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Focus on rheumatology research

Antibodies blood test could predict the risk of arthritis

Researchers have found a marker that can indicate a person’s likelihood of suffering from rheumatoid arthritis (RA), even 16 years before the condition manifests itself.

A team from the Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), UK, has found that a blood test that examines antibodies that recognise the protein tenascin-C could reliably show those who will contract the condition.

When inflammation occurs in the body, certain proteins are altered through the process of citrullination.

These altered forms can prompt an immune response from the body, which can see it turning antibodies on itself, which causes RA.

Tests that spot antibodies to citrullinated proteins are already used to diagnose the disease. While tests for individual proteins usually have a relatively low diagnostic sensitivity, a more general test called CCP, which detects a synthetic citrullinated peptide, identifies significantly more RA cases.

Lead researcher Dr Anja Schwenzer said: “We knew that tenascin-C is found at high levels in the joints of people with RA. We decided to see if it could be citrullinated and, if so, whether it was a target for the autoantibodies that attack the body in RA.

That might also indicate whether it could be used in tests to indicate the disease.

“When we looked at results from more than 2,000 patients, we found that testing for antibodies that target citrullinated tenascin-C (cTNC) could diagnose RA in around 50 per cent of cases, including some cases not identified by CCP. It also has a very low rate of false positives — it is 98 per cent accurate at ruling out RA.”

The Kennedy Institute’s Prof Kim Midwood said: “What is particularly exciting is that when we looked at samples taken from people before their arthritis began, we could see these antibodies to cTNC up to 16 years before the disease occurred — on average, the antibodies could be found seven years before the disease appeared.

“This discovery therefore gives us an additional test that can be used to increase the accuracy of the CCP assay and that can predict RA, enabling us to monitor people and spot the disease early. This early detection is key because early treatment is more effective.”

Risk of interstitial lung disease not increased

A new study has found no significant difference in the risk of interstitial lung disease (ILD) incidence between patients exposed to tocilizumab, rituximab, or abatacept compared with anti-TNFα therapies.

According to Curtis et al, ILD is a common extra-articular condition in RA, but few studies have systematically investigated its incidence and risk factors in patients receiving anti-tumour necrosis factor-alpha (anti-TNFα) agents or alternate mechanisms of action (MOAs) (eg, T-cell, B-cell, and interleukin-6 inhibitors).

The authors identified 13,795 episodes of biologic exposure in 11,219 patients.

Unadjusted ILD incidence rates (95 per cent confidence interval, or CI) ranged from 4.0 (1.6-8.2, abatacept) to 12.2 (5.6-23.2, infliximab) per 1,000 person-years. Being older (hazard ratio (HR) 3.5; 95 per cent CI 2.1–6.0), being male (HR 3.1; 95 per cent CI 1.2–8.4), and having another pulmonary condition (HR 4.8; 95 per cent CI 1.7–13.7) were associated with increased ILD incidence in either sensitive and/or specific models.

There were no significant differences by biologic class and recent methotrexate exposure was associated with reduced ILD hospitalisation (HR 0.16; 95 per cent CI 0.06-0.46).

“Study findings confirmed that, in a real-world setting, there were significant baseline differences in patients exposed to alternate MOA as compared with patients exposed to anti-TNFs,” according to the authors.

“Patients likely cycle between anti-TNFs before being given the therapeutic option of tocilizumab, rituximab, or abatacept. As a result, patients exposed to alternate MOA may have greater disease severity and duration. Physician perceptions may also play a role in channelling patients to and away from these newer therapies.

“Using data derived from administrative claims may not fully adjust for these differences, and any bias resulting from incomplete adjustment for confounding will bias the results in favour of anti-TNF therapies.”

The study was published in Arthritis Research and Therapy.

PDUS effective in early diagnosis of RA

Quantitative vascular imaging by power Doppler US (PDUS) has clinical utility in predicting which patients will derive benefit from early use of biologic therapy for those with seropositive early RA, according to a new study.

PDUS enables detection of low-velocity blood flow in inflamed small joints of the hands and shows significant correlation to endothelial cell density on synovial histology, permitting reliable assessment of joint inflammation with superior sensitivity to clinical examination.

The objective of the study was to assess the value of quantitative vascular imaging by PDUS as a tool that can be used to stratify patient risk of joint damage in early seropositive RA while still biologic naive but on synthetic DMARD treatment.

A total of 85 patients with seropositive RA of less than three years’ duration had clinical, laboratory and imaging assessments at zero and 12 months.

Imaging assessments consisted of radiographs of the hands and feet, two-dimensional (2D) high-frequency and PDUS imaging of 10 MCP joints that were scored for erosions and vascularity and three-dimensional (3D) PDUS of MCP joints and wrists that were scored for vascularity.

Severe deterioration on radiographs and ultrasonography was seen in 45 and 28 per cent of patients, respectively.

The 3D power Doppler volume and 2D vascularity scores were the most useful US predictors of deterioration.

“Our analysis suggests that 3D power Doppler volume predicts radiographic progression in RA and has the potential to be used, in conjunction with demographic data, to inform decisions on whether anti-TNF treatment should be deployed immediately,” according to the study authors.

“…. While vascular signal seen on ultrasound has previously been described to predict which patients would remain on anti-TNF therapy after one year, this is the first time that it has found clinical utility in predicting which patients would derive clinical benefit from the early use of biologic therapy.”

The study was published in the journal Rheumatology.

Adalimumab improves visual functioning in patients with non-infectious non-anterior uveitis

A new study has found that treatment with adalimumab is associated with statistically significant improvements in visual functioning for subjects with active, non-infectious, non-anterior uveitis.

The purpose of the study by Shepard et al was to compare the effects of adalimumab and placebo on the National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25) in subjects requiring high-dose corticosteroids for active non-infectious intermediate-, posterior-, or pan-uveitis.

The VFQ-25 is a validated measure for assessing the impact of visual impairment from the patient’s perspective.

The VFQ-25 total score is calculated as the mean of 11 vision-related domains and scores ranging from zero (worst vision functioning) to 100 (best vision functioning).

For the study, which was called the VISUAL-1 clinical trial, a total of 217 subjects (110 adalimumab, 107 placebo) were enrolled.

The mean VFQ-25 total scores for adalimumab and placebo are similar through the tapering period but subsequently diverge and maintain separation through week 80.

The average change in VFQ-25 total score from best state achieved prior to week six to the final/early termination visit was -5.50 for placebo and -1.30 for adalimumab.

This corresponds to a statistically significant and clinically meaningful increase of 4.20 (95 per cent confidence interval [CI]: 1.02 – 7.38; P = 0.010) associated with adalimumab relative to placebo.

The longitudinal model estimated a statistically significant treatment effect of adalimumab of 3.07 (95 per cent CI: 2.09 – 4.06; P<0.001).

Cost-effectiveness of developing clinical guidelines should be examined

A recent editorial in the journal Rheumatology has questioned whether the development of clinical guidelines represents good value for money.

According to Colebatch-Bourn et al, while it is not always easy to tell if guidelines lead to improvements in the quality of patient care, some examples do exist.

The British Society for Rheumatology guidelines for the management of early RA, published in 2006, appear to have been associated with a step-up in the prescription of methotrexate (MTX) in the first year after diagnosis.

Conversely, failure to adhere to the EULAR treatment guidelines for early arthritis was associated with an increased risk of radiographic progression and functional impairment.

The authors state that while high-quality guidelines appear to improve quality of care, the true value of any guideline is difficult to quantify precisely.

“The process of guideline development consumes large amounts of resources that can be measured in time given by experts, assembling the required clinical expertise, clinical fellows, task force meetings, time taken to go through the rigorous process involved and the necessary financial support by rheumatology organisations,” according to the article.

“It might make an interesting project to accurately determine the true cost of this.”

The article states that the numbers and quality of clinical guidelines has increased in recent years, which has partly been driven by the presence of standard operating procedures (SOPs) and by an increased body of experience in the methodology used.

“Guidelines need to be adapted to complicated clinical situations and for this reason cannot be too rigid,” according to the authors.

“However, there is some evidence that guidelines can lead to improvements in the quality of care and that failure to comply can be associated with poorer outcomes. Preventing clinicians from being overwhelmed by too many guidelines could be achieved by greater focus on those that are the most important to them, and by identifying common themes between guidelines to produce generic stems and approaches. These steps are likely to improve adoption and adherence to guidelines, which will in turn help to maximise value for money.”

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