Summary of presentation of 3 disease groups: rheumatoid arthritis (RA), spondyloarthritis (SpA), and knee osteoarthritis (OA).
| Disease Group | Measurement Instrument | Unit of Measurement | What are the outcome domains currently covered by the instrument? | Validation Reached | Is the chosen instrument/measure validated enough for being considered an outcome measure and included in a core set of outcomes? | |
|---|---|---|---|---|---|---|
| RA | Radiographs | Joint (hands and feet) | Structural damage (erosion, JSN) | Most of the scoring methods of erosions and JSN have been demonstrated to fulfill all aspects of validity. Can be considered as patient outcome in RCT, observational studies, and in clinical care | Erosion/JSN as combined scoring system has been measured in many RCT and has been considered critical for both evaluating efficacy and guiding evaluation and treatment. It has been demonstrated to be a good prognostic outcome of severity and mortality, and it has been used as a surrogate for patient outcome in observational studies. Therefore it is used also in the context of patient outcome in usual clinical care | |
| MRI | Joint (hand) | Disease activity (synovitis, osteitis) | The RAMRIS scoring method for synovitis/osteitis has been demonstrated to fulfill face, construct, and some aspects of discrimination validity, and to be predictive of future radiographic damage. Feasibility was suggested by its use in multiple large RCT | Synovitis/osteitis good candidate outcome measures: prognostication+++, sensitivity to change+++ | ||
| Structural damage (erosion, JSN) | The RAMRIS scoring method for erosions has been demonstrated to fulfill face, construct, and some aspects of discrimination validity. These data support further evaluation of erosion as candidate outcome measure (surrogate of radiographic structural damage) for future trials. The RAMRIS scoring method for JSN has been demonstrated to fulfill face and construct validity. These data support further evaluation of JSN as candidate outcome measure for future trials | Erosion: Good possible candidate for severity and damage; JSN: Possible candidate for severity and damage | ||||
| Soluble biomarkers | Patient (blood) | Disease activity | CRP has been demonstrated to fulfill all aspects of validity but some aspects of discrimination remain a problem. It is also considered a good indicator for future severity and mortality | This measure has been used in many trials and has been considered critical for both evaluating efficacy and severity | ||
| Damage/severity (ACPA, cleavage products, matrix metalloproteinase 3, calprotectin and receptor agonist of nuclear factor B ligand) | Some biomarkers are clearly related to structural radiographic progression and severity (e.g., ACPA, MMP3) and some have demonstrated change in accordance with radiographic progression (MMP3). However, further validation is needed before using them as candidates outcome measures for future interventional trial | Only prediction of future radiographic damage was demonstrated. Further validation is needed | ||||
| SpA | MRI | Joint (axial-SIJ, spine) | Disease activity (bone marrow edema) | Several scoring methods at SIJ and spine levels have been demonstrated to fulfill face validity and discrimination). Feasibility not widely examined. Noted that MRI is considered to be quite good for diagnostic purposes (i.e., presence of sacroiliitis) | Bone marrow edema as quantified by SPARCC spine and SIJ and Berlin spine MRI scores are excellent candidate outcome measures for disease activity. Not validated for structural damage | |
| Ultrasound | Joint (peripheral enthesis) | Structural damage (bone marrow edema, erosions, fat lesions) Disease activity (synovitis, enthesitis) | Preliminary data for bone marrow edema and fat lesions Detection of synovitis has been demonstrated to be valid but yet sensitive to change in RCT. Detection of enthesitis has been demonstrated to fulfill some aspects of truth and discrimination (including sensitivity to change) but not in RCT. Feasibility remains a problem | Further data needed from longitudinal and interventional studies Possible good candidate, but no data available | ||
| Structural damage (erosions, enthesophytes, calcifications) | Truth aspect demonstrated for erosions and enthesophytes. Sensitivity to change/responsiveness not yet demonstrated. No data available in RCT | No data available | ||||
| Soluble biomarkers | Patient (blood) | Disease activity, systemic inflammation (CRP, IL-6) | CRP has been demonstrated to fulfill face validity, some aspect of construct and discrimination validity, and also to be weakly predictive of future radiographic damage. | CRP usually used in RCT, but lack of representation in all patients with active disease | ||
| Damage/severity (MMP3) | Not enough data available for suggesting extensive use, or being tested in clinical trials | Only prediction of future radiographic damage was demonstrated | ||||
| Knee OA | Radiographs | Joint | Structural damage (JSN, osteophytes) | JSN fulfills all aspects of validity, reliability related to acquisition technique. Noted that JSN in used in clinical decision making | JSN already accepted in core set of OA trials from previous OMERACT recommendations | |
| MRI | Joint | Disease activity (synovitis, effusion) | Synovitis, effusion have criterion, reliability, and responsiveness data, as well as predictive validity for severe progression (knee replacement) | Recommendations from OARSI suggest cartilage measures should be included as a primary outcome measure in structure modification trials. More RCT data required. More data from RCT required on other biomarkers such as bone measures | ||
| Structural damage (cartilage, bone, menisci, ligaments) | Cartilage morphology is the most studied feature and is valid. Bone marrow lesions have criterion and discrimination (reliability and some data on responsiveness) validity and also to be predictive of future structural damage | |||||
| Ultrasound | Joint | Disease activity (synovitis, effusion) | Detection of synovitis and effusion has demonstrated validity but not in RCT. Both detection of synovitis and effusion have been demonstrated for severe progression (knee replacement) | Possible good candidates, but no data available | ||
| Structural damage (cartilage loss, osteophytes) | Validity demonstrated for both cartilage loss (limited anatomical view acknowledged) and osteophytes. No data available as outcomes candidates in RCT | Possible good candidates, but no data available | ||||
JSN: joint space narrowing; RCT: randomized controlled trials; MRI: magnetic resonance imaging; RAMRIS: Rheumatoid Arthritis MRI Score; OARSI: OA Research Society International; SIJ: sacroiliac joint; CRP: C-reactive protein; IL-6: interleukin 6; MMP3: matrix metalloproteinase-3; ACPA: anticitrullinated protein antibodies; SpA: spondyloarthritis; SPARCC: SpondyloArthritis Research Consortium of Canada; OMERACT: Outcome Measures in Rheumatology.