Effect of Tanezumab on Joint Pain, Physical Function, and Patient Global Assessment of Osteoarthritis Among Patients With Osteoarthritis of the Hip or Knee: A Randomized Clinical Trial

Abstract

Importance: Patients with osteoarthritis (OA) may remain symptomatic with traditional OA treatments.

Objective: To assess 2 subcutaneous tanezumab dosing regimens for OA.

Design, setting, and participants: A randomized, double-blind, multicenter trial from January 2016 to May 14, 2018 (last patient visit). Patients enrolled were 18 years or older with hip or knee OA, inadequate response to OA analgesics, and no radiographic evidence of prespecified joint safety conditions.

Interventions: Patients received by subcutaneous administration either tanezumab, 2.5 mg, at day 1 and week 8 (n = 231); tanezumab, 2.5 mg at day 1 and 5 mg at week 8 (ie, tanezumab, 2.5/5 mg; n = 233); or placebo at day 1 and week 8 (n = 232).

Main outcomes and measures: Co-primary end points were change from baseline to week 16 in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain (0-10, no to extreme pain), WOMAC Physical Function (0-10, no to extreme difficulty), and patient global assessment of osteoarthritis (PGA-OA) (1-5, very good to very poor) scores.

Results: Among 698 patients randomized, 696 received 1 or more treatment doses (mean [SD] age, 60.8 [9.6] years; 65.1% women), and 582 (83.6%) completed the trial. From baseline to 16 weeks, mean WOMAC Pain scores decreased from 7.1 to 3.6 in the tanezumab, 2.5 mg, group; 7.3 to 3.6 in the tanezumab, 2.5/5 mg, group; and 7.3 to 4.4 in the placebo group (least squares mean differences [95% CI] vs placebo were -0.60 [-1.07 to -0.13; P = .01] for tanezumab, 2.5 mg, and -0.73 [-1.20 to -0.26; P = .002] for tanezumab, 2.5/5 mg). Mean WOMAC Physical Function scores decreased from 7.2 to 3.7 in the 2.5-mg group, 7.4 to 3.6 in the 2.5/5-mg group, and 7.4 to 4.5 with placebo (differences vs placebo, -0.66 [-1.14 to -0.19; P = .007] for tanezumab, 2.5 mg, and -0.89 [-1.37 to -0.42; P < .001] for tanezumab, 2.5/5 mg). Mean PGA-OA scores decreased from 3.4 to 2.4 in the 2.5-mg group, 3.5 to 2.4 in the 2.5/5-mg group, and 3.5 to 2.7 with placebo (differences vs placebo, -0.22 [-0.39 to -0.05; P = .01] for tanezumab, 2.5 mg, and -0.25 [-0.41 to -0.08; P = .004] for tanezumab, 2.5/5 mg). Rapidly progressive OA occurred only in tanezumab-treated patients (2.5 mg: n = 5, 2.2%; 2.5/5 mg: n = 1, 0.4%). The incidence of total joint replacements was 8 (3.5%), 16 (6.9%), and 4 (1.7%) in the tanezumab, 2.5 mg; tanezumab, 2.5/5 mg; and placebo groups, respectively.

Conclusions and relevance: Among patients with moderate to severe OA of the knee or hip and inadequate response to standard analgesics, tanezumab, compared with placebo, resulted in statistically significant improvements in scores assessing pain and physical function, and in PGA-OA, although the improvements were modest and tanezumab-treated patients had more joint safety events and total joint replacements. Further research is needed to determine the clinical importance of these efficacy and adverse event findings.

Trial registration: ClinicalTrials.gov Identifier: NCT02697773.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Schnitzer reported receiving nonfinancial support from Pfizer during the conduct of the study and grants, personal fees, and nonfinancial support from Pfizer, Regeneron, AbbVie, and Kolon TissueGene; personal fees from Vertex, Sanofi, Astellas, and Calibr; grants and personal fees from Flexion; personal fees and nonfinancial support from GlaxoSmithKline and Aptinyx; and grants from Galapagos and Grunenthal outside the submitted work. Dr Schnitzer also reported performing clinical research for Pfizer Inc and Eli Lilly and Company and has received consulting fees from Pfizer Inc and Eli Lilly and Company. Dr Easton reported receiving compensation for participation in multiple Pfizer-sponsored clinical trials. Dr Pang reported receiving consulting fees from Pfizer Inc. Dr Levinson reported receiving grants from Pfizer during the conduct of the study and grants from Amgen, Regeneron, and AbbVie outside the submitted work. Mr Pixton and Drs Davignon, Brown, Verburg, and West are employees of Pfizer Inc and own stock. Dr Viktrup is an employee of Eli Lilly and Company. Drs Brown and West reported having tanezumab method of treatment patents pending. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

aTwo randomized patients did not meet eligibility criteria and therefore did not receive the study drug. bDuring the 16-week treatment period. cOther reasons for treatment discontinuation were typically personal such as patient moving, loss of transportation to visits, and family illness. dEfficacy and safety analysis sets were identical and included all patients who received at least 1 dose of study treatment.

Figure 2.. Change From Baseline to Week 16 in WOMAC Pain, WOMAC Physical Function, and Patient Global Assessment of Osteoarthritis at the Patient Level

The black lines represent baseline values for each individual patient, sorted by severity. Individual colored lines represent the change from baseline at week 16 for each individual patient (colored lines extending below the black line indicate lower score and, thus, improvement at week 16). The pre (baseline) and post (week 16) boxplots show median (middle horizontal line in the box), and quartiles 1 and 3 (bottom and top lines of the box). Lines extend from the box to the smallest and largest observations no further than 1.5 times the interquartile range from quartile 1 and quartile 3, respectively, and any data beyond this range are plotted individually. WOMAC Pain subscale ranges from 0 = no pain to 10 = extreme pain. WOMAC Physical Function subscale ranges from 0 = no difficulty to 10 = extreme difficulty. PGA-OA scale ranges from 1 = very good to 5 = very poor. WOMAC indicates Western Ontario and McMasters Universities Osteoarthritis.