Background Selecting an appropriate primary efficacy criterion is of key importance in the design of a randomized controlled trial (RCT) evaluating therapeutic interventions in knee OA. One may choose among various possible primary efficacy criteria which can be classified as 1/ continuous variables such as pain (on a visual analog scale (VAS)) or function by one of the OA-specific available instruments (providing a numeric variation on a scale indicating the amount of therapeutic effect, which clinical relevance has to be established), or 2/ binary global response criteria, such as the OMERACT-OARSI (1), or response criteria based on the Patient Acceptable Symptom State (PASS) or the Minimum Clinical Important Improvement (MCII) applied to pain, function, or patient global assessment (PGA) (2), which results are expressed in % of responders (yes/no). The sensitivity of these global response instruments has not been compared yet.
Objectives The aim of this study was to compare responder's rates using various definitions of response in a knee OA trial of IAHA, and to identify factors associated with a better response.
Methods Data obtained from a RCT comparing one single IA injection of 40 mg/2.0ml non-chemically modified HA with 48 mg/6.0ml hylan G-F20 were used for this post hoc analysis (3). As non-inferiority of the non-crosslinked HA was demonstrated over 6 months, data of both treatment groups were pooled (280 patients in the full analysis set, 266 completers). Uni- and multivariate stepwise regression analyses were performed to compare response criteria and identify potential factors associated with the best clinical response. OMERACT-OARSI responder criteria were compared to the PASS (≤40 mm) and MCII (≥15 mm improvement) responder criteria calculated for the following outcomes: pain using WOMAC A1 0–100mmVAS format, physical function using WOMAC C (VAS format) and the 0–100 normalized Lequesne index, and PGA on a 0–100 mmVAS.
Results The three most sensitive response instruments were the MCII (relative) for pain, followed by the OMERACT-OARSI responder criteria and the MCII (absolute) for pain with around 80% responders (Fig1). Factors associated with a better response were: a higher pain at baseline (OR [95%CI]: 1.05 [1.02; 1.08]), a shorter delay since diagnosis of knee OA (0.93 [0.88; 0.99]), bilateral knee OA (2.51 [1.11; 5.68], and a better PGA (i.e. a lower score; 0.95 [0.92; 0.98]).
Conclusions In this post-hoc analysis, comparing for the first time several definitions of therapeutic response in a clinical trial of IAHA in knee OA, MCII for pain and OMERACT-OARSI criteria seemed to be the most responsive outcome criteria. Response rates were higher in patients presenting with more pain at baseline, a shorter duration since diagnosis, bilateral knee OA and a better PGA.
Pham T et al. Osteoarthritis Cartilage 2004;12:389–99
Tubach F et al. Arthritis Care Res 2012;64:1699–707
Dreiser RL et al. Ann Rheum Dis 2015;74(Suppl 2):376. Abstract no THU0488.
Acknowledgement We thank TRB Chemedica, for providing access to their trial Database.
Disclosure of Interest E. MAHEU Grant/research support from: TRB Chemedica, L. DREISER Grant/research support from: TRB Chemedica, B. AVOUAC Grant/research support from: TRB Chemedica, T. BARDIN Grant/research support from: TRB Chemedica