Background/Purpose: Inflammation is a key contributor to osteoarthritis (OA).¹ OA pain is mediated by interactions between inflammatory cytokines and other features including local tissue damage, synovitis and cellular response mechanisms.¹ Synovitis is integral to OA, and is associated with symptom severity, joint dysfunction and cartilage loss.² FX006, an extended-release formulation of triamcinolone acetonide (TA) for intra-articular (IA) injection, provided statistically and clinically significant, sustained improvements in pain/stiffness/function of knee OA vs placebo in clinical trials.³ We compared FX006 efficacy in patients with and without baseline inflammation determined by clinical assessment.

Methods: A pooled subgroup analysis of 3 double-blind, randomized, placebo-controlled trials (NCT01487161/NCT02116972/NCT02357459) was conducted. Patients with Kellgren-Lawrence grade 2/3 knee OA and Average Daily Pain (ADP)-intensity score ≥5–≤9 (0–10 Numerical Rating Scale) received a single IA injection of FX006 40 mg or saline-placebo. Investigators assessed index knees for clinical indicators of inflammation (effusion, Baker’s cyst, tenderness, swelling, and/or redness/heat). ADP-intensity was assessed daily for 24 weeks. Western Ontario and McMaster University Arthritis Index for OA (WOMAC; 0–4 Likert scale) pain (A), stiffness (B), and physical function (C) were assessed at baseline and Weeks 4/8/12.

Results: 349/586 patients (60%) had baseline clinical inflammation (Table). Changes from baseline in weekly mean ADP-intensity and WOMAC-A, B, C consistently favored FX006 vs saline-placebo (Figure). FX006 effect was enhanced, generally >2-fold, in patients with vs without baseline clinical inflammation: least squares mean differences for ADP and WOMAC-A, B, C, respectively, was –1.84 vs –0.74, –0.71 vs –0.27, -0.82 vs -0.41, and -0.69 vs -0.26 at Week 8, and –1.35 vs –0.37, –0.44 vs –0.16, -0.50 vs -0.27, and -0.44 vs -0.16 at Week 12.

Conclusion: FX006 provided sustained clinical improvement in knee OA vs saline-placebo irrespective of baseline clinical inflammation. Enhanced FX006 effect in patients with baseline clinical inflammation is consistent with the role of inflammation in OA pathogenesis and known anti-inflammatory action of TA. A drawback of this study is the lack of standardized measures of inflammation. Longer-term evaluations with objective inflammation measures (e.g., ultrasound, biomarkers) are needed.

¹Robinson WH, et al. Nat Rev Rheumatol. 2016;12:580-92.

²Sellam J. Nat Rev Rheumatol. 2010;6(11):625-35.

³Conaghan P, et al. Osteoarthr Cartil. 2017;25:S432-S433.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effectiveness-of-fx006-intra-articular-injection-in-patients-with-knee-osteoarthritis-who-present-with-and-without-clinical-inflammation-at-baseline-a-pooled-analysis-of-data-from-3-double-blind-ran/