How to define responders in osteoarthritis

Background:
Osteoarthritis is a clinical syndrome of failure of the joint accompanied by varying degrees of joint pain,
functional limitation, and reduced quality of life due to deterioration of articular cartilage and involvement of
other joint structures.
Scope:
Regulatory agencies require relevant clinical benefit on symptoms and structure modification for registration
of a new therapy as a disease-modifying osteoarthritis drug (DMOAD). An international Working Group of the
European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and
International Osteoporosis Foundation was convened to explore the current burden of osteoarthritis,
review current regulatory guidelines for the conduct of clinical trials, and examine the concept of
responder analyses for improving drug evaluation in osteoarthritis.
Findings:
The ESCEO considers that the major challenges in DMOAD development are the absence of a precise
definition of the disease, particularly in the early stages, and the lack of consensus on how to detect
structural changes and link them to clinically meaningful endpoints. Responder criteria should help identify
progression of disease and be clinically meaningful. The ideal criterion should be sensitive to change over
time and should predict disease progression and outcomes such as joint replacement.
Conclusion:
The ESCEO considers that, for knee osteoarthritis, clinical trial data indicate that radiographic joint space
narrowing40.5mm over 2 or 3 years might be a reliable surrogate measure for total joint replacement.
On-going research using techniques such as magnetic resonance imaging and biochemical markers may
allow the identification of these patients earlier in the disease process