Background/Purpose: A recent meta-analysis concluded that intra-articular corticosteroids (IACS) for knee osteoarthritis (OA) may be associated with moderate improvement in pain compared with control treatment.^1,2 Notably, evidence quality was graded “low” due in part to inclusion of many small trials and trial heterogeneity.^1,2  Only 3 trials were moderate to large in size (≥50 patients/arm), with a variety of control treatments and pain endpoints. Across those 3 trials, at 1–2 weeks, 4–6 weeks, and 3 months post-treatment, standardized mean difference (SMD) corresponded to numbers needed to treat (NNT) of 8, 15, and infinity (indicating that the benefit of treatment cannot be determined; Figure).² FX006 is an extended-release formulation of triamcinolone acetonide for IA injection. We updated the meta-analysis by including data from two large, randomized, placebo-controlled trials of FX006 in patients with knee OA and heuristically compared the analysis of FX006 to the moderate to large trials to help assess the clinical relevance of FX006.

Methods: In studies FX006-2014-006 (NCT02116972) and FX006-2014-008 (NCT02357459), knee OA patients (Kellgren-Lawrence Grade 2 or 3; Average Daily Pain (ADP)-intensity ≥5–≤9) received a single IA injection of FX006 40 mg (N=104 and N=161, respectively) or saline-placebo (N=104 and N=163, respectively). ADP was collected for 24 weeks post-injection. SMD (95% CI) was computed for ADP-intensity at 2 weeks, 6 weeks, and 3 months post-treatment using least-squares mean (LSM) difference for FX006 from saline-placebo derived from each trial. Weighted-average SMD (95% CI) for FX006 and corresponding NNT for FX006 vs saline-placebo were determined and compared to NNTs reported for IACS.^1,2

Results: FX006 yielded a weighted average SMD (95% CI) of −0.51 (−0.72, −0.31), −0.56 (−0.74, −0.36), and −0.34 (−0.52, −0.14) at 2 weeks, 6 weeks, and 3 months post-treatment, respectively, corresponding to a NNT (95% CI) of 4 (1 to 7), 4 (1 to 6), and 10 (7 to 13) at the corresponding time points (Figure). The magnitude of the FX006 effect is favorable compared with that determined for IACS, with a lower NNT (pooled estimate):  4 vs 8 (1–2 weeks), 4 vs 15 (4–6 weeks), and 10 vs infinity (3 months).

Conclusion: The two large FX006 studies in the expanded analysis demonstrated effective analgesia through 3 months with reduced NNT compared with traditional IACS. Limitations of the heuristic comparison include small sample sizes, trial heterogeneity, non-placebo controls, and other factors among the comparator trials.

¹Juni P, et al. Cochrane Database Syst Rev. 2015;22:CD005328.

²da Costa BR, et al. JAMA. 2016;316:2671-2.