How to effectively utilize imaging in disease-modifying treatments for osteoarthritis clinical trials: the radiologist’s perspective

ABSTRACT

Introduction: One of the reasons for failures of disease-modifying osteoarthritis drug clinical trials has been the radiography-based definition of structural eligibility criteria. Imaging, particularly MRI, has a critical role in planning and conducting clinical trials of osteoarthritis.

Areas covered: A literature search was performed using keywords including ‘osteoarthritis,’ ‘knee,’ ‘MRI,’ ‘intra-articular injection,’ ‘semiquantitative scoring,’ ‘clinical trial,’ and other specific terms where relevant. The core concepts of using MRI in osteoarthritis clinical trials are explained focusing on knee osteoarthritis, including its role in determining patient eligibility and inclusion/exclusion criteria as well as outcome measures from the expert musculoskeletal radiologist’s perspective. A brief overview of statistical analyses that should be deployed in clinical trials utilizing semiquantitative MRI analyses is discussed.

Expert opinion: In order to increase chances to detect measurable efficacy effects, investigators should consider utilizing MRI from screening to outcome assessment. Recognition of several phenotypes of osteoarthritis helps in participant stratification and will lead to more targeted clinical trials. Inclusion and exclusion criteria need to be defined using not only radiography but also MRI. Correct intra-articular injection of investigational compounds is critically important if intra-articular drug delivery is required, and such procedure should be performed and documented using appropriate imaging guidance.

KEYWORDS:

• Clinical trial
• DMOAD
• radiography
• injection
• knee
• MRI
• osteoarthritis

Article highlights

• The choice of MR pulse sequences must be adapted for optimized visualization of the specific pathological feature to be assessed in a clinical trial

• Baseline joint space width (JSW) measurement as a surrogate for cartilage and meniscus integrity is recommended in order to ensure sufficient remaining cartilage, particularly, to detect potential anti-catabolic drug effects on cartilage.

• Structural inclusion and exclusion criteria need to be defined using not only radiography but also MRI, as certain pathologies are radiographically occult and can potentially have detrimental effects on the success of clinical trials and also patient safety.

• MRI-defined structurally normal knees should not be included in clinical trials, particularly, whenever anabolic effects on cartilage are expected.

• To facilitate efficient screening of potential osteoarthritis clinical trial participants, an MRI-based screening tool has been developed, that is, Rapid OsteoArthritis MRI Eligibility Score (ROAMES).

• Technically successful intra-articular injection of investigational compounds is critically important, and such procedure should be performed with appropriate imaging guidance and documentation.

Declaration of interest

A. Guermazi is the President of Boston Imaging Core Lab (BICL), LLC, and a consultant to MerckSerono, AstraZeneca, Pfizer, Galapagos, Roche, and TissueGene. F. Roemer is a shareholder of BICL, LLC, and is a consultant to Calibr – California Institute of Biomedical Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.