Rheumatoid Arthritis: Deighton C

Deighton C, O'Mahony R, Tosh J, Turner C, Rudolf M, Anonymous00075. · Department of Rheumatology, Derbyshire Royal Infirmary, Derby DE1 2QY. · BMJ. · Pubmed #19289413 No free full text.

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Ledingham J, Deighton C, Anonymous00040. · Queen Alexandra Hospital, Portsmouth, UK. · Rheumatology (Oxford). · Pubmed #15637039 links to  free full text

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Deighton C, Hyrich K. · No affiliation provided · Rheumatology (Oxford). · Pubmed #18784124 No free full text.

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Bukhari M, Bamji AN, Deighton C. · No affiliation provided · Rheumatology (Oxford). · Pubmed #17956915 No free full text.

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Deighton C, Criswell LA. · Rosalind Russell Medical Research Center for Arthritis, University of California-San Francisco, 374 Parnassus Avenue, Box 0500, San Francisco, CA 94143-0500, USA. · Curr Rheumatol Rep. · Pubmed #16973114 No free full text.

Abstract: Recent progress in defining the role of genetic factors in rheumatoid arthritis (RA) has been remarkable. Anticyclic citrullinated peptide (anti-CCP) antibody-positive disease appears to be immunogenetically distinct from anti-CCP-negative disease, with the former subgroup primarily responsible for association and linkage with the HLA-DRB1 shared epitope (SE). There is preliminary evidence that non-HLA genes contribute differentially to anti-CCP-positive and negative disease. The phenotypic differences evident in anti-CCP-positive and negative disease suggest a need to reclassify RA based on the presence or absence of this autoantibody. Some recent work also suggests marked interactions between cigarette smoking, anti-CCP antibodies, and the SE, though these relationships may vary across populations. Lastly, a recent single nucleotide polymorphism-based genome-wide linkage analysis of multicase RA families revealed novel genomic regions that likely contain genes that predispose to RA or more specific phenotypes.

Kalden JR, Schattenkirchner M, Sörensen H, Emery P, Deighton C, Rozman B, Breedveld F. · Department of Internal Medicine III, University of Erlangen-Nuremberg, Erlangen, Germany. · Arthritis Rheum. · Pubmed #12794818 links to  free full text

Abstract: OBJECTIVE: To investigate the efficacy and safety of leflunomide beyond 2 years in a multinational, open-label extension of 2 phase III double-blind studies. METHODS: Patients with rheumatoid arthritis (RA) who received leflunomide (100 mg/day for 3 days, 10 mg/day or 20 mg/day thereafter) in the 2 phase III studies and who completed 2 years of treatment were offered inclusion in the open-label extension phase and were maintained on the same dosage of leflunomide. The American College of Rheumatology revised criteria for 20% improvement (ACR20), ACR50, and ACR70 response rates, the Stanford Health Assessment Questionnaire (HAQ) scores, and C-reactive protein (CRP) levels were assessed. Safety measures included monitoring of adverse events and laboratory values. RESULTS: A total of 214 patients (mean age 57 years) were treated with leflunomide for >2 years; 74.8% of the patients were female. The mean disease duration was 4.1 years (range 0.1-26.6 years), and in 44% of patients, RA was first diagnosed within 2 years of entry into the phase III studies. The mean duration of leflunomide treatment was 4.6 years (range 2.8-5.8 years), and 32% of patients had received no previous treatment with disease-modifying antirheumatic drugs. ACR20, ACR50, and ACR70 response rates and HAQ scores at 1 year were maintained through year 4 or until the end point. No new types of adverse events were observed, and liver function was normal at baseline and at the end point in the majority of patients. CONCLUSION: The improvements in both functional ability and physician-based efficacy measures seen with leflunomide after 1 year were maintained for up to 5 years (maximum treatment duration 5.8 years), demonstrating that the early efficacy of leflunomide in patients with RA is sustained long-term, and that the long-term safety profile of leflunomide is no different from that observed in phase III trials.

Rajakulendran S, Gadsby K, Deighton C. · Department of Rheumatology, Derbyshire Royal Infirmary, Derby, UK. · Musculoskeletal Care. · Pubmed #18702106 No free full text.

Abstract: INTRODUCTION: The summary of product characteristics for leflunomide and methotrexate recommend avoiding alcohol. By contrast, the latest British Society for Rheumatology (BSR) guidelines suggest that alcohol should be 'well within national limits'. A postal survey was performed of rheumatoid arthritis (RA) patients to address their alcohol consumption, and assess whether this influenced any rise in alanine transaminase (ALT) levels while on leflunomide or methotrexate. METHODS: RA patients commenced on methotrexate or leflunomide within the preceding two years were identified using the departmental database. A total of 200 patients on methotrexate or leflunomide were sent questionnaires covering demographics, disease details, duration of disease-modifying anti-rheumatic drug (DMARD) use, previous medical and drug history, alcohol advice recalled, and alcohol consumption while on the drug. ALT levels at drug commencement and the highest level on the drug were recorded. RESULTS: Replies were received from 69.5% of methotrexate and 57.5% of leflunomide patients. 68.6% of patients recalled receiving alcohol advice. 55.8% of leflunomide patients did not drink alcohol prior to taking the DMARD, compared with 39.4% of methotrexate patients. 27.7% of leflunomide patients continued to drink alcohol compared with 64.3% on methotrexate. For both drugs, no patterns emerged to suggest that baseline or highest ALT levels were influenced by higher levels of alcohol consumption. DISCUSSION: No differences were found with either methotrexate or leflunomide for self-reported alcohol consumption influencing ALT levels. It is appropriate to give similar alcohol advice to patients beginning therapy with either methotrexate or leflunomide. This research has not found any evidence to contradict the relaxation of advice on alcohol consumption with methotrexate and leflunomide in the updated BSR guidelines.

Rajakulendran S, Deighton C. · Department of Rheumatology Derbyshire Royal Infirmary, London Road, Derby, UK. · Curr Drug Saf. · Pubmed #18690936 No free full text.

Abstract: Etanercept is an anti-TNF drug with marked efficacy in inflammatory arthritis. This review addresses dermatological side effects that have been encountered in our 85 patients on the drug for rheumatoid arthritis, and reviews other reported cutaneous adverse events. Injection site reactions are common and usually self-limiting. We and others have encountered patients with recall site reactions where the four rotated injection sites simultaneously develop a hypersensitivity reaction. In all cases, the rash has responded to antihistamines and the etanercept was thereby continued. Other injection site reactions include discoid lupus and cutaneous vasculitis that respond to cessation of treatment and appropriate therapy. Skin reactions more distant from the injection site are also reviewed, with erythema nodosum, widespread lupus rashes, infections and skin tumours summarised. A patient who developed a purpuric rash at the site of last injection with a drug induced worsening of thrombocytopaenia is described. Although the therapeutic advantages of etanercept outweigh the side effects, clinicians need to be aware of the adverse reactions of these drugs with their increasing use.

Deighton C, Hyrich K. · Derbyshire Royal Infirmary, Department of Rheumatology, Derby, UK. · Nat Clin Pract Rheumatol. · Pubmed #18665149 No free full text.

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Smith N, Ding T, Butt S, Gadsby K, Deighton C. · Department of Rheumatology, Derbyshire Royal Infirmary, London Road, Derby, DE1 2QY, UK. · Rheumatology (Oxford). · Pubmed #18603597 No free full text.

Abstract: OBJECTIVES: The NICE re-appraisal of anti-TNF requires demonstration of ongoing response, making the baseline 28-joint Disease Activity Score (DAS28) crucially important. A retrospective analysis of all RA patients on their first anti-TNF determined predictive factors for those classified as non-responders at 6 months according to current NICE guidelines. METHODS: The patients were divided into responders (DAS28 dropped by >1.2) and non-responders. These groups were compared for demographics, DAS28 at the two pre-assessments 1 month apart and at baseline. Exposure to intramuscular, oral and IA steroids in the 3 months period before the baseline DAS28 was recorded. RESULTS: At 6-month assessment in 256 patients, 82.8% were responders with no demographic differences between them and non-responders. Although the first pre-assessment score was not significantly different (6.8 vs 6.6), the second pre-assessment score (7.1 vs 6.7) and the baseline DAS (7.2 vs 6.3) were lower in the non-responders (P < 0.04 and P < 0.001, respectively). Comparing the differences in DAS28 from the first pre-assessment to baseline, the responders had increased by 0.4, and the non-responders had decreased by 0.4, (P < 0.001). If the first pre-assessment score had been taken as the baseline DAS28, then 9.4% of responders would be re-classified as non-responders, and 31.8% of non-responders would be re-classified as responders. The proportion of patients who had steroid treatment within the 3 months period before the baseline DAS28 did not differ significantly between the responders and non-responders (34% vs 41%, P = 0.38). CONCLUSION: Baseline DAS28 is critical in classifying responders at the 6-month assessment.

Jerram S, Butt S, Gadsby K, Deighton C. · Department of Rheumatology, Derbyshire Royal Infirmary, London Road, Derby, DEI 2QY, UK. · Rheumatology (Oxford). · Pubmed #18160419 No free full text.

Abstract: OBJECTIVES: A discrepancy exists between the National Institute for Health and Clinical Excellence (NICE) guidelines for continuation of TNF therapy in RA and EULAR response criteria. We performed a retrospective study of patients starting anti-TNF therapy to establish how many NICE non-responders would have met EULAR response criteria, and whether this may increase. METHOD: We calculated the percentage of NICE non-responders who would have met EULAR moderate response criteria. We then compared the mean decrease in disease activity score (DAS28) for patients with low and high baseline scores. We analysed trends for treating RA in Derby with anti-TNF to address whether we were treating less active disease over time. RESULTS: At 3 months (n = 271 patients), 7.7% of NICE non-responders would have met EULAR moderate response criteria. At 6 months (n = 240 patients) this was 23.7%. Patients starting with a higher DAS28 had a significantly greater absolute drop in score. The mean decrease between the 1st and 3rd tertiles of patients divided by baseline DAS28 was significant at 3 and 6 months (P < 0.001). Derby rheumatologists were treating less active RA over time. Comparing the mean DAS28 baseline between the 1st and 3rd tertiles of patients divided by anti-TNF commencement date was significant (P < 0.001). CONCLUSIONS: A significant minority of NICE non-responders would fall within the moderate EULAR response criteria. This is likely to increase in future due to the increasing tendency to initiate anti-TNF in patients with less active disease. Consequently, NICE guidelines should be brought in line with EULAR response criteria.

Smith N, Gadsby K, Butt S, Carruthers D, Deeming A, Ledingham J, Fletcher M, Mulherin D, Roskell S, Kay L, Nicholl K, Cooper R, Worsley A, Deighton C. · Department of Rheumatology, Derbyshire Royal Infirmary, London Road, Derby, England, UK DE1 2QY. · Rheumatology (Oxford). · Pubmed #17666440 No free full text.

Abstract: OBJECTIVES: National Institute for Health and Clinical Excellence (NICE) guidelines for anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA) state that two pre-assessments of Disease Activity Score (DAS28) should be performed a month apart. We performed a retrospective audit of data from six centres to determine the stability of DAS28 between assessments, and the proportion of patients still satisfying eligibility criteria at baseline. METHODS: All RA patients assessed for anti-TNF from six centres had their pre-assessment DAS28 (DAS-1) compared with their baseline DAS28 (DAS0) using paired t-tests, and a similar analysis for the components of the DAS28. Patients who were no longer eligible for anti-TNF at DAS0 were noted. RESULTS: Six hundred and seventy-nine RA patients showed no significant change in the DAS28, with a mean DAS-1 of 6.74 and DAS0 of 6.73. (P = 0.86). Of the patients, 97.2% fulfilled the UK eligibility criteria at DAS0. Comparison of the individual components of the DAS28 between the two pre-assessment dates showed that there was no significant difference between either the numbers of swollen joints or the erythrocyte sedimentation rate (ESR), but there was a significant increase in the numbers of tender joints of 1.41 (P < 0.001) and in the visual analogue scale (VAS) of 4.22 (P < 0.001). DISCUSSION: The overwhelming majority of patients who fulfil eligibility criteria for anti-TNF drugs 1 month prior to baseline also fulfil the criteria at baseline. There is no significant change in the DAS28 over the month waiting to go onto anti-TNF therapy. A single assessment of the DAS28 would suffice to enable patients to go on to anti-TNF treatment.

Sandhu RS, Treharne GJ, Douglas KM, Cassim K, Saratzis A, Piper H, Erb N, Jenkins D, Tavakoli M, Deighton C, Kitas GD. · Primary Care Musculoskeletal Research Centre, Keele University, UK. · Musculoskeletal Care. · Pubmed #17117445 No free full text.

Abstract: BACKGROUND: Anti-tumour necrosis factor (anti-TNF) therapy has been an important development for the treatment of rheumatoid arthritis (RA) but the impact of its delivery on hospital resources in still emerging.Aims: We audited the effect of starting anti-TNF on the use of other anti-rheumatic therapies and hospital resources in a routine secondary care setting. METHODS: A retrospective study of resource use before and after anti-TNF was conducted. Hospital records of 54 RA patients were studied and data taken from the time of commencing anti-TNF to 1 October 2004 and an equal time period prior to commencing anti-TNF. Identical data were collected for 54 controls not on anti-TNF. Relevant figures were extrapolated to per annum rates. Results were analysed using two-factor ANOVAs comparing the pre- versus post-anti-TNF period. Cases on intravenous (IV) versus subcutaneous (SC) anti-TNF were also compared in separate ANOVAs. RESULTS: Mean duration of anti-TNF therapy was 17.04 months (range 3.60-42.36). Mean pre- and 3-months post-anti-TNF Disease Activity Scores (DAS28) were 6.93 and 3.88, respectively. Cases were more likely than controls to be on oral prednisolone pre- and post-anti-TNF. Methylprednisolone requirement, number of disease-modifying anti-rheumatic drugs (DMARDs), telephone helpline contacts and duration as an inpatient reduced significantly post-anti-TNF. Day case admissions increased but outpatient appointments decreased only in cases on IV anti-TNF. CONCLUSIONS: In a pragmatic setting, anti-TNF therapy led to reduced need for steroid injections and other DMARDs, as well as reductions in use of several hospital resources. Wider replication of these findings will be important for planning delivery.

Deighton C. · Derbyshire Royal Infirmary, Derby. · Musculoskeletal Care. · Pubmed #17042001 No free full text.

Abstract: In 2001 the British Society for Rheumatology (BSR) published guidelines for prescribing TNF-alphablockers in adults with rheumatoid arthritis (RA). In an unusual move, the National Institute of Clinical Excellence (NICE) accepted the BSR guidelines and published them unchanged and included them in their own Technology Appraisal (National Institute of Clinical Excellence, 2002). The field of anti-TNF in RA is rapidly changing, and the BSR Standards, Guidelines and Audit Working Group decided in 2004 to update the guidelines. These were published in February 2005 (Ledingham and Deighton, 2005). This article summarizes the key changes, and attempts to justify them, using further data that has emerged since the updated guidelines were produced, and audit data from the Derby Rheumatology department.

Deighton C, Criswell LA, Lum RF, Silman A. · Department of Rheumatology, Derbyshire Royal Infirmary, Derby, DE1 2QY, UK. · Rheumatology (Oxford). · Pubmed #16754627 links to  free full text

Abstract: OBJECTIVES: Previous work has suggested that features of genetic anticipation might be present in familial rheumatoid arthritis (RA), but bias is difficult to exclude when looking at disease in two consecutive generations. We used data from the North American Rheumatoid Arthritis Consortium (NARAC) and the Arthritis Research Campaign National repository for RA multicase pedigrees to determine whether differences in age of onset within multicase sibships were supportive of genetic anticipation. METHOD: RA sibling pairs were identified from both data sets. The period of observation was defined as the time between the first sibling developing RA and the time that the sibship was ascertained for the study. A paired t-test for the difference in ages of RA onset within the pairs was calculated. Ages of conception of the parent were correlated with the age of RA onset. RESULTS: Information was available for 743 sibships in the NARAC data set and 396 sibships in the Arthritis Research Campaign (ARC) data set. In both data sets, the older siblings had an older age of onset than their younger siblings (39.3 vs 36.9 in the NARAC, and 43.8 vs 40.1 in the ARC data set, both P < 0.001). The two data sets were then stratified into tertiles by a period of observation. In both data sets, there was a progressive decline in the sibling age of onset differences. For the first tertile (shortest observation period), the older sibling had a significantly older age of onset than the younger. This difference decreased in the second tertile, and was not significant in the third tertile (longest observation period). There was no significant correlation between the age of RA onset and the maternal or paternal ages of conception in either data set. CONCLUSION: Features compatible with genetic anticipation in RA multicase sibships are subject to observational bias. This does not support a role for genetic anticipation in familial RA.

Neame R, Hammond A, Deighton C. · Department of Rheumatology, King's Mill Hospital, Nottinghamshire, United Kingdom. · Arthritis Rheum. · Pubmed #15818715 links to  free full text

Abstract: OBJECTIVE: To measure the need for information about rheumatoid arthritis (RA) and the level of desire for involvement in treatment decisions among patients with RA. To examine the relationship between these preferences and what factors (sociodemographic, disease, treatment, level of disability, and level of knowledge about RA) associate with these preferences. METHODS: Questionnaire surveys were mailed to a randomly selected group of 600 patients with RA. Need for information and desire for involvement in decision making were measured using a validated tool (the Autonomy Preference Index). RESULTS: The response rate was 57.3%. The need for information was very high. Information seeking preference scores (median 82.5, interquartile range 80.0-92.5) were significantly higher (P < 0.001) than decision making preference scores (mean +/- SD 56.4 +/- 13.6). Need for information and for decision making were both higher in women than men, and associations with these needs differed in men and women. However, younger age and greater knowledge of RA predicted greater need for decision making. There was no correlation between need for information and for involvement in treatment decisions for either sex (women: r(s) = 0.09, P = 0.19; men: r(s) = -0.06, P = 0.54). CONCLUSION: There was a high level of need for information among patients with RA. Desire for involvement in treatment decision making was significantly lower and did not correlate with need for information. Associations with these needs differed for men and women.

Wenham C, Gadsby K, Deighton C. · No affiliation provided · Rheumatology (Oxford). · Pubmed #18180249 No free full text.

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Rajakulendran S, Gadsby K, Allen D, O'Reilly S, Deighton C. · No affiliation provided · Ann Rheum Dis. · Pubmed #17105865 No free full text.

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Deighton C, Ledingham J. · No affiliation provided · Rheumatology (Oxford). · Pubmed #16769774 links to  free full text

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Rajakulendran S, Deighton C. · No affiliation provided · Rheumatology (Oxford). · Pubmed #15564639 links to  free full text

This publication has no abstract.