Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period.

Tanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up. This double-blind, randomised, phase III study enrolled adults in Europe and Japan with moderate-to-severe OA who had not responded to or could not tolerate standard-of-care analgesics. Patients were randomised to tanezumab 2.5 mg or 5 mg subcutaneously or matching placebo every 8 weeks (three doses). Co-primary end points were change from baseline to week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and Patient's Global Assessment of OA (PGA-OA). Joint safety and neurological assessments continued throughout the 48-week study. From March 2016 to December 2017, 849 patients were randomised and evaluated (placebo n=282, tanezumab 2.5 mg n=283, tanezumab 5 mg n=284). At week 24, there was a statistically significant improvement from baseline for tanezumab 5 mg compared with placebo for WOMAC Pain (least squares mean difference±SE -0.62±0.18, p=0.0006), WOMAC Physical Function (-0.71±0.17, p<0.0001) and PGA-OA (-0.19±0.07, p=0.0051). For tanezumab 2.5 mg, there was a statistically significant improvement in WOMAC Pain and Physical Function, but not PGA-OA. Rapidly progressive osteoarthritis (RPOA) was observed in 1.4% (4/283) and 2.8% (8/284) of patients in the tanezumab 2.5 mg and tanezumab 5 mg groups, respectively and none receiving placebo. Total joint replacements (TJRs) were similarly distributed across all three treatment groups (6.7%-7.8%). Tanezumab-treated patients experienced more paraesthesia (5 mg) and hypoaesthesia (both doses) than placebo. Tanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumab 2.5 mg only achieved two co-primary end points. RPOA occurred more frequently with tanezumab 5 mg than tanezumab 2.5 mg. TJRs were similarly distributed across all three groups. NCT02709486.

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Competing interests: FB reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, outside the submitted work. FJB reports grants and personal fees from Pfizer, and grants from AbbVie, UCB, Bristol-Meyers Squibb, Roche, Servier, Bioiberica, Sanofi, Grunenthal, GlaxoSmithKline, Lilly, Janssen, Regeneron, Amgen and TRB Chemedica, outside the submitted work. AG reports personal fees from Merck Serono, Pfizer, TissueGene, Roche, Galapagos, AstraZeneca, personal fees from Boston Imaging Core Lab, LLC, outside the submitted work. KM reports personal fees from Merck, Pfizer, Lilly, Ayumi, Mundi Pharma, Janssen, Nippon Zok, outside the submitted work. LV reports personal fees and other from Eli Lilly and Company, outside the submitted work. TY reports personal fees and other from Pfizer outside the submitted work. RJ reports personal fees and other from Pfizer outside the submitted work. WC reports personal fees and other from Pfizer outside the submitted work. MTB reports personal fees and other from Pfizer outside the submitted work, and has a patent pending (Tanezumab Method of Treatment). CRW reports personal fees and other from Pfizer outside the submitted work, and has a patent pending (Tanezumab Method of Treatment). KMV reports personal fees and other from Pfizer outside the submitted work.