A draft set of criteria for the validation of soluble biomarkers reflecting damage endpoints was proposed at OMERACT 8. At OMERACT 9 we aimed to scrutinize the necessity for each of these criteria ...according to the objectives of the working group.
The OMERACT 8 draft criteria and the principle objectives of the validation process were clarified at a meeting of the working group in London, December 2007. A new framework was proposed after the following steps were conducted: (A) A systematic review of the literature focusing on the draft criteria and a preselected group of biomarkers (MMP3, CTX-II, RANKL, OPG, CTX-I) followed by a Delphi consensus exercise addressing the importance of individual criteria and identification of omissions in the draft set. (B) Formal debate as well as group discussion centered on the key arguments for inclusion/exclusion of specific criteria. (C) Onsite interactive electronic voting on the importance of specific criteria. The framework was presented and discussed at OMERACT 9 in both breakout and plenary sessions followed by a vote on its acceptance.
The objectives of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis biomarkers in relation to their predictive validity for damage endpoints was clarified and supported by OMERACT 9 participants. The OMERACT 8 draft validation criteria were reformulated into an essential category focused on criteria addressing the OMERACT Filter elements of discrimination (incorporating truth) and feasibility, and a desirable but nonessential category of other criteria addressing truth. This revised draft set was endorsed by participants at OMERACT 9.
A revised set of validation criteria has been drafted by consensus at OMERACT 9 that focuses on the performance characteristics of biomarker assays, the importance of addressing potential confounders, and the essential requirement for clinical validation studies.
To test the OMERACT 8 draft validation criteria for soluble biomarkers by assessing the strength of literature evidence in support of 5 candidate biomarkers.
A systematic literature search was ...conducted on the 5 soluble biomarkers RANKL, osteoprotegerin (OPG), matrix metalloprotease (MMP-3), urine C-telopeptide of types I and II collagen (U-CTX-I and U CTX-II), focusing on the 14 OMERACT 8 criteria. Two electronic voting exercises were conducted to address: (1) strength of evidence for each biomarker as reflecting structural damage according to each individual criterion and the importance of each individual criterion; (2) overall strength of evidence in support of each of the 5 candidate biomarkers as reflecting structural damage endpoints in rheumatoid arthritis (RA) and identification of omissions to the criteria set.
The search identified 111 articles. The strength of evidence in support of these biomarkers reflecting structural damage was low for all biomarkers and was rated highest for U-CTX-II score of 6.5 (numerical rating scale 0-10). The lowest scores for retention of specific criteria in the draft set went to criteria that refer to the importance of animal studies, correlations with other biomarkers reflecting damage, and an understanding of the metabolism of the biomarker.
Evidence in support of any of the 5 tested biomarkers (MMP-3, CTX-I, CTX-II, OPG, RANKL) was inadequate to allow their substitution for radiographic endpoints in RA. Three of the criteria in the draft criteria set might not be required, but few omissions were identified.
To develop an algorithm for identification of undifferentiated peripheral inflammatory arthritis (UPIA).
An algorithm for identification of UPIA was developed by consensus during a roundtable meeting ...with an expert panel. It was informed by systematic reviews of the literature used to generate 10 recommendations for the investigation and followup of UPIA through the 3e initiative. The final recommendations from the 3e UPIA Initiative were made available to the panel to guide development of the algorithm. The algorithm drew on the clinical experience of the consensus panel and evidence from the literature where available.
In patients presenting with joint swelling a thorough evaluation is required prior to diagnosing UPIA. After excluding trauma, the differential diagnosis should be formulated based on history and physical examination. A minimum set of investigations is suggested for all patients, with additional ones dependent on the most probable differential diagnoses. The diagnosis of UPIA can be made if, following these evaluations, a more specific diagnosis is not reached. Once a diagnosis of UPIA is established, patients should be closely followed as they may progress to a specific diagnosis, remit, or persist as UPIA, and additional investigations may be required over time.
Our algorithm presents a diagnostic approach to identifying UPIA in patients presenting with joint swelling, incorporating the dynamic nature of the condition with the potential to evolve over time.
The management of patients with new-onset rheumatoid arthritis (RA) requires an awareness of the potential issues and needs that are unique to each patient with regards to their perceptions of their ...disease, physical needs and nutritional issues. Arthritis specialists should have a clear approach to the goals of management that are specific to patients with early rheumatoid arthritis (ERA). In this chapter, evidence for the goals and principles of management in the early treatment of RA is discussed. Patient education, the role of self-management, physical therapies, exercise, diet and drug management are addressed. This chapter aims to provide clinicians with a clear understanding of which interventions have supporting evidence and where further research is required. Where evidence for patients with ERA is lacking, evidence from patients with established RA is reviewed.
Adalimumab, a recent addition to the therapeutic armamentarium in rheumatoid arthritis (RA), has been evaluated in patients with early RA. The DE019 study, a double blind randomized placebo ...controlled trial of adalimumab given 20 mg once a week or 40 mg every other week demonstrated both clinical and radiographic efficacy. A subset analysis of patients with early disease revealed that early treatment with adalimumab may be more efficacious than therapy later in the course of disease, particularly with regard to radiographic progression. The findings support early aggressive intervention in RA.
Data has been generated that infliximab may be more effective when initiated earlier in the course of disease. A subset analysis of the Attract trial has demonstrated better efficacy of infliximab in ...reducing joint damage in an early rheumatoid arthritis (RA) population. Recently a randomized double-blind controlled trial revealed that infliximab in combination with methotrexate (MTX) in an early RA population improved signs and symptoms as well as inhibition in radiographic progression compared with patients receiving infliximab or MTX alone. The possibility of withdrawing infliximab after induction of remission with a combination of infliximab and MTX has been shown in a small pilot trial. Taken together, the results support the early use of infliximab in the treatment of patients with moderate to severe disease.
