Rheumatoid Arthritis: Conaghan PG

Freeston JE, Bird P, Conaghan PG. · Chapel Allerton Hospital, University of Leeds, UK. · Curr Opin Rheumatol. · Pubmed #19339918 No free full text.

Abstract: PURPOSE OF REVIEW: This review describes the important role of MRI in rheumatoid arthritis (RA), exploring recent reliability and validity work, as well as the current use of MRI in clinical trials and practice. RECENT FINDINGS: Both bone oedema and erosions on MRI have been confirmed as representing osteitis and cortical bone defects, respectively, adding to what was already known about the validity of contrast enhanced synovium representing synovitis. An increasing number of studies have used MRI as an outcome measure with interest moving from disease-modifying antirheumatic drugs (DMARDs) to biological therapies and a more technical focus on dynamic imaging. In addition, low-field extremity MRI has been developed as a well tolerated, comfortable and convenient method for imaging assessment in clinical practice. SUMMARY: This review has highlighted both recent research advances as well as the future potential for MRI in RA, with the aim that MRI will become part of standard measures for RA clinical trials. With respect to extremity imaging, further work is required to provide useful clinical algorithms.

Keen HI, Lavie F, Wakefield RJ, D'Agostino MA, Hammer HB, Hensor E, Pendleton A, Kane D, Guerini H, Schueller-Weidekamm C, Kortekaas MC, Birrel F, Kloppenburg M, Stamm T, Watt I, Smolen JS, Maheu E, Dougados M, Conaghan PG. · Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, University of Leeds, Leeds, UK. · Ann Rheum Dis. · Pubmed #17704062 No free full text.

Abstract: OBJECTIVES: Painful osteoarthritis (OA) of the hand is common and a validated ultrasound (US) scoring system would be valuable for epidemiological and therapeutic outcome studies. US is increasingly used to assess peripheral joints, though most of the US focus in rheumatic diseases has been on rheumatoid arthritis. We aimed to develop a preliminary US hand OA scoring system, initially focusing on relevant pathological features with potentially high reliability. METHODS: A group of experts in the fields of OA, US and novel tool development agreed on domains and suggested scaling of the items to be used in US hand OA scoring systems. A multi-observer reliability exercise was then performed to evaluate the draft items. RESULTS: Synovitis (grey scale and Power Doppler) and osteophytes (representing activity and damage domains) were included and evaluated as the initial components of the scoring system. All three features were evaluated for their presence/absence and if present were scored using a 1-3 scale. The reliability exercise demonstrated intra-reader kappa values of 0.444-1.0, 0.211-1.0 and 0.087-1.0 for grey scale synovitis, power Doppler and osteophytes respectively. Inter-reader reliability kappa values were 0.398, 0.327 and 0.530 grey-scale synovitis, power Doppler and osteophytes respectively. Without extensive standardisation, both intra- and inter-reader reliability were moderately good. CONCLUSIONS: The draft scoring system demonstrated substantive to almost perfect percentage exact agreement on the presence/absence of the selected OA features and moderate to substantive percentage exact agreement on semi-quantitative grading. This preliminary process provides a good basis from which to further develop an US outcome tool for hand OA that has the potential to be utilised in multicentre clinical trials.

Joshua F, Lassere M, Bruyn GA, Szkudlarek M, Naredo E, Schmidt WA, Balint P, Filippucci E, Backhaus M, Iagnocco A, Scheel AK, Kane D, Grassi W, Conaghan PG, Wakefield RJ, D'Agostino MA. · Department of Rheumatology, St. George Hospital, University of NSW, Sydney, Australia. · J Rheumatol. · Pubmed #17407235 No free full text.

Abstract: This report presents the results of a recent systematic review performed by the OMERACT Ultrasound Group on the metric properties of ultrasound for the detection of synovitis in inflammatory arthritis. Reviews were conducted for the hand, wrist, elbow, shoulder, knee, ankle, and foot; most reports were related to the hand and knee, and the most common disease process was rheumatoid arthritis. The review highlights the current gaps in the literature, including a lack of reliability data with respect to intra-occasion and intra- and inter-reader reliability. Current work by our group is addressing these issues.

Conaghan PG, Felson D, Gold G, Lohmander S, Totterman S, Altman R. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · Osteoarthritis Cartilage. · Pubmed #16713722 No free full text.

Abstract: Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both OA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful OA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the OA process and its response to therapy.

Hunter DJ, Conaghan PG. · Boston University Clinical Epidemiology Research and Training Unit, and the Department of Medicine at Boston Medical Center, Boston, Massachussetts 02118, USA. · Curr Opin Rheumatol. · Pubmed #16462521 No free full text.

Abstract: PURPOSE OF REVIEW: This review describes the advances in knowledge of outcomes that have occurred recently as a result of imaging research in both osteoarthritis and rheumatoid arthritis. RECENT FINDINGS: Recent imaging advances in osteoarthritis have offered insights into fundamental questions including the cause of pain and reasons for disease progression. Although ongoing disease modification clinical drug trials in osteoarthritis mostly use standardized plain radiographs to monitor structural changes in the joint, magnetic resonance imaging is rapidly evolving as a method of monitoring joint structure and with time may become the preferred method of monitoring this feature in osteoarthritis clinical trials. The past decade has seen major advances in the treatment of rheumatoid arthritis in which imaging determines whether individual agents or therapeutic regimens are structure modifying. Although conventional radiography remains the gold standard for assessing structural progression in rheumatoid arthritis, growing work on the performance metrics of magnetic resonance imaging has resulted in its increasing use in trials. Ultrasonography shows preliminary promise as a useful outcome measure. SUMMARY: Recent advances in imaging are improving our understanding of the etiopathogenesis and treatment of persons with osteoarthritis and rheumatoid arthritis. Complex challenges face us over the coming years as clinicians and researchers grapple with the use of these new techniques, the insights they may provide, and their clinical application.

Conaghan PG, McQueen FM, Peterfy CG, Lassere MN, Ejbjerg B, Bird P, O'Connor PJ, Haavardsholm E, Edmonds JP, Emery P, Genant HK, Ostergaard M, Anonymous00379. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · J Rheumatol. · Pubmed #16331788 No free full text.

Abstract: Magnetic resonance imaging (MRI) has now been used extensively in cross-sectional and observational studies as well as in controlled clinical trials to assess disease activity and joint damage in rheumatoid arthritis (RA). MRI measurements or scores for erosions, bone edema, and synovitis have been developed and validated by several groups. The OMERACT criteria require that outcome measures demonstrate adequate validity, discriminative power, and feasibility if they are to be useful in clinical trials. Specific performance targets for these criteria depend on the scientific, regulatory, logistical, and financial context of the study in question. We review the extent to which MRI assessments of joint erosion, bone edema, and synovitis fulfil these criteria, particularly as they relate to proof-of-concept RA clinical trials.

Keen HI, Brown AK, Wakefield RJ, Conaghan PG. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. · Rheum Dis Clin North Am. · Pubmed #16287592 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disorder primarily affecting the synovium and is characterized by destruction of bone and cartilage. Early diagnosis and treatment of RA can improve disease outcomes substantially. Magnetic resonance imaging and musculoskeletal ultrasonography may facilitate early diagnosis and aid the targeting of intensive therapy. Magnetic resonance imaging and musculoskeletal ultrasonography also are able to monitor temporal changes in disease activity (ie, synovitis) and damage (ie, erosions). These imaging modalities are likely to be increasingly used in the management of early rheumatoid arthritis to ensure the best patient outcomes, although more work is required to determine their optimal roles.

Brown AK, Wakefield RJ, Conaghan PG, Karim Z, O'Connor PJ, Emery P. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, University of Leeds, Leeds General Infirmary, UK. · Clin Exp Rheumatol. · Pubmed #15552510 No free full text.

Abstract: Imaging techniques such as musculoskeletal ultrasonography (MUS) and magnetic resonance imaging (MRI) are playing an increasingly important role in the assessment of patients with inflammatory arthritis. Such modalities are now used routinely in the evaluation of joint, tendon and soft tissue inflammation and bone damage in many early arthritis clinics. They have the ability to directly visualise, characterise and quantify the earliest inflammatory changes and have proved not only to be useful additional complimentary clinical tools to improve the speed and accuracy of diagnosis, direct appropriate treatment, monitor response to therapy, measure disease progression and outcome but also continue to contribute to our understanding of disease pathogenesis. These imaging methods may therefore offer a significant advantage as they endorse the principles of early diagnosis and optimal targeted therapy essential to providing the most favourable long term outcome for patients with inflammatory arthritis. This article reviews the current evidence supporting the role of MUS and MRI in the assessment of patients with inflammatory arthritis.

Wakefield RJ, Conaghan PG, Jarrett S, Emery P. · Academic Department of Musculoskeletal Medicine, Leeds General Infirmary, UK. · Curr Opin Rheumatol. · Pubmed #15201608 No free full text.

Abstract: New imaging techniques such as ultrasound and MRI are likely to play increasing roles in the future management of patients with inflammatory arthritis, particularly those with rheumatoid arthritis and spondyloarthropathies. Ultrasound has a number of distinct advantages including its ability to scan multiple joints, safety, and immediately availability in clinic. MRI, however, is more sensitive and has a greater field of view because of its tomographic nature. Both modalities have the added advantage over radiography in that they can image soft tissue as well as bone. Dual X-ray absorptiometry already has an established role to play in the assessment of osteoporosis, but new techniques such as digital radiogrametry, quantitative CT, and ultrasound potentially will have a more important role to play in the future.

Wakefield RJ, Kong KO, Conaghan PG, Brown AK, O'Connor PJ, Emery P. · Academic Department of Musculoskeletal Medicine, General Infirmary at Leeds, Leeds, United Kingdom. · Clin Exp Rheumatol. · Pubmed #14969049 No free full text.

Abstract: Advances in ultrasound (US) and magnetic resonance imaging (MRI) techniques have provided new methods for evaluating early rheumatoid arthritis (RA). Their diagnostic properties in terms of detecting primary pathology of RA (i.e., erosions, bone changes, synovitis, tenosynovitis, and effusion) are reviewed. High-resolution US plays a significant role in therapeutic and diagnostic procedures. MRI also assists in the understanding of RA pathogenesis and joint mechanics.

Quinn MA, Conaghan PG, Emery P. · Rheumatology and Rehabilitation Research Unit, University of Leeds, Leeds, UK. · Rheumatology (Oxford). · Pubmed #11709604 links to  free full text

Abstract: OBJECTIVE: The concepts of early intervention and early arthritis clinics for the management of rheumatoid arthritis (RA) were introduced almost a decade ago. The evidence for these is diverse and the best therapeutic approach remains vehemently debated. This review addresses these issues. METHODS: The MEDLINE database was searched to identify relevant papers satisfying inclusion criteria for disease duration and no previous use of disease-modifying anti-rheumatic drugs (DMARDs). Where possible, evidence was obtained from randomized controlled trials. We selected the most relevant topics to best justify early therapeutic intervention in RA. RESULTS: The benefit of DMARDs over placebo and delayed therapy is unquestionable from the studies presented, with reduction in bone damage and preservation of function. Through prevention of disability, early treatment should be the most cost-effective approach. The evidence presented supports the use of DMARDs when the diagnosis of RA is first made. Delay in treatment may result in irreversible damage. There is insufficient evidence to recommend combination therapy for all patients at disease onset. Further research into newer therapies is required before their routine first-line use is recommended. CONCLUSIONS: Early therapeutic intervention in RA reduces long-term disability and joint damage. Optimal management appears to be the early identification of non-responders and targeted combination therapy. Biological therapies have the potential to revolutionize the treatment of early RA.

McGonagle D, Conaghan PG, Wakefield R, Emery P. · Rheumatology and Rehabilitation Research Unit, University of Leeds, 36 Clarendon Road, Leeds, LS2 9NZ, UK. · Best Pract Res Clin Rheumatol. · Pubmed #11358417 No free full text.

Abstract: Radiography is the most widely utilized imaging modality for early rheumatoid arthritis, determination of radiographic progression remaining a crucial part of the evaluation of therapy. Conventional radiography is, however, insensitive for showing bone damage in early disease and is totally unsuitable for assessing synovial inflammation. The recognition of these limitations has led to intense interest in the multiplanar imaging capabilities of magnetic resonance imaging in rheumatoid arthritis and to an increasing use of ultrasonography for assessing synovitis and bone damage. This chapter discusses the role of radiography in early rheumatoid arthritis and the emerging use and role of magnetic resonance imaging and ultrasonography in evaluating synovitis and bone damage. The relationship between synovitis and bone damage is also addressed in the light of recent magnetic resonance imaging observations.

Conaghan PG, Green MJ, Emery P. · Rheumatology and Rehabilitation Research Unit, University of Leeds, England. · Baillieres Best Pract Res Clin Rheumatol. · Pubmed #10652640 No free full text.

Abstract: Currently the diagnosis of rheumatoid arthritis (RA) may be difficult; the ACR criteria appear most sensitive and specific in long-standing disease. Without clear definition or diagnostic criteria for early disease it is difficult to define late or established RA. The distinction between early and established RA has been further blurred by recent imaging studies that suggest even in what is currently termed early disease, there is evidence of joint damage. The natural history of RA suggests that most patients with clinic-diagnosed RA have a progressively disabling course, but evidence is growing that modern therapeutic strategies result in better long-term outcomes, especially when applied early in the disease course. In established disease, quantitative markers such as C-reactive protein (CRP) give prognostic information, but in the pre-erosive, early phase of the disease the qualitative markers such as rheumatoid factor (RF) and shared epitope are crucial. As rheumatologists, our major aims must remain: (1) to diagnose the disease as early as possible; (2) to identify those patients with poor prognosis who will benefit most from targeted therapy; and (3) to aim for more intensive disease control irrespective of disease duration.

Conaghan PG, McGonagle D, Wakefield R, Emery P. · Rheumatology and Rehabilitation Unit, University of Leeds, UK. · Clin Exp Rheumatol. · Pubmed #10589355 No free full text.

Abstract: Conventional radiology (CR) is a major tool for the diagnosis and assessment of early arthritis. However, CR does not image the primary pathology of rheumatoid arthritis (RA), i.e. the synovium, and is insensitive for radiological erosions. New techniques, particularly magnetic resonance imaging (MRI) and ultrasonography (US) have shown their potential to improve on the sensitivity of CR. This article reviews the current status of this approach in early disease.

Marzo-Ortega H, McGonagle D, Rhodes LA, Tan AL, Conaghan PG, O'Connor P, Tanner SF, Fraser A, Veale D, Emery P. · Consultant Rheumatologist, Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK. · Ann Rheum Dis. · Pubmed #17185324 No free full text.

Abstract: BACKGROUND: Psoriatic arthritis (PsA) is commonly associated with bone pathology, including entheseal new bone formation and osteolysis. On MRI, areas of active clinical involvement are represented by bone oedema and synovitis. Aim: To assess the impact of infliximab on bone oedema in PsA as shown by MRI. METHODS: 18 patients with joint swelling, psoriasis and seronegativity for rheumatoid factor received four infusions of infliximab, 3 mg/kg, in combination with methotrexate. MRI of the affected hand (12 patients) or knee joints (6 patients) was performed before and after treatment. The primary outcome was the assessment of bone oedema and synovitis at 20 weeks as shown by MRI. Secondary outcomes included the American College of Rheumatology (ACR) response criteria, psoriasis skin scores (Psoriasis Area and Severity Index (PASI)) and a quality of life measure (Psoriatic Arthritis Quality of Life (PsAQoL)). RESULTS: At baseline, bone oedema was seen in 50% of patients (seven hands and two knees) in 30% of scanned joints, and this improved or resolved in all cases in the hand joints (p = 0.018) and in one knee joint at 20 weeks. Synovitis was found to be reduced in 90% of cases on MRI. Likewise, a significant improvement in all clinical outcomes, including PASI (p = 0.003) and PsAQoL (p = 0.006) was seen at week 20. 65% (n = 11) of the patients achieved an ACR response, of whom 45% had ACR70 or above and 54% had ACR20 or ACR50. CONCLUSIONS: Infliximab treatment is associated with dramatic improvements in MRI-determined bone oedema in PsA in the short term. It remains to be determined whether infliiximib treatment is the cause for prevention of new bone formation, bone fusion or osteolysis in PsA as shown by radiography.

Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, Wakefield RJ, O'Connor PJ, Emery P. · Chapel Allerton Hospital, University of Leeds, Leeds, UK. · Arthritis Rheum. · Pubmed #17133543 links to  free full text

Abstract: OBJECTIVE: More timely and effective therapy for rheumatoid arthritis (RA) has contributed to increasing rates of clinical remission. However, progression of structural damage may still occur in patients who have satisfied remission criteria, which suggests that there is ongoing disease activity. This questions the validity of current methods of assessing remission in RA. The purpose of this study was to test the hypothesis that modern joint imaging improves the accuracy of remission measurement in RA. METHODS: We studied 107 RA patients receiving disease-modifying antirheumatic drug therapy who were judged by their consultant rheumatologist to be in remission and 17 normal control subjects. Patients underwent clinical, laboratory, functional, and quality of life assessments. The Disease Activity Score 28-joint assessment and the American College of Rheumatology remission criteria, together with strict clinical definitions of remission, were applied. Imaging of the hands and wrists using standardized acquisition and scoring techniques with conventional 1.5T magnetic resonance imaging (MRI) and ultrasonography (US) were performed. RESULTS: Irrespective of which clinical criteria were applied to determine remission, the majority of patients continued to have evidence of active inflammation, as shown by findings on the imaging assessments. Even in asymptomatic patients with clinically normal joints, MRI showed that 96% had synovitis and 46% had bone marrow edema, and US showed that 73% had gray-scale synovial hypertrophy and 43% had increased power Doppler signal. Only mild synovial thickening was seen in 3 of the control subjects (18%), but no bone marrow edema. CONCLUSION: Most RA patients who satisfied the remission criteria with normal findings on clinical and laboratory studies had imaging-detected synovitis. This subclinical inflammation may explain the observed discrepancy between disease activity and outcome in RA. Imaging assessment may be necessary for the accurate evaluation of disease status and, in particular, for the definition of true remission.

Quinn MA, Conaghan PG, O'Connor PJ, Karim Z, Greenstein A, Brown A, Brown C, Fraser A, Jarret S, Emery P. · Academic Unit of Musculoskeletal Disease, First Floor, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. · Arthritis Rheum. · Pubmed #15641102 links to  free full text

Abstract: OBJECTIVE: Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12-month double-blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poor-prognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months. METHODS: All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months. RESULTS: Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C-reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between-group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05). CONCLUSION: Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.

Davys HJ, Turner DE, Helliwell PS, Conaghan PG, Emery P, Woodburn J. · Health Department, The Leeds General Infirmary, University of Leeds, 36 Clarendon Road, Leeds LS2 9NZ, UK. · Rheumatology (Oxford). · Pubmed #15479752 links to  free full text

Abstract: OBJECTIVE: To compare forefoot pain, pressure and function before and after normal and sham callus treatment in rheumatoid arthritis (RA). Patients and METHODS: Thirty-eight RA patients were randomly assigned to normal (NCT group) or sham (SCT) scalpel debridement. The sham procedure comprised blunt-edged scalpel paring of the callus which delivered a physical stimulus but left the hyperkeratotic tissue intact, the procedure being partially obscured from the patient. Forefoot pain was assessed using a 100 mm visual analogue scale (VAS), pressure using a high-resolution foot pressure scanner and function using the spatial-temporal gait parameters measured on an instrumented walkway. Radiographic scores of joint erosion were obtained for metatarsophalangeal (MTP) joints with and without overlying callosities. The trial consisted of a randomized sham-controlled phase evaluating the immediate same-day treatment effect and an unblinded 4-week follow-up phase. RESULTS: During the sham-controlled phase, forefoot pain improved in both groups by only 3 points on a VAS and no statistically significant between-group difference was found (P = 0.48). When data were pooled during the unblinded phase, the improvement in forefoot pain reached a peak after 2 days and gradually lessened over the next 28 days. Following debridement, peak pressures at the callus sites decreased in the NCT group and increased in the SCT group, but there was no statistically significant between-group difference (P = 0.16). The area of and duration of contact of the callus site on the ground remained unchanged following treatment in both groups. Following debridement, walking speed was increased, the stride-length was longer and the double-support time shorter in both groups; however, between-group differences did not reach levels of statistical significance. MTP joints with overlying callus were significantly more eroded than those without (P = 0.02). CONCLUSIONS: Treatment of painful plantar callosities in RA using scalpel debridement lessened forefoot pain but the effect was no greater than sham treatment. Localized pressure or gait function was not significantly improved following treatment.

Conaghan PG, O'Connor P, McGonagle D, Astin P, Wakefield RJ, Gibbon WW, Quinn M, Karim Z, Green MJ, Proudman S, Isaacs J, Emery P. · University of Leeds and Leeds General Infirmary, Leeds, UK. · Arthritis Rheum. · Pubmed #12528105 links to  free full text

Abstract: OBJECTIVE: To simultaneously image bone and synovium in the individual joints characteristically involved in early rheumatoid arthritis (RA). METHODS: Forty patients with early, untreated RA underwent gadolinium-enhanced magnetic resonance imaging (MRI) of the second through fifth metacarpophalangeal joints of the dominant hand at presentation, 3 months, and 12 months. In the first phase (0-3 months), patients were randomized to receive either methotrexate alone (MTX) or MTX and intraarticular corticosteroids (MTX + IAST) into all joints with clinically active RA. The MTX-alone group received no further corticosteroids until the second phase (3-12 months), when both groups received standard therapy. RESULTS: In the first phase, MTX + IAST reduced synovitis scores more than MTX alone. There were significantly fewer joints with new erosions on MRI in the former group compared with the latter. During the second phase, the synovitis scores were equivalent and a similar number of joints in each group showed new erosions on MRI. In both phases, there was a close correlation between the degree of synovitis and the number of new erosions, with the area under the curve for MRI synovitis the only significant predictor of bone damage progression. In individual joints, there was a threshold effect on new bone damage related to the level of synovitis; no erosions occurred in joints without synovitis. CONCLUSION: In early RA, synovitis appears to be the primary abnormality, and bone damage occurs in proportion to the level of synovitis but not in its absence. In the treatment of patients with RA, outcome measures and therapies should focus on synovitis.

Proudman SM, Conaghan PG, Richardson C, Griffiths B, Green MJ, McGonagle D, Wakefield RJ, Reece RJ, Miles S, Adebajo A, Gough A, Helliwell P, Martin M, Huston G, Pease C, Veale DJ, Isaacs J, van der Heijde DM, Emery P. · University of Leeds, UK. · Arthritis Rheum. · Pubmed #10943871 links to  free full text

Abstract: OBJECTIVE: To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ). METHODS: Eighty-two consecutive patients presenting with new, untreated RA of less than 12 months' duration who fulfilled criteria for poor long-term outcome were randomized to receive either combination therapy (n = 40) or SSZ alone (n = 42). The primary outcome measures were remission and American College of Rheumatology (ACR) criteria for 20% improvement at 48 weeks. RESULTS: After 48 weeks, the numbers of patients who met the ACR criteria for 20% improvement were not significantly different between the two groups (combination 58% versus SSZ 45%), and similar numbers of patients had persisting clinical remission (approximately 10% both groups). During the first 3 months, there were significantly greater reductions in parameters of disease activity in the combination group. By 24 weeks, the swollen and tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen significantly in both groups, with a greater improvement in the swollen and tender joint count in the combination group. At 48 weeks, the radiographic damage score had increased by a median of 1 (range 0-42.5) in the combination group and 1.25 (range 0-72.5) in the SSZ group (P = 0.28; although there were significant differences in the scores for the right hand). There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group (1 of 40 versus 10 of 42; P = 0.007). In the combination group, dose reduction was needed in 22.5% because of hypertension and in 22.5% because of elevated creatinine levels. Over 48 weeks, serum creatinine increased in both groups, but particularly in the combination arm. CONCLUSION: In poor-prognosis RA patients, "aggressive" combination therapy led to more rapid disease suppression but did not result in significantly better ACR response or remission rates. This suggests that in poor-prognosis disease, an approach based on identifying patients with poor treatment responses before extra therapy is added ("step-up" approach) may be more appropriate than the use of combination therapy in all patients from the outset.

Saleem B, Brown AK, Keen H, Nizam S, Freeston J, Karim Z, Quinn M, Wakefield R, Hensor E, Conaghan PG, Emery P. · University of Leeds, Chapel Allerton Hospital, Leeds, UK. · Arthritis Rheum. · Pubmed #19565512 No free full text.

Abstract: OBJECTIVE: For patients with rheumatoid arthritis (RA) in remission who are receiving disease-modifying antirheumatic drugs (DMARDs), radiographic progression correlates with imaging-detected synovitis as measured by power Doppler activity. In contrast, patients with disease in remission who are receiving the combination of tumor necrosis factor (TNF) blockade with methotrexate (MTX) (combination treatment) have reduced radiographic damage for the equivalent clinical state. We undertook this study to determine whether the difference in radiographic outcome is a result of more complete suppression of imaging-detected synovitis. METHODS: One hundred patients with RA in remission (Disease Activity Score in 28 joints [DAS28] <2.6) for at least 6 months while receiving either combination treatment (n = 50) or DMARDs (n = 50) were matched for clinical variables. Ultrasound of metacarpophalangeal joints 1-5 and the wrist joints was performed. Remission according to imaging results was defined as a score of 0 for both grey scale synovitis and power Doppler activity. RESULTS: In patients receiving combination treatment or DMARDs (median DAS28 1.65 versus 1.78, median disease duration 120 months versus 90 months, and median duration of remission 13 months versus 18 months), the proportion with remission according to imaging results was not significantly different (10% versus 16%, respectively). The combination treatment group had more grey scale synovitis (P < 0.001) but similar power Doppler activity (48% versus 60%, respectively; P = 0.229) in any joint as compared with the DMARD group. Results were not affected by stratification for duration of disease or remission. CONCLUSION: In RA patients with disease in remission, imaging-detected synovitis persists, with power Doppler activity seen in >/=48% of the patients regardless of therapy. These results suggest that superior radiographic outcomes in patients treated with the combination of TNF blockade and MTX may not be due to complete suppression of imaging-detected synovitis.

Ostör AJ, Conaghan PG. · School of Clinical Medicine, University of Cambridge, Clinical Research Unit. · Practitioner. · Pubmed #19418700 No free full text.

This publication has no abstract.

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.

Covic T, Pallant JF, Tennant A, Cox S, Emery P, Conaghan PG. · School of Psychology, University of Western Sydney, Penrith South DC 1797, NSW, Australia. · BMC Musculoskelet Disord. · Pubmed #19200388 links to  free full text

Abstract: BACKGROUND: Depression is common in rheumatoid arthritis (RA), however reported prevalence varies considerably. Two frequently used instruments to identify depression are the Center for Epidemiological Studies Depression (CES-D) scale, and the Hospital Anxiety and Depression Scale (HADS). The objectives of this study were to test if the CES-D and HADS-D (a) satisfy current modern psychometric standards for unidimensional measurement in an early RA sample; (b) measure the same construct (i.e. depression); and (c) identify similar levels of depression. METHODS: Data from the two scales completed by patients with early RA were fitted to the Rasch measurement model to show that (a) each scale satisfies the criteria of fit to the model, including strict unidimensionality; (b) that the scales can be co-calibrated onto a single underlying continuum of depression and to (c) examine the location of the cut points on the underlying continuum as indication of the prevalence of depression. RESULTS: Ninety-two patients with early RA (62% female; mean age = 56.3, SD = 13.7) gave 141 sets of paired CES-D and HAD-D data. Fit of the data from the CES-D was found to be poor, and the scale had to be reduced to 13 items to satisfy Rasch measurement criteria whereas the HADS-D met model expectations from the outset. The 20 items combined (CES-D13 and HADS-D) satisfied Rasch model expectations. The CES-D gave a much higher prevalence of depression than the HADS-D. CONCLUSION: The CES-D in its present form is unsuitable for use in patients with early RA, and needs to be reduced to a 13-item scale. The HADS-D is valid for early RA and the two scales measure the same underlying construct but their cut points lead to different estimates of the level of depression. Revised cut points on the CES-D13 provide comparative prevalence rates.

Marzo-Ortega H, Tanner SF, Rhodes LA, Tan AL, Conaghan PG, Hensor EM, Radjenovic A, O'Connor P, Emery P, McGonagle D. · Academic Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Chapel Allerton Hospital, Leeds LS74SA, UK. · Scand J Rheumatol. · Pubmed #19177263 No free full text.

Abstract: OBJECTIVES: The aim of this study was to determine whether magnetic resonance imaging (MRI)-related entheseal changes including osteitis and extracapsular oedema could be used to differentiate between metacarpophalangeal (MCP) joint involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: Twenty patients (10 each with early RA and PsA) had dynamic contrast-enhanced MRI (DCE-MRI) of swollen MCP joints. Synovitis and tenosynovitis was calculated using quantitative analysis including the degree and kinetics of enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone oedema were scored using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) proposals. Entheseal-related features including extracapsular soft tissue enhancement or regions of diffuse bone oedema were also evaluated. RESULTS: MRI was not able to differentiate at the group level between both cohorts on the basis of entheseal-related disease but a subgroup of PsA patients had diffuse extracapsular enhancement (30%) or diffuse bone oedema (20%). The RA patient group had a greater degree of MCP synovitis (p<0.0001) and tenosynovitis than PsA patients (p<0.0001). There were no significant differences in either the total number of erosions (p = 0.315) or the presence of periarticular bone oedema (p = 0.105) between the groups. CONCLUSION: Although conventional MRI shows evidence of an enthesitis-associated pathology in the MCP joints in PsA, this is not sufficiently common to be of diagnostic utility.