activity at baseline: moderate −0.26 (95% CI −0.35, −0.16), high −0.28 (95% CI −0.34, −0.23) and mean difference −0.03 (95% CI −0.14, 0.08). Conclusions. Improvement in HAQ score 12 months after start of anti-TNF therapy was not dependent on baseline DAS28 scores, suggesting that substantial benefits may also be gained by treating those with moderately active disease despite standard DMARD therapy.

BSR and BHPR guidelines on the use of rituximab in rheumatoid arthritis

The Standards, Audit and Guidelines Working Group (SAGWG) of the British Society for Rheumatology (BSR) have recently updated the guidelines on eligibility for anti-TNF drugs in RA [1] and have updated the anti-TNF safety and efficacy guidelines [2] for general use of the rheumatology community. The National Institute for Heath and Clinical Excellence (NICE) in the UK, which is the is an independent organization responsible for providing national guidance in the UK on promoting good health and preventing and treating ill health, has published a technology appraisal guidance [3] for use of rituximab in RA in 2007. Furthermore, a consensus statement from EULAR [4] was also published in 2007. Therefore, it was felt appropriate to undertake a review of the currently available data as new evidence was available. The group did not wish to duplicate the guidance in those documents, but wished to review the more recent evidence and supplement what is already known.

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.

Evidence for genetic anticipation in nodal osteoarthritis

OBJECTIVE Evidence was sought for genetic anticipation (disease occurring at an earlier age in subsequent generations, with increasing severity) in nodal osteoarthritis (NOA). METHODS Age at symptom onset and disease severity was compared within 30 parent/offspring pairs with NOA. Correlation between the offspring age of disease onset and the parental age at conception was also assessed. RESULTS The age at onset of nodal symptoms was earlier in the offspring (43 years (95% confidence intervals (CI) 38 to 47) v 61 (CI 58 to 65); mean difference 18 years (CI 13 to 22): p< 0.001) as was large joint symptom onset (48 years (CI 41 to 55) v 67 (CI 61 to 73); mean difference 20 years (CI 13 to 27): p< 0.01). A negative correlation existed between age of offspring symptom onset and parental age at conception. Fifteen (50%) offspring had similar or more extensive disease than their parents. CONCLUSIONS These results suggest genetic anticipation occurs in NOA and if confirmed a search for trinucleotide repeats is warranted.

Cost-Effectiveness of Combination Nonbiologic Disease-Modifying Antirheumatic Drug Strategies in Patients with Early Rheumatoid Arthritis

Objective. To compare the costs and benefits of alternative combination strategies of disease-modifying antirheumatic drugs (DMARD) and DMARD monotherapy in patients with early, active rheumatoid arthritis (RA). Methods. Data were drawn from randomized controlled trials that compared DMARD monotherapy or any DMARD combination strategy, with or without combined steroid therapy. Mixed treatment comparison methods were used to estimate the relative effectiveness of the different strategies. A mathematical model was developed to compare the longterm costs and benefits of the alternative strategies, combining data from a variety of sources. Costs were considered from a health sector viewpoint and benefits were expressed in terms of quality-adjusted life-years (QALY). Results. If decision makers use a threshold of £20,000 (US

Further evidence for genetic anticipation in familial rheumatoid arthritis.

29,000) per QALY, then the strategies most likely to be cost-effective are either DMARD combination therapy with downward titration (probability of being optimal = 0.50) or intensive, triple DMARD combination therapy (probability of being optimal = 0.43). The intensive DMARD strategy generated an additional cost of £27,392 per additional QALY gained compared to the downward titration strategy. Other combination strategies were unlikely to be considered cost-effective compared to DMARD monotherapy. Results were robust to a range of scenario sensitivity analyses. Conclusion. Combination DMARD therapy is likely to be cost-effective compared to DMARD monotherapy where treatment entails rapid downward dose titration or intensive, triple DMARD therapy.