Rheumatoid Arthritis: Capell H

Dale J, Alcorn N, Capell H, Madhok R. · Ayr County Hospital, and Glasgow Royal Infirmary, Centre for Rheumatic Diseases, Castle Street, Glasgow, UK. · Nat Clin Pract Rheumatol. · Pubmed #17664952 No free full text.

Abstract: Early aggressive treatment of rheumatoid arthritis is associated with improved disease control, slower radiological progression and improved functional outcomes. Tumor necrosis factor blocking therapy is effective but there remain concerns about long-term risks. Combining disease-modifying antirheumatic drugs (DMARDs) is a widely used therapeutic alternative; however, there is uncertainty surrounding the most effective regimen. A popular combination is methotrexate plus sulfasalazine, but each of these DMARDs can also be used in combination with other DMARDs and in triple therapy regimens. However, wide variations in study size, design, steroid usage and approaches to combination therapy have made it difficult to form firm conclusions regarding their efficacy. Generally, combination therapy is well tolerated and associated with no significant increase in the rate of adverse events compared with monotherapy. Methotrexate-sulfasalazine, methotrexate-chloroquine, methotrexate-cyclosporin, methotrexate-leflunomide, methotrexate-intramuscular-gold and methotrexate-doxycycline are effective combination regimens. Triple DMARD therapy is better than various DMARD monotherapy and dual therapy regimens. Methotrexate and hydroxychloroquine may have synergistic anti-inflammatory properties. Clinical trial evidence to support the use of other methotrexate and sulfasalazine combinations is often weak or lacking. Further investigation is required to determine the most effective regimen and approach to combination therapy.

Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Inês LB, de Koning EJ, Buttgereit F, Cutolo M, Capell H, Rau R, Bijlsma JW. · Reumatologia, Hospitais da Universidade, 3000-075 Coimbra, Portugal. · Ann Rheum Dis. · Pubmed #16107513 links to  free full text

Abstract: Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.

Sattar N, McCarey DW, Capell H, McInnes IB. · Department of Pathological Biochemistry and Centre for Rheumatic Diseases, North Glasgow Hospitals University NHS Trust, Glasgow Royal Infirmary, Glasgow, Scotland, UK. · Circulation. · Pubmed #14676136 links to  free full text

Abstract: There is intense interest in mechanisms whereby low-grade inflammation could interact with conventional and novel vascular risk factors to promote the atheromatous lesion. Patients with rheumatoid arthritis (RA), who by definition manifest persistent high levels of inflammation, are at greater risk of developing cardiovascular disease. Mechanisms mediating this enhanced risk are ill defined. On the basis of available evidence, we argue here that the systemic inflammatory response in RA is critical to accelerated atherogenesis operating via accentuation of established and novel risk factor pathways. By implication, long-term suppression of the systemic inflammatory response in RA should be effective in reducing risk of coronary heart disease. Early epidemiological observational and clinical studies are commensurate with this hypothesis. By contrast, risk factor modulation with conventional agents, such as statins, may provide unpredictable clinical benefit in the context of uncontrolled systemic inflammatory parameters. Unraveling such complex relationships in which exaggerated inflammation-risk factor interactions are prevalent may elicit novel insights to effector mechanisms in vascular disease generally.

Capell H. · Centre for Rheumatic Disease, Royal Infirmary, Glasgow, Scotland. · J Rheumatol Suppl. · Pubmed #12435167 No free full text.

Abstract: Longterm safety and efficacy of disease modifying antirheumatic drugs (DMARD) have been challenging to assess. There are few studies that have evaluated patient outcome beyond 5 years. As patients may receive several DMARD over the course of their disease a long with nonsteroidal antiinflammatory drugs, corticosteroids, and other drugs for comorbidities, it is difficult to design and implement a trial to define a specific drug's longterm effect. Based on the findings of several key studies, however, it does appear that DMARD are safe when taken longterm, and that they are more likely to be discontinued because of inefficacy than toxicity. Although DMARD are often discontinued because of lack of efficacy, 12 year data suggest that DMARD can provide benefit over this period. The toxicity profiles vary significantly between DMARD. In addition, the time during therapy when the majority of these adverse effects most frequently appear is DMARD-specific. Prospective studies are needed to further clarify longterm safety and efficacy of the newer DMARD.

Hamilton J, Capell H. · Centre for Rheumatic Diseases, Royal Infirmary, Glasgow, UK. · Expert Opin Pharmacother. · Pubmed #11583059 No free full text.

Abstract: Until recently, two different classification systems for juvenile arthritis (JA) were utilised, each with its own terminology and subclassification. It has been recognised that particularly within the polyarticular and pauciarticular groups, many distinct subsets exist each with a different prognosis. As a result, a new classification system for JA has been developed. It is hoped that this will allow more accurate assessment of incidence and aetiology of the various subtypes in future generations and in time will allow therapy to be targeted at those most likely to achieve benefit. Since there is a new classification system for JA, the vast majority of published clinical studies were performed using the old classification system. For the purposes of this review, unless otherwise stated, the American College of Rheumatology classification will be used. This is outlined in Table 1 with clinical features of the major subtypes described in Table 3. This review will cover current best practice and discuss future directions for research using the recent advances in the treatment of rheumatoid arthritis (RA) as a model.

Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, Kincaid W, Porter D. · Gartnavel General Hospital, Glasgow G12 0YN, UK. · Lancet. · Pubmed #15262104 No free full text.

Abstract: BACKGROUND: Present treatment strategies for rheumatoid arthritis include use of disease-modifying antirheumatic drugs, but a minority of patients achieve a good response. We aimed to test the hypothesis that an improved outcome can be achieved by employing a strategy of intensive outpatient management of patients with rheumatoid arthritis--for sustained, tight control of disease activity--compared with routine outpatient care. METHODS: We designed a single-blind, randomised controlled trial in two teaching hospitals. We screened 183 patients for inclusion. 111 were randomly allocated either intensive management or routine care. Primary outcome measures were mean fall in disease activity score and proportion of patients with a good response (defined as a disease activity score <2.4 and a fall in this score from baseline by >1.2). Analysis was by intention-to-treat. FINDINGS: One patient withdrew after randomisation and seven dropped out during the study. Mean fall in disease activity score was greater in the intensive group than in the routine group (-3.5 vs -1.9, difference 1.6 [95% CI 1.1-2.1], p<0.0001). Compared with routine care, patients treated intensively were more likely to have a good response (definition, 45/55 [82%] vs 24/55 [44%], odds ratio 5.8 [95% CI 2.4-13.9], p<0.0001) or be in remission (disease activity score <1.6; 36/55 [65%] vs 9/55 [16%], 9.7 [3.9-23.9], p<0.0001). Three patients assigned routine care and one allocated intensive management died during the study; none was judged attributable to treatment. INTERPRETATION: A strategy of intensive outpatient management of rheumatoid arthritis substantially improves disease activity, radiographic disease progression, physical function, and quality of life at no additional cost.

Capell H, McCarey D, Madhok R, Hampson R. · Centre for Rheumatic Diseases, The Royal Infirmary, Glasgow, Scotland. · J Rheumatol. · Pubmed #12375318 No free full text.

Abstract: OBJECTIVE: Evaluation of a complex and variable disease such as rheumatoid arthritis (RA) poses a challenge particularly over the medium to long term. A practical framework to evaluate clinically relevant outcomes over the long term is the "5D" approach of Fries, described in 1980. We describe the 20 year outcome in 52 survivors of a 123 patient cohort in terms of change in discomfort, disability, drug side effects, dollar costs, and deaths. METHODS: We studied 123 patients with RA allocated to their first disease modifying antirheumatic drug (DMARD) between 1977 and 1979. All were under the overall care of one physician over the 20 years and were maintained where possible taking a single DMARD. Baseline demographic variables, the Ritchie Articular Index (RAI), Lee functional index, and erythrocyte sedimentation rate (ESR) were initially recorded. The extent to which the demographic and disease variables contributed to need for joint replacement surgery was assessed. Therapies for comorbidity were also documented. RESULTS: At cohort inception mean age was 50 years, RAI was 35, and median disease duration 5.5 years. F:M ratio was 90:33; 96% of patients were positive for rheumatoid factor (RF). Initial median ESR was 55 mm/h. At 20 years, 9 patients (7% of original cohort, 14% of survivors) were lost to followup and 62 (50%) had died. In the 52 survivors RAI, a surrogate for disability, showed a significant improvement (p < 0.0001), but disability measured by Lee functional index showed a deterioration (p = 0.018); 50% underwent joint replacement surgery. Initial ESR and mean ESR over the first 10 years of followup were significantly higher in those who required surgery. Nonsteroidal antiinflammatory drug (NSAID) use declined, but at least 2 deaths and 4 renal deaths that may have been related to therapy were attributed to NSAID use. No unexpected DMARD toxicity or mortality occurred. Concomitant therapy for comorbidity, in particular for cardiovascular disease, osteoporosis, and gastrointestinal disease, increased: more than 60% were on these therapies at 20 year followup. CONCLUSION: Strategies to improve the outcome of RA in all dimensions should include: earlier referral for expert assessment; avoidance of NSAID gastrointestinal and nephrotoxicity; a more intensive effort to identify effective management of comorbidity and those likely to have a poor outcome. Such patients require sustained, intensive therapy to minimize later disability.

Crilly A, Bartlett JM, White A, Stirling D, Capell H, Madhok R. · University Department of Medicine, 10 Alexandra Parade, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. · Cytokine. · Pubmed #11145851 No free full text.

Abstract: A highly polymorphic AT rich repeat exists in the 3' flanking region of the IL-6 gene. Using Genescan analysis we studied this region of the IL-6 gene in 55 normals and 95 patients with rheumatoid arthritis (RA). The influence of alleles on need for early major joint surgery in RA patients was assessed. We identified nine alleles of which, G8, G7 and G4 were the most common (37% vs 36% vs 13%). RA surgery patients had an increase in the frequency of G7 compared to non-surgery and control populations (46% vs 27% vs 34%, respectively) and a decrease in G8 (22% vs 46% vs 43%, respectively). RA patients homozygous for G8 had a lower ESR than those homozygous for G7 (23 mm/h vs 36 mm/h) although this was not significant. We have determined these alleles and their distribution in a normal and RA population. Initial findings suggest G8 may be associated with lower erythrocyte sedimentation rate (ESR) and less severe RA. Although trends in allele distribution were observed, further studies in larger cohorts are required.