Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip

Abstract

Purpose: A pooled analysis was conducted to evaluate tanezumab efficacy and safety in patients with osteoarthritis (OA), including subgroup analyses of at-risk patients with diabetes, severe OA symptoms, and those aged ≥65 years.

Patients and methods: Data from phase III placebo-controlled clinical trials of patients with moderate-to-severe OA of the knee or hip were pooled to evaluate tanezumab efficacy (four trials) and safety (nine trials). Patients received intravenous tanezumab, tanezumab plus an oral NSAID (naproxen, celecoxib, or diclofenac), active comparator (naproxen, celecoxib, diclofenac, or oxycodone), or placebo. Efficacy assessments included change from baseline to week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores, Patient's Global Assessment (PGA) of OA, and percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% improvement in WOMAC pain. Safety assessments included adverse event (AE) documentation and physical and neurologic examinations.

Results: Tanezumab significantly improved all efficacy end points in the overall population. Efficacy in at-risk patient subgroups was similar to the overall population. Incidence of AEs was highest in the tanezumab plus NSAID group and lowest in the placebo group. Incidence of AEs in the tanezumab monotherapy and active comparator groups was similar. Overall incidence of AEs was similar across subgroups. AEs of abnormal peripheral sensation were more frequently reported in tanezumab-treated patients compared with placebo or active comparator. Patients receiving active comparator had a slightly higher incidence of AEs suggestive of postganglionic sympathetic dysfunction.

Conclusion: Tanezumab consistently provided significant improvement of pain, physical function, and PGA in individuals with OA, including patients with diabetes, severe OA symptoms, or aged ≥65 years. No increased safety risk was observed in at-risk patient subgroups.

Trial registration: NCT00733902, NCT00744471, NCT00830063, NCT00863304, NCT00809354, NCT00864097, NCT00863772, NCT01089725, NCT00985621.

Keywords: efficacy; nerve growth factor; osteoarthritis; safety; tanezumab.

Conflict of interest statement

Disclosure LT, HN, MTB, and CRW are employees of and hold stock and/or stock options in Pfizer Inc; AEB is currently a speaker and serves on advisory boards for Pfizer Inc; TJS received funding for the ongoing clinical research studies from Pfizer Inc and Regeneron; the authors report no other conflicts of interest in this work.

Figures

Figure 1

Least squares mean change in WOMAC pain (A), WOMAC physical function (B), and Patient’s Global Assessment (C) from baseline to week 16 for the overall population. Notes: *P≤0.05; **P≤0.01; ***P≤0.001 vs placebo. ^P≤0.05; ^^P≤0.01; ^^^P≤0.001 vs naproxen. Abbreviations: BID, twice daily; LS, least squares; PGA, Patient’s Global Assessment; SEM, standard error of the mean; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 2

Least squares mean change in WOMAC pain from baseline to week 16 for the subgroup analyses. Notes: *P≤0.05; **P≤0.01; ***P≤0.001 vs placebo. ^P≤0.05; ^^P≤0.01; ^^^P≤0.001 vs naproxen. Abbreviations: BID, twice daily; LS, least squares; OA, osteoarthritis; SEM, standard error of the mean; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 3

Least squares mean change in WOMAC physical function from baseline to week 16 for the subgroup analyses. Notes: *P≤0.05; **P≤0.01; ***P≤0.001 vs placebo. ^P≤0.05; ^^P≤0.01; ^^^P≤0.001 vs naproxen. Abbreviations: BID, twice daily; LS, least squares; OA, osteoarthritis; SEM, standard error of the mean; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 4

Least squares mean change in PGA from baseline to week 16 for the subgroup analyses. Notes: *P≤0.05; **P≤0.01; ***P≤0.001 vs placebo. ^P≤0.05; ^^P≤0.01; ^^^P≤0.001 vs naproxen. Abbreviations: BID, twice daily; LS, least squares; OA, osteoarthritis; PGA, Patient’s Global Assessment; SEM, standard error of the mean; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 5

Percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% improvement on the WOMAC pain subscale at week 16 (overall group). Notes: **P≤0.01; ***P≤0.001 vs placebo. ^P≤0.05; ^^P≤0.01; ^^^P≤0.001 vs naproxen. Abbreviations: BID, twice daily; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 6

Percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% improvement on the WOMAC pain subscale at week 16 in the subgroups. Notes: *P≤0.05; **P≤0.01; ***P≤0.001 vs placebo. ^P≤0.05; ^^P≤0.01; ^^^P≤0.001 vs naproxen. Abbreviations: BID, twice daily; OA, osteoarthritis; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.