Rheumatoid Arthritis: Watt I

Zhang W, Doherty M, Leeb BF, Alekseeva L, Arden NK, Bijlsma JW, Dincer F, Dziedzic K, Hauselmann HJ, Kaklamanis P, Kloppenburg M, Lohmander LS, Maheu E, Martin-Mola E, Pavelka K, Punzi L, Reiter S, Smolen J, Verbruggen G, Watt I, Zimmermann-Gorska I, Anonymous00031. · Dr W Zhang, Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Ann Rheum Dis. · Pubmed #18250111 No free full text.

Abstract: OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.

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.

Watt I, Cobby M. · Bristol Royal Infirmary, Bristol, UK. · Semin Arthritis Rheum. · Pubmed #11357168 No free full text.

Abstract: OBJECTIVES: The radiologic findings of a placebo-controlled, dose-ranging, multicenter, multinational trial have been reported previously. Radiographs were evaluated using the Larsen scoring method and Erosion Joint Count. After completion of the study, a subset of the films was read again using a modified Sharp score. This article will focus on the methodologies, scoring indices, and outcomes of the Larsen and Erosion Joint Count evaluations. Modified Sharp scores are presented in a separate article. METHODS: A 6-month, phase II, randomized, double-blind, placebo-controlled trial was conducted involving 472 patients with active rheumatoid arthritis. Patients from 41 centers in 11 countries were randomly selected to receive 30 mg/d, 75 mg/d, or 150 mg/d of recombinant human interleukin-1 receptor antagonist (IL-1ra) subcutaneously daily or placebo. Radiographic criteria were circulated to all centers, and the same 2 radiologists used the Larsen score and the Erosion Joint Count to score what was essentially a homogeneous film collection. At the completion of the study, a subset of radiographs also was read using the Genant-modified Sharp score. Patients in any of the treatment arms had the option of continuing in an extension trial for an additional 6 months, and those in the placebo arm had the option of being randomly placed into one of the treatment arms. RESULTS: The Larsen and Erosion Joint Count data from these patients confirm that at 24 weeks, patients receiving placebo worsened by an average of 6.49 Larsen units, whereas those receiving 30, 75, or 150 mg/d of IL-1ra worsened by 3.53, 4.19, and 3.90 Larsen units, respectively. Overall, patients receiving therapy worsened by an average of 3.86 units, achieving statistical significance versus placebo (P = .034). These data are not significantly different from those of the main trial. Mean values were ANOVA-adjusted for country and treatment-group interactions. Similarly, the Erosion Joint Count in placebo patients worsened by an average of 2.64, whereas those receiving 30, 75, or 150 mg/d of IL-1ra worsened by 1.46, 1.05, and 1.70, respectively. The overall therapy and 75 mg/d arm achieved significance versus placebo (P = .002 and P < or = .001, respectively). Preliminary data from the extension study indicate continuing benefit. CONCLUSIONS: Treatment with IL-1ra reduced the rate of joint deterioration and development of new bone erosions.

Kirwan J, Byron M, Watt I. · Rheumatology Unit, University of Bristol Division of Medicine, Bristol, UK. · Rheumatology (Oxford). · Pubmed #11285377 links to  free full text

Abstract: OBJECTIVES: To test the hypotheses that the progression of joint space narrowing behaves differently from the progression of erosions and that clinically and radiologically assessed soft tissue swelling relates more to diffuse cartilage loss than to erosive damage. METHODS: Radiographs and clinical data were obtained from 28 patients in a prospective, multicentre, randomized, placebo-controlled trial of prednisolone 7.5 mg daily over 2 yr. Radiographic scoring included the Larsen score, joint space narrowing and soft tissue swelling. Clinical joint inflammation in the hands was assessed every 3 months and cumulative synovitis score over the period of study was then calculated for each joint. The placebo-treated patients and the prednisolone-treated patients were analysed separately. The Larsen scores were compared after log transformation [transformed score=log(10) (original score+1)]. Changes in Larsen scores and joint space narrowing scores were compared with the cumulative presence of clinical synovitis and radiological soft tissue swelling using the correlation coefficient. RESULTS: There was a difference in the rate of progression in the Larsen score between placebo- and prednisolone-treated patients, but there was no significant difference in the rate of joint space loss. In placebo-treated patients, measures of synovitis correlated more strongly with progression of joint space narrowing than with changes in the Larsen score. In prednisolone-treated patients there was no correlation between clinical synovitis and change in Larsen score (r=0.029) and only a slight and non-significant correlation with joint space narrowing (r=0.127). Radiographic evidence of soft tissue swelling remained correlated with joint space narrowing (r=0.279, P:<0.001) but was not correlated with change in Larsen score (r=-0.113, P:<0.001 for difference between correlations). The correlation between Larsen score progression and joint space narrowing seen in the non-treated patients was completely abolished in the glucocorticoid-treated group (r=-0.003). CONCLUSIONS: The progression of joint space narrowing behaves differently from the progression of erosions. Prednisolone slows (or even stops) the progression of erosions (as assessed by the Larsen score) while making no difference to the progression of cartilage loss (as assessed by joint space narrowing). The results also suggest that synovitis, whether measured clinically or radiologically, is more closely related to diffuse cartilage loss than to erosion progression. Any link between synovitis and erosions is abolished by glucocorticoid therapy while the link between synovitis and cartilage loss is not, pointing to at least two different mechanisms for these observed radiological features.

Jiang Y, Genant HK, Watt I, Cobby M, Bresnihan B, Aitchison R, McCabe D. · University of California, San Francisco 94143-0628, USA. · Arthritis Rheum. · Pubmed #10817552 links to  free full text

Abstract: OBJECTIVE: To evaluate radiographic progression and the relationship of radiologic scores obtained by the Genant and Larsen methods in a clinical trial of recombinant human interleukin-1 receptor antagonist (IL-1Ra). METHODS: Patients with rheumatoid arthritis (RA) were randomized into 4 groups: placebo (n = 121) or IL-1Ra at a daily dosage of 30 mg (n = 119), 75 mg (n = 116), or 150 mg (n = 116). Hand radiographs obtained at baseline, 24 weeks, and 48 weeks were scored using both methods. RESULTS: At 24 weeks, by the Genant method, there was significant reduction in the score for progression of joint space narrowing (JSN) and the total score (a combination of erosion and JSN) in all treatment groups. Least-squares mean changes in the Genant erosion score from baseline to 24 weeks were significantly reduced after treatment with IL-1Ra at 30 mg/day and for all IL-1Ra treatment groups combined. The changes corresponded to a reduction of 38% in erosion, 58% in JSN, and 47% in total score. Patients treated with IL-1Ra at 75 mg/day had a significant reduction in the Larsen erosive joint count (LEJC), and all IL-1RA-treated groups combined showed a 45% reduction. Correlations (r) between the Genant total and Larsen scores were 0.84 at baseline, 0.83 at week 24, and 0.83 at week 48 (P < 0.0001); correlations between the Genant erosion score and the LEJC were 0.83 (P < 0.0001) at all visits; correlations between the Genant total and the Larsen scores were 0.32 and 0.49 (P < 0.0001) for progression from baseline to week 24 and from baseline to week 48, respectively; correlations between the Genant erosion score and the LEJC were 0.36 and 0.41 (P < 0.0001) for progression to weeks 24 and 48, respectively. CONCLUSION: IL-1Ra reduced radiologic progression of RA. Scores by the 2 methods correlated strongly for each individual time point, but much less strongly for assessments of disease progression.

Gandy SJ, Brett AD, Dieppe PA, Keen MC, Maciewicz RA, Taylor CJ, Waterton JC, Watt I. · Department of Medical Physics & Bioengineering, Bristol General Hospital, Guinea Street, Bristol BS1 6SY, UK. · Br J Radiol. · Pubmed #15673528 links to  free full text

Abstract: MRI is a valuable imaging modality for assessment of the articular cartilage in rheumatoid arthritis (RA) and is potentially of use in monitoring disease progression and response to therapy. In this study, we investigated the sources of error in volume measurements obtained by segmentation of MR images of knee cartilage in patients with RA and followed cartilage volume in a group of RA patients for 12 months. 23 RA patient volunteers were recruited for knee imaging. Six subjects were imaged at baseline only, six were imaged at baseline and again within an hour in the same imaging session, six subjects were imaged at baseline and 7 days, and 17 subjects were imaged at baseline, 4+/-2 months and 12 months. Imaging was performed at 1.0 T using a three-dimensional spoiled gradient-echo sequence with fat-suppression. Manual image segmentation was performed once or twice on the lateral tibial, medial tibial, patellar and femoral compartment by either one or two segmenters. Coefficients of variation (CoV) for repeated volume measurement of total cartilage were 2.2% (same segmenter, same scan), 5.2% (different segmenter, same scan), 4.9% (same segmenter, different scan, same session), and 4.4% (same segmenter, different scan, different session). Over the 12 month duration of the study there was no significant change in total cartilage volume, nor were there significant changes in volume in any individual compartment. This measurement technique is reproducible, but any net change in cartilage volume over 1 year is very small.