Effect Of Triamcinolone Acetonide Extended-release On Synovial Inflammation In Patients With Osteoarthritis Of The Knee

Abstract

PURPOSE: Synovitis is common in osteoarthritis of the knee (OAK) and is associated with pain and disease severity. This open-label phase 3b study is evaluating the effect of an intra-articular (IA) injection of triamcinolone acetonide extended release (TA-ER) on synovial tissue volume (STV), pain, and function (NCT03529942). A prespecified analysis of the primary endpoint is reported. METHODS: STV was determined using gadolinium MRI; synovitis was defined as pre-treatment STV ≥3000 mm3 (3 mL). All patients (pts) received TA-ER 32 mg at baseline (BL) and were assessed at Weeks 6, 12, 18, and 24. MRIs were repeated at Weeks 6 and 24. Interim analysis was performed for the primary efficacy endpoint, mean standardized change from BL in STV at 6 weeks. Planned enrollment was based on earlier studies. RESULTS: We enrolled 116 OAK pts with typical OA characteristics (Table); 89 (77%) demonstrated synovitis at BL. STV was significantly reduced from BL at 6 weeks (P<0.001; Fig. 1A). The primary endpoint was met: standardized least squares mean change in STV was −1.13 (95% CI, −1.35 to −0.91; P<0.001). Western Ontario and McMaster Universities Osteoarthritis Index (pain) was significantly reduced at 6 weeks in all pts (Fig. 1B). 24 (20.7%) pts experienced ≥1 treatment-emergent adverse event (TEAE); 6 (5.2%) pts had ≥1 index-knee TEAE. All TEAEs were mild or moderate; none were treatment related. CONCLUSIONS: At 6 weeks, a single TA-ER IA injection markedly reduced STV in pts with synovitis at BL. Marked symptomatic improvement was observed in all pts at 6 weeks following TA-ER.