Rescue Analgesic Medication Use by Patients Treated with Triamcinolone Acetonide Extended-Release for Knee Osteoarthritis Pain: Pooled Analysis of Three Phase 2/3 Randomized Clinical Trials

INTRODUCTION: In clinical trials for knee osteoarthritis (OAK), rescue medication is commonly provided to manage uncontrolled index-knee pain. The impact of treatment on rescue medication utilization provides important information on the robustness of analgesic effect. In randomized controlled OAK trials (NCT01487161, NCT02116972, NCT02357459), intra-articular (IA) triamcinolone acetonide extended-release (TA-ER) demonstrated substantial, prolonged analgesia versus saline-placebo and TA crystalline solution (TAcs) as assessed by patient-reported pain scales. This pooled analysis assessed the impact of TA-ER on rescue medication use. METHODS: Patients (N = 798) with OAK (American College of Rheumatology criteria; Kellgren–Lawrence grade 2/3) and baseline average daily pain intensity score ≥ 5 to ≤ 9 (0–10 numeric rating scale) received a single IA injection of TA-ER (N = 324), saline-placebo (N = 262), or TAcs (N = 212). Acetaminophen/paracetamol tablets were provided to treat uncontrolled pain (knee or otherwise). Rescue medication consumption was monitored through a daily diary; pill counts were confirmed at the clinical site. Differences in rescue medication use were measured by least-squares mean (LSM) differences, number of rescue medication tablets used per day, and in area under the effect (AUE) curves of rescue medication tablets used per week. RESULTS: The overall number of rescue medication tablets used per day through week 24 was significantly less (p ≤ 0.05) for TA-ER versus saline-placebo (LSM difference, − 0.43) and TAcs (− 0.24). Rescue medication use was significantly (p ≤ 0.05) lower following TA-ER versus saline-placebo across weeks 1–12 (AUE(weeks1–12); LSM difference, − 24.5) and weeks 1–24 (AUE(weeks1–24); − 51.6) and versus TAcs across weeks 1–12 (AUE(weeks1–12); − 21.1). CONCLUSIONS: In patients with painful OAK, reduced rescue medication use may be a potential benefit of TA-ER and further supports its analgesic efficacy. Additional research is needed to assess whether TA-ER impacts the use of other common oral analgesics (nonsteroidal anti-inflammatory drugs, opioids) for patients with OAK. FUNDING: Flexion Therapeutics, Inc., Burlington, MA, USA. PLAIN LANGUAGE SUMMARY: Plain language summary available for this article.