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Original Investigation
July 2, 2019

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

Author Affiliations
  • 1Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 2Michigan Orthopaedic & Spine Surgeons, Rochester Hills
  • 3St Joseph Heritage Healthcare, Fullerton, California
  • 4Chicago Clinical Research Institute, Chicago, Illinois
  • 5Pfizer Inc, Morrisville, North Carolina
  • 6Eli Lilly and Company, Indianapolis, Indiana
  • 7Pfizer Inc, Groton, Connecticut
JAMA. 2019;322(1):37-48. doi:10.1001/jama.2019.8044
Key Points

Question  Among patients with moderate to severe osteoarthritis of the knee or hip and inadequate treatment response to standard analgesics, what is the effect of subcutaneous tanezumab on joint pain, physical function, and patient global assessment of osteoarthritis?

Findings  In this randomized clinical trial that enrolled 698 patients, subcutaneous tanezumab administered with fixed doses at 8-week intervals or with a forced titration at week 8, compared with placebo, resulted in statistically significant improvements in joint pain, physical function, and patient global assessment of osteoarthritis over 16 weeks, although the improvements were modest and tanezumab-treated patients had more joint safety events and total joint replacements.

Meaning  Further research is needed to determine the clinical importance of these efficacy and adverse event findings with regard to use of tanezumab for treatment of osteoarthritis.

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

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