Efficacy, General Safety, and Joint Safety of Tanezumab in Japanese Patients with Osteoarthritis: Subgroup Analyses from Two Randomized, Phase 3 Studies

Abstract

Introduction: Tanezumab is a monoclonal antibody against nerve growth factor that is under investigation for the treatment of osteoarthritis (OA) pain. We conducted subgroup analyses of two randomized phase 3 studies to summarize efficacy, general safety, and adjudicated joint safety of tanezumab in Japanese patients with moderate-to-severe OA.

Methods: In Study 1 (NCT02528188), patients received subcutaneous tanezumab 2.5 mg or 5 mg every 8 weeks or daily oral nonsteroidal anti-inflammatory drugs (NSAID) for 56 weeks. The co-primary efficacy endpoints were change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale score and WOMAC Physical Function subscale score at Week 16 (overall study and Japan-specific endpoints) as well as Patient Global Assessment (PGA)-OA score at Week 16 (overall study endpoint only). In Study 2 (NCT02709486), patients received subcutaneous tanezumab 2.5 mg, 5 mg, or placebo every 8 weeks for 24 weeks. Safety monitoring included adjudicated composite joint safety endpoint (CJSE) including rapidly progressive osteoarthritis type 1 (RPOA1), RPOA2, primary osteonecrosis, pathological fracture, or subchondral insufficiency fracture.

Results: For Study 1, Japanese patients (n = 200) treated with tanezumab 2.5 mg and 5 mg showed numerically greater improvements in WOMAC Pain, WOMAC Physical Function, and PGA-OA scores versus NSAID at Week 16. Incidences of treatment-emergent adverse events were generally similar between tanezumab 2.5 mg, 5 mg, and NSAID groups. In the integrated safety analysis (Studies 1 + 2; n = 306), ten patients were adjudicated to have a component of CJSE: RPOA1 [tanezumab 2.5 mg (n = 2), tanezumab 5 mg (n = 5)], RPOA2 [tanezumab 2.5 mg (n = 1), tanezumab 5 mg (n = 1)], or primary osteonecrosis [tanezumab 2.5 mg (n = 1)]. Time-adjusted adjudicated rates of RPOA1 and RPOA2 were higher with tanezumab than NSAID or placebo and increased with dose of tanezumab.

Conclusion: Observations from the Japanese subgroup were generally consistent with the overall study populations.

Keywords: Joint safety; Osteoarthritis; PGA-OA; Pain measurement; Rapidly progressive osteoarthritis; Tanezumab; Treatment outcome; WOMAC pain and physical function.

Fig. 1

Patient disposition. a Japanese patients enrolled in Study 1. b Japanese patients in the pooled safety population. ^a Completed study: patients who completed the planned safety follow-up period. ^b Discontinued study: patients who did not enter or discontinued the planned safety follow-up period, either completed or discontinued the planned treatment period. ^c Only Japanese patients in Study 1 were included in the efficacy and general safety analysis. Efficacy and general safety results of the Japanese patients in Study 2 have been published previously [23]. ^d Adjudicated joint safety outcomes were reported for Japanese patients in both Study 1 and Study 2. NSAID nonsteroidal anti-inflammatory drug