3 OA Studies: ZILRETTA Superior to Off the Shelf Steroids

Three new studies of a novel treatment for osteoarthritis (OA) knee pain (ZILRETTA) report that the injection provided effective pain relief and health-related quality of life that exceeded that of intra-articular corticosteroid injections.

According to the company, Flexion Therapeutics, Inc., one of the studies, which had enrolled 586 patients with knee OA, compared the duration of the analgesic effects in 159 patients who had received prior intra-articular corticosteroid (IACS) treatment and 427 patients who had no previous treatment with IACS. “The results suggest ZILRETTA may provide extended analgesic benefit effect when utilized as the initial intra-articular treatment in patients with knee OA.”

Another study looked at data from three randomized Phase 2/3 trials of ZILRETTA and found that changes in Health Utilities Index Mark 3 (HUI-3) values, a validated measure of health-related quality of life (HRQoL), following ZILRETTA in knee OA patients “exceeded important clinical differences…”

Finally, a THIRD study found that “…ZILRETTA demonstrated significant improvement compared with placebo but not active comparator as measured by average daily pain (ADP). However, when assessed using the WOMAC-A instrument, ZILRETTA demonstrated significant improvement over both PBO and triamcinolone acetonide crystalline suspension (a well-known intra-articular corticosteroid).”

Asked to elaborate on ZILRETTA’s potential to improve key quality of life measures, Michael Clayman, M.D., president and chief executive officer of Flexion, told OTW, “The HUI-3 index incorporates a variety of QoL domains, including ambulation, dexterity and pain, and can be obtained from clinical trial data.”

“The analysis presented at AAOS looked at HUI-3 scores in patients who had participated in Phase 2 or Phase 3 trials of ZILRETTA and compared those scores with HUI-3 scores from individuals in the same age range from the general U.S. population.”

“Before treatment with ZILRETTA, patients with knee OA had lower HUI-3 scores compared with the general population, indicating a lower HRQoL.”

“For the patients included in this analysis, HUI-3 scores improved over the course of the study. This is important in and of itself because it demonstrates that ZILRETTA may improve the QoL of patients with knee OA.”

“In addition, by the end of the treatment studies, HUI-3 scores for the patients analyzed were within 80% of the value of the scores for individuals in the general population. This demonstrates that not only does ZILRETTA improve QoL as assessed by HUI-3, it actually restores QoL to levels that are close to what is seen in the general population.”

“These data suggest that ZILRETTA may help patients with osteoarthritis of the knee obtain the same QoL that they would have in the absence of knee OA.”

Dr. Clayman also told OTW, “In the Phase 3 trial of ZILRETTA we observed that these two tools (WOMAC-A and ADP) yielded different results with respect to the efficacy of ZILRETTA compared to other treatments.”

“In this trial, ADP was sufficiently sensitive to discerning differences between ZILRETTA and saline-placebo but had inadequate sensitivity to discern between ZILRETTA and an active comparator (TAcs).”

“In contrast, we found that WOMAC-A was more sensitive and able to discern differences between the two active treatments.”

“We found that a number of trial and instrument characteristics, including an enriched population using baseline ADP; differences in the scale and scoring of the two tools, the frequency with which response is assessed with each tool and the variability within and between the tools must be considered when using these tools to measure analgesic benefit provided by two active treatments.”