Helen I. Keen

Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped?

Objectives Combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockade has increased remission rates in patients with rheumatoid arthritis. However, there are no guidelines regarding cessation of therapy. There is a need for markers predictive of sustained remission following cessation of TNF blocker therapy. Methods Patients in remission (DAS28 <2.6) treated with a TNF blocker and MTX as initial or delayed therapy were recruited. Joints were assessed for grey scale synovitis and power Doppler (PD) activity. Immunological assessment involved advanced six-colour flow cytometry. Results Of the 47 patients recruited, 27 had received initial treatment and 20 delayed treatment with TNF blocking drugs. Two years after stopping TNF blocker therapy, the main predictor of successful cessation was timing of treatment; 59% of patients in the initial treatment group sustained remission compared with 15% in the delayed treatment group (p=0.003). Within the initial treatment group, secondary analysis showed that the only clinical predictor of successful cessation of treatment was shorter symptom duration before receiving treatment (median 5.5 months vs 9 months; p=0.008). No other clinical features were associated with successful cessation of therapy. Thirty-five per cent of patients had low PD activity but levels were not informative. Several immunological parameters were significantly associated with sustained remission including abnormal differentiation subset of T cells and regulatory T cells. Similar non-significant trends were observed in the delayed treatment group. Conclusion In patients in remission with low levels of imaging synovitis receiving combination treatment with a TNF blocker and MTX, immunological parameters and short duration of untreated symptoms were associated with successful cessation of TNF blocker therapy.

An ultrasonographic study of osteoarthritis of the hand: Synovitis and its relationship to structural pathology and symptoms

OBJECTIVE Few studies have examined hand osteoarthritis (OA) pathology using sensitive imaging techniques. The aim of this study was to determine the extent of ultrasound (US)-detected pathology and investigate its relationship with symptoms in hand OA. METHODS Subjects with symptomatic hand OA and controls were recruited. All underwent clinical and US examination of the small joints of both hands and completed a range of measures of hand pain, stiffness, and function. RESULTS Thirty-six subjects with symptomatic OA and 19 control subjects with similar demographics were recruited. US-detected pathology (osteophytes, joint space narrowing, gray-scale synovitis, and power Doppler signal) occurred frequently in symptomatic hand OA (41%, 40%, 46%, and 7% of joints, respectively), and significantly less often in controls (P < 0.001 for all comparisons). Symptomatic joints were more likely to demonstrate US-detected changes of gray-scale synovitis, power Doppler signal, or osteophytes (P < 0.001, P = 0.002, and P < 0.001, respectively). Neither the number of affected joints per individual nor the summative semiquantitative scores for synovitis per individual correlated with symptoms (pain visual analog scale [VAS], global VAS, or Australian/Canadian Osteoarthritis Hand Index). CONCLUSION This study demonstrated extensive synovitis changes as well as the traditional structural radiographic findings of hand OA. Symptomatic joints were significantly more likely to demonstrate US-detected structural changes or inflammation in symptomatic hand OA; however, the extent of changes in individual joints or in individuals did not correlate with the degree of symptoms, which may relate to both the assessment tools and the complex nature of pain.

The development of a preliminary ultrasonographic scoring system for features of hand osteoarthritis

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 κ 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 κ 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.

Can ultrasonography improve on radiographic assessment in osteoarthritis of the hands? A comparison between radiographic and ultrasonographic detected pathology

Objectives: Ultrasonography (US) is used in rheumatology to assess small joints in inflammatory arthritis. Recently there has been some investigation into the utility of US in osteoarthritis (OA), however there has been little comparison of US to other imaging modalities in OA. This study aimed to compare the detection of osteophytosis and joint space narrowing (JSN) by US and conventional radiography (CR) in OA of the hand. Methods: Subjects with OA of the hand underwent US and CR examination of the small joints of both hands to identify osteophytosis and joint space narrowing. Results: 1106 joints of 37 patients were imaged with US and CR. US detected osteophytosis in 448 joints, compared to CR that detected osteophytosis in 228 joints (approximately 30% fewer joints). Where osteophytosis was detected by US but not CR, this was usually proximal to the joint line. Joint space narrowing was detected in 450 joints by US, but only 261 joints by CR. The distribution of US and CR detected osteoarthritis changes in this cohort was consistent with population studies of radiographic hand OA, although metacarpophalangeal (MCP) involvement was higher than might be expected Conclusions: US detected more osteophytosis and joint space narrowing than CR in OA of the hand. Involvement of MCP joints was more common than would be expected from population radiographic studies. The increased detection of OA structural pathology by US may make this a useful tool for hand OA research.

The OMERACT ultrasound task force - Status and perspectives

This article reports the most recent work of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Task Force, and highlights the future research priorities discussed at the OMERACT 10 meeting. Results of the following studies were presented: (1) intra- and interobserver reliability of ultrasound detecting and scoring synovitis in different joints of patients with rheumatoid arthritis (RA); (2) systematic review of previous ultrasound scoring systems of synovitis in RA; (3) enthesitis systematic review and Delphi definition exercise in spondyloarthritis enthesitis; (4) enthesitis intra- and interobserver reliability exercise; and (5) Delphi definition exercise in hand osteoarthritis, and reliability exercises. Study conclusions were discussed, and a future research agenda was approved, notably further validation of an OMERACT ultrasound global synovitis score (GLOSS) in RA, emphasizing the importance of testing feasibility, predictive value, and added value over standard clinical variables. Future research areas will include validating scoring systems for enthesitis and osteoarthritis, and testing the metric qualities of ultrasound for evaluating tenosynovitis and structural damage in RA.

The OMERACT Ultrasound Task Force — Advances and Priorities

This article reports the most recent work of the OMERACT Ultrasound Task Force (post OMERACT 8) and highlights of future research priorities discussed at the OMERACT 9 meeting, Kananaskis, Canada, May 2008. Results of 3 studies were presented: (1) assessing intermachine reliability; (2) applying the scoring system developed in the hand to other joints most commonly affected in rheumatoid arthritis (RA); and (3) assessing interobserver reliability on a deep target joint (shoulder). Results demonstrated good intermachine reliability between multiple examiners, and good applicability of the scoring system for the hand on other joints (including shoulder). Study conclusions were discussed and a future research agenda was generated, notably the further development of a Global OMERACT Sonography Scoring (GLOSS) system in RA, emphasizing the importance of testing feasibility and added value over standard clinical variables. Future disease areas of importance to develop include a scoring system for enthesitis and osteoarthritis.

A systematic review of ultrasonography in osteoarthritis

Background: Ultrasonography has been increasingly utilised to aid the understanding and management of rheumatic conditions. In recent years there has been a focus on the validity and utility of ultrasonography in demonstrating joint pathology, although this has largely focused on inflammatory arthritis. Aims: To undertake a systematic review of the published literature evaluating ultrasonography as an assessment tool in osteoarthritis. Methods: Medline and Pubmed were searched to identify original manuscripts, published before June 2008, utilising ultrasonography to assess the joints of cohorts of subjects with osteoarthritis. Data were extracted from manuscripts meeting the inclusion criteria, with a particular focus on the pathology imaged, the definitions used, scoring systems and their metric properties. Results: Forty-seven studies were identified that utilised ultrasonography to assess structural pathology in osteoarthritis. Doppler function was only assessed in 10 studies and contrast agents in one. There was heterogeneity with regard to the pathology examined, the definition of pathology, quantification and the reporting of these factors. There was also a lack of construct and criterion validity and data demonstrating reliability and sensitivity to change. Conclusions: Whereas there is increasing evidence of the validity of ultrasonography in detecting structural pathology in inflammatory arthritis, more work is required to develop standardised definitions of pathology and to demonstrate the validity of ultrasonography in osteoarthritis.

A systematic review of ultrasonography in gout and asymptomatic hyperuricaemia

Gout is one of the most common inflammatory arthritides. The literature reveals that management of this condition is often suboptimal. Imaging techniques, such as ultrasound (US), may assist in the diagnosis and management of gout and asymptomatic hyperuricaemia (AH). To undertake a systematic review evaluating US as an outcome tool in gout and asymptomatic hyperuricaemia, articles published in Medline and PubMed (1975–February 2012) were identified. Data was extracted and categorised into four different groups namely tophi, articular cartilage, soft tissue pathologies and bony changes, with a focus on validity, responsiveness, reproducibility and feasibility. Lesions reported in the literature include tophi, cartilage abnormalities, soft tissue lesions and erosions. US is able to detect tophi, using MRI as the gold standard, and is sensitive to change. The double contour sign seen overlying cartilage is specific to gout and sensitive to change. Synovial pathology is identified in gout, with some reporting intrasynovial hyperechogeneicity is suggestive of gout. US was less sensitive than MRI to cortical erosions in gout, but better than conventional radiography. Interobserver reliability when assessed ranged from fair to substantial agreement for soft tissue changes and was very good for assessing tophi, double contour and erosions. US is a promising tool which could be used in the diagnosis and management of gout. More studies are needed to assess responsiveness, reliability and feasibility.

Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study)

Objectives In disease modifying antirheumatic drug (DMARD)-naive early rheumatoid arthritis (RA), to compare the efficacy of methotrexate (MTX) and infliximab (IFX) with MTX and intravenous corticosteroid for remission induction. Methods In a 78-week multicentre randomised controlled trial, double-blinded to week 26, 112 treatment-naive RA patients (1987 American College of Rheumatology classification criteria) with disease activity score 44 (DAS44)>2.4 were randomised to MTX + IFX or MTX + single dose intravenous methylprednisolone 250 mg. A treat-to-target approach was used with treatment escalation if DAS44>2.4. In the IFX group, IFX was discontinued for sustained remission (DAS44<1.6 for 6 months). The primary outcome was change in modified total Sharp-van der Heijde score (mTSS) at week 50. Results The mean changes in mTSS score at week 50 in the IFX and intravenous steroid groups were 1.20 units and 2.81 units, respectively (adjusted difference (95% CI) −1.45 (−3.35 to 0.45); p=0.132). Radiographic non-progression (mTSS<2.0) occurred in 81% vs 71% (OR 1.77 (0.56 to 5.61); p=0.328). DAS44 remission was achieved at week 50 in 49% and 36% (OR 2.13 (0.91 to 5.00); p=0.082), and at week 78 in 48% and 50% (OR 1.12 (0.47 to 2.68); p=0.792). Exploratory analyses suggested higher DAS28 remission at week 6 and less ultrasound synovitis at week 50 in the IFX group. Of the IFX group, 25% (14/55) achieved sustained remission and stopped IFX. No substantive differences in adverse events were seen. Conclusions In DMARD-naive early RA patients, initial therapy with MTX+high-dose intravenous steroid resulted in good disease control with little structural damage. MTX+IFX was not statistically superior to MTX+intravenous steroid when combined with a treat-to-target approach.

Double-blind placebo-controlled trial of etanercept in the prevention of work disability in ankylosing spondylitis

Objectives Etanercept has been shown to be rapidly effective in suppressing disease activity in ankylosing spondylitis (AS). The aim of this study was to determine whether etanercept improves work instability as measured by the Ankylosing Spondylitis Work Instability Scale (AS-WIS). Method Forty patients with active AS who were in work but were work unstable were recruited. Patients were randomised to receive 25 mg etanercept or placebo twice weekly for 12 weeks. The primary outcome was change in AS-WIS at week 12. The AS-WIS is a patient-derived outcome measure which allows stratification of the risk of job loss. Secondary outcomes included clinical outcomes and gait parameters. Results The mean improvement in AS-WIS score at week 12 was 2.75 in the etanercept group and 0.68 in the placebo group (p=0.125). The risk of job loss decreased for 11 (55%) of the etanercept group compared with 7 (35%) in the placebo group. Conversely, the risk of job loss increased in 3 (15%) of the placebo group compared with 1 (5%) in the etanercept group. There was no statistically significant difference between treatment groups in change in WIS categories (Mann–Whitney U test=0.153, p=0.160). Significant improvement with etanercept was seen at week 12 in clinical outcomes and gait parameters. Etanercept was well tolerated, with no dropouts due to adverse events. Conclusion This small study confirms the efficacy of etanercept on clinical outcome measures in patients with AS and suggests an effect on work instability which needs to be replicated in a larger controlled study.