Rheumatoid Arthritis: Kiely PD

Deighton CM, George E, Kiely PD, Ledingham J, Luqmani RA, Scott DG. · No affiliation provided · Rheumatology (Oxford). · Pubmed #16527881 links to  free full text

This publication has no abstract.

Kiely PD. · Department of Rheumatology, St George's Healthcare NHS Trust, London SW17 0QT. · Hosp Med. · Pubmed #15624449 No free full text.

Abstract: Autoimmune diseases make up a large proportion of chronic disease care. Inducing remission by immunosuppression remains the cornerstone of long-term management. This article reviews the place of leflunomide in clinical practice and outlines its potential applications beyond its licenced indication, rheumatoid arthritis.

Kiely PD, Johnson DM. · Department of Rheumatology, St George's Healthcare NHS Trust, Blackshaw Road, London SW17 0QT, UK. · Rheumatology (Oxford). · Pubmed #12048288 links to  free full text

Abstract: OBJECTIVE: To study the safety and efficacy of infliximab plus leflunomide combination therapy in adult rheumatoid arthritis (RA). METHODS: Twenty patients with active RA received leflunomide 100 mg for 3 days followed by 20 mg daily for 32 weeks. At week 2 all patients started infliximab 3 mg/kg, and received a further four infusions at weeks 4, 8, 16 and 24. RESULTS: Adverse events led to 11 patients being withdrawn before the end of the study. The commonest adverse event was pruritus associated with an eczematous rash. Other serious reactions included infliximab infusion reactions in four patients and Stevens-Johnson syndrome in one. There was no relationship between the serum concentration of A77 1726, the active metabolite of leflunomide, and adverse events. The mean Disease Activity Score (DAS28) fell from 7.18 at week 0 to 5.18 (P<0.0001, paired t-test) at week 4 and remained between 3.85 and 4.85 up to week 32. In those patients remaining on treatment, more than 80% achieved an ACR20 response from week 8 to week 28, and up to 46% achieved an ACR70 response. CONCLUSION: Infliximab plus leflunomide combination therapy appears to be highly efficacious in the treatment of adult RA. However, widespread use may be limited by adverse events, which were common and in some cases severe.

Kiely PD, Brown AK, Edwards CJ, O'Reilly DT, Ostör AJ, Quinn M, Taggart A, Taylor PC, Wakefield RJ, Conaghan PG. · Department of Rheumatology, St Georges Healthcare NHS Trust, London, UK. · Rheumatology (Oxford). · Pubmed #19401359 No free full text.

Abstract: OBJECTIVE: RA has a substantial impact on both patients and healthcare systems. Our objective is to advance the understanding of modern management principles in light of recent evidence concerning the condition's diagnosis and treatment. METHODS: A group of practicing UK rheumatologists formulated contemporary management principles and clinical practice recommendations concerning both diagnosis and treatment. Areas of clinical uncertainty were documented, leading to research recommendations. RESULTS: A fundamental concept governing treatment of RA is minimization of cumulative inflammation, referred to as the inflammation-time area under the curve (AUC). To achieve this, four core principles of management were identified: (i) detect and refer patients early, even if the diagnosis is uncertain: patients should be referred at the first suspicion of persistent inflammatory polyarthritis and rheumatology departments should provide rapid access to a diagnostic and prognostic service; (ii) treat RA immediately: optimizing outcomes with conventional DMARDs and biologics requires that effective treatment be started early-ideally within 3 months of symptom onset; (iii) tight control of inflammation in RA improves outcome: frequent assessments and an objective protocol should be used to make treatment changes that maintain low-disease activity/remission at an agreed target; (iv) consider the risk-benefit ratio and tailor treatment to each patient: differing patient, disease and drug characteristics require long-term monitoring of risks and benefits with adaptations of treatments to suit individual circumstances. CONCLUSION: These principles focus on effective control of the inflammatory process in RA, but optimal uptake may require changes in service provision to accommodate appropriate care pathways.

Reynolds PP, Heron C, Pilcher J, Kiely PD. · Department of Rheumatology, St. Georges Healthcare NHS Trust, London, UK. · Skeletal Radiol. · Pubmed #19259659 No free full text.

Abstract: OBJECTIVES: This study aimed to determine whether a range of single-time-point ultrasound (US) measures of synovial disease and serologic characteristics were able to predict progression of US-defined erosive disease in patients with established rheumatoid arthritis (RA). MATERIALS AND METHODS: Forty patients were studied prospectively. At baseline, subjective US measures of bone damage and synovial disease, including grayscale and power Doppler (PD) scores pre- and post-Sonovue contrast, were obtained from one proximal inter-phalangeal or metacarpo-phalangeal joint per patient. After a minimum of 2 years, the same joints were scanned to obtain a new US erosion score. RESULTS: Follow-up US erosion scores were obtained in 25 joints. Progressive US determined that bone damage occurred in 12/25 joints, including four of eight treated with anti-tumor necrosis factor therapy. Baseline erosion scores were significantly higher in joints that did not show progressive bone damage in the entire cohort (p = 0.05, n = 25) and a subgroup treated with disease-modifying anti-rheumatic drugs (p = 0.015, n = 17). There were no other significant differences in baseline US or serologic scores between joints that developed progressive damage and those that did not. CONCLUSIONS: The majority of single-time-point US measures of synovial disease were not able to identify metacarpo-phalangeal or inter-phalangeal joint destined to develop progressive US-determined bone damage in patients with established RA. This may reflect the use of single-time-point measures, insensitivity of the US erosion score, and the long duration of RA disease in this study.

Rachapalli SM, Kiely PD, Bourke BE. · St George's Hospital, Blackshaw Road, Tooting, London, UK. · Clin Rheumatol. · Pubmed #19205787 No free full text.

Abstract: Chronic inflammatory autoimmune conditions like rheumatoid arthritis and systemic lupus erythematosus are associated with an increased risk of accelerated atherosclerosis (ATS). Very limited data are available about the incidence of ATS in patients with primary Sjogren's syndrome (PSS). Ankle brachial index (ABI) is a recognized method of detecting subclinical atherosclerosis. The objective of this study was to compare the prevalence of abnormal ABI in patients with PSS and in controls without PSS. Twenty-five PSS patients were compared with an age-, ethnicity-, and sex-matched control group. Traditional risk factors such as smoking, high blood pressure, blood sugar, lipids, and family history of atherosclerosis were assessed in both groups. Baseline clinical and laboratory features of PSS patients were recorded. ABI was measured in both groups. ABI less than 1.0 is considered abnormal. Fifty individuals (25 in each group) were studied. PSS patients and controls did not differ significantly in age, sex, and ethnicity. The prevalence of traditional cardiovascular risk factors was the same in both groups. Five out of 25 PSS patients (20%) had an ABI < 1.0 compared to one of 25 (4%) in the control group [P = 0.189 (odds ratio (OR) = 6.000 and 95% confidence interval (CI) 0.6464 to 55.692)]. Eight out of 25 PSS patients (32%) had disease duration of more than 10 years. This group of patients had a higher prevalence of low ABI compared to the individuals with lesser disease duration [P = 0.02 (OR = 16, 95% CI 1.38 to 185)]. PSS patients had a higher prevalence of low ABI, although this did not reach statistical significance. The subgroup of PSS patients with a longer duration of disease had a significantly lower ABI. This study was underpowered and a larger study is required to confirm the findings of this pilot study.

Hameed B, Pilcher J, Heron C, Kiely PD. · Department of Rheumatology, St George's Healthcare NHS Trust, Blackshaw Road, London SW17 0QT, UK. · Rheumatology (Oxford). · Pubmed #18281367 No free full text.

Abstract: OBJECTIVES: Ultrasound (US) provides measurements of synovial morphology and vascularity. However, on an individual joint basis in RA, US measures do not relate well to clinical signs. This study investigates the relationship between composite US measures and the 28-joint disease activity score (DAS28), its components and acute phase markers in adult RA. METHODS: RA synovial disease activity was recorded in 50 patients by: (i) the DAS28 score; (ii) ESR and CRP; and (iii) US using Grey scale (GS) and power Doppler (PD) measures of PIP and MCP joints to derive composite US scores based on abnormal counts and severity. A total of 25 control subjects were studied to define normal US appearances. The relation between each measure of synovial disease was determined by Spearman correlation analysis. RESULTS: There was a significant relation between the DAS28 and the GS joint count (GSJC, Spearman's r = 0.4; P = 0.004) and severity score (GSJS, r = 0.34; P = 0.016) and the PD joint count (PDJC, r = 0.32; P = 0.028). There was a significant relation between the ESR and PDJC (r = 0.37; P = 0.007) and PD joint severity score (PDJS, r = 0.38; P = 0.006) and between the CRP and PDJS (r = 0.29; P = 0.04). The remaining components of the DAS28 related poorly to all US measures, except the tender joint count, which related significantly to the GS but not the PD measures. CONCLUSIONS: Composite US markers of synovial disease relate significantly to the DAS28 score and ESR/CRP in adult RA, but not as well with individual clinical joint counts and the patient's global assessment.

Rees JD, Pilcher J, Heron C, Kiely PD. · Department of Rheumatology, St George's Healthcare NHS Trust, London, UK. · Rheumatology (Oxford). · Pubmed #16899500 links to  free full text

Abstract: OBJECTIVES: Synovitis in rheumatoid arthritis (RA) is assessed clinically by the presence of joint tenderness and swelling. Synovial thickening and increased vascularity may also be detected by high-resolution ultrasonography (US) and power Doppler (PD). This study investigated the relationship between clinical and sonographic features of synovial disease utilizing US, PD and the contrast agent Sono-Vue. METHODS: Forty RA patients were recruited. One proximal inter-phalangeal or metacarpophalangeal joint was selected per patient, as being unambiguously either: swollen and tender, just swollen, just tender or neither swollen nor tender (Nil). Ten joints were selected per clinical group. On US, the mean synovial thickness was measured and synovial hypertrophy and erosions were graded subjectively. Synovial vascularity demonstrated by PD was scored subjectively pre- and post-contrast. RESULTS: All grades of synovial vascularity were found in each clinical group including the Nil group. There were significant differences between the four clinical groups for both synovial hypertrophy (P = 0.024) and PD scores pre- (P = 0.022) and post- (P = 0.039) contrast. Tender-only joints showed significantly less vascularity than other groups. Post-contrast, the median PD scores increased in all but the Nil group, in some cases from the normal to abnormal range. CONCLUSION: Synovitis demonstrated by US and PD is not predicted by patterns of disease as described by joint swelling and tenderness despite unambiguous selection of joints. Synovial vascularity was the least in tender-only joints and was heterogeneous in all other groups, including Nil joints. These findings question the reliability of traditional clinical signs in RA synovitis assessment.

Kiely PD, Helbert MR, Miles J, Oliveira DB. · Departments of Rheumatology, Immunology and Renal Medicine, St George's Hospital Medical School, London, UK. · Clin Exp Immunol. · Pubmed #10792390 links to  free full text

Abstract: We set out to examine the effect of gold treatment on the Th2-dependent antibodies IgG4 and IgE in relation to other IgG subclasses in patients with rheumatoid arthritis (RA). Eighty-five gold-treated RA patients and 82 RA controls were studied. Serum IgG subclass concentrations were measured by ELISA, IgE was measured by automated enzyme immunoassay. Samples were studied serially in 13 gold-treated patients and in 11 patients with gold-induced adverse events. There was a significant reduction in the concentration of IgG1, IgG2 and IgG3 in gold-treated RA patients compared with RA controls (P 0.004-0.019), whereas IgG4 was less significantly reduced in gold-treated patients (P = 0.044) and there was no difference in IgE. In serial samples there was a significant fall in the concentration of IgG1 (P = 0.001), IgG2 (P = 0.001) and IgG3 (P = 0.026) with time but no change in IgG4 and IgE. The development of gold-induced adverse events was not associated with any change in the concentration of each IgG subclass or IgE. Deficiencies of IgG subclasses were found in 30% of gold-treated RA patients and 8.5% of RA controls, and were associated in gold-treated patients with a longer disease duration (P = 0.003) and with erosive disease (P = 0. 03). IgG2 was affected most frequently and in the majority of these cases subnormal specific IgG2 binding to widespread polysaccharide antigens (Pneumovax II) was found. Gold induces an overall immunosuppressant effect on IgG subclasses, with a deficiency in 21. 5%, adjusted for controls. The effect on the Th2-dependent antibodies IgG4 and IgE is less marked, suggesting a sparing of Th2 responses.

Ashok D, Ayliffe WH, Kiely PD. · No affiliation provided · Rheumatology (Oxford). · Pubmed #15827040 links to  free full text

This publication has no abstract.

Kiely PD. · No affiliation provided · Rheumatology (Oxford). · Pubmed #14681570 links to  free full text

This publication has no abstract.