Background/Purpose: In a Phase 3 randomized controlled study, differing efficacy results were observed when triamcinolone acetonide extended-release (TA-ER) was compared to conventional TA crystalline suspension (TAcs) with two different pain measures, average daily pain (ADP) using a 0-10 numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A subscale). Trial enrollment criteria may have contributed to this discrepancy, as a moderate-to-severe ADP score of ≥5 to ≤9 was required at baseline whereas no limitations were placed on baseline WOMAC-A score (0-4 Likert). This allowed for randomization of patients who reported their knee pain as mild via WOMAC-A criteria. This post hoc analysis assessed treatment effects in those patients who reported moderate-to-severe OA pain prior to treatment on both ADP and WOMAC-A scales.

Methods: This post hoc analysis included adults (≥40 years) with knee OA (Kellgren-Lawrence Grade 2-3) who reported moderate-to-severe knee OA pain at baseline using both instruments (ADP ≥5 to ≤9 and WOMAC-A ≥2) from a Phase 3 randomized controlled study (concordant pain reporters; n=292). Patients received a single intra-articular injection of TA-ER 32 mg (n=95), TAcs 40 mg (n=100), or Saline-placebo (n=97). Patient-reported ADP‐intensity (including area under the effect [AUE] curves), WOMAC-A (pain), WOMAC-B (stiffness), WOMAC-C (function), Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QoL), rescue medication use, Patient Global Impression of Change (PGIC), and adverse events (AEs) were assessed throughout the study.

Results: Baseline characteristics (Table 1) and AE profiles were consistent with the full analysis population. TA-ER significantly (P < 0.05) improved ADP scores compared with TAcs (Weeks 5-19) and Saline-placebo (Weeks 1-20) (Figure 1). AUE_Weeks1–12 and AUE_Weeks1–24 were statistically significantly greater for TA-ER compared with TAcs (-47.7 [-94.4, -1.0] and -98.4 [-194.5, -2.3], respectively; P < 0.05 for both) and Saline-placebo (-136.1 [-184.2, -88.0] and -212.1 [-311.1, -113.1], respectively; P < 0.0001 for both). At Week 12, the proportion of patients who reported they had no knee pain (ADP score=0) was greater with TA-ER (~28%) compared with TAcs (~8%) (Figure 2); ~20% of patients who received TA-ER still reported no knee pain at Week 16. TA-ER significantly (P < 0.05) improved WOMAC-A, -B, -C, KOOS-QoL, rescue medication use, and PGIC compared with TAcs and Saline-placebo through at least Weeks 4-12.

Conclusion: In patients with knee OA who reported concordant moderate-to-severe pain at baseline across two different reporting instruments, TA-ER provided statistically significant and clinically meaningful pain relief for ≥16 weeks compared with conventional TAcs and Saline-placebo, and also improved stiffness, function, and QoL. Concordant pain reporters were better able to discern treatment effect; results of this post hoc analysis have implications for study design and patient recruitment of future trials evaluating efficacy of analgesics.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/concordance-of-baseline-pain-measures-across-two-reporting-instruments-influences-treatment-effect-post-hoc-analysis-of-a-phase-3-randomized-controlled-trial-of-triamcinolone-acetonide-extended-rel/