Abstract| Volume 28, SUPPLEMENT 1, S29, April 2020

Postoperative outcome of patients who underwent total joint replacement during the tanezumab phase 3 osteoarthritis development program: a 24-week observational study

      Purpose: Tanezumab, a monoclonal antibody against nerve growth factor, is in development for the treatment of osteoarthritis (OA). The aim of this study was to evaluate the postoperative outcome of patients who had undergone a total joint replacement (TJR) while participating in one of three parent tanezumab phase 3 OA studies.
      Methods: This phase 3 observational study (NCT02674386) followed consenting patients from three phase 3 randomized controlled trials, who underwent TJR (knee, hip, or shoulder) at any time (during the parent study treatment period or safety follow up period), for 24 weeks after surgery. Endpoints included: Surgeon’s Assessment of Procedural Difficulty (uneventful, minor complications, major complications) at the time of TJR; post-surgical complications (clinically significant events attributable to the TJR, derived from adverse events) up to Week 24; additional or corrective procedures (procedures or investigations related to the TJR) up to Week 24; and patient’s overall satisfaction with the result of surgery (based on the question ‘How satisfied are you with the results of your surgery?’; somewhat satisfied, very satisfied, somewhat dissatisfied, or very dissatisfied) at Week 24. Patients were contacted by telephone (to collect information on adverse events and planned further procedures) and at prespecified time points they completed questionnaires. An external Adjudication Committee utilized clinical study data and magnetic resonance images/radiographs to determine in a blinded and independent fashion the presence of: primary osteonecrosis, rapidly progressive OA (RPOA) type 1 (rapid loss of joint space width ≥ 2mm within a year) or type 2 (abnormal bone loss/joint destruction), normal progression of OA (NPOA), subchondral insufficiency fracture, pathological fracture, other joint outcome, or not enough information to differentiate RPOA vs NPOA or specify a diagnosis.
      Results: Of 258 patients with a TJR, 154 (59.7%) consented and were enrolled in the current study; data from 150 patients with 169 TJRs (99 knees [58.6%], 69 hips [40.8%], and 1 shoulder [0.6%]) were eligible for evaluation. At baseline in the parent studies 91.1% [154/169] of the joints were Kellgren-Lawrence radiographic severity grade 3 or 4. In the parent studies the patients received placebo (n=20), tanezumab 2.5 mg (n=52), tanezumab 5 mg (n=53), tanezumab 2.5 mg titrated to 5 mg (tanezumab 2.5/5 mg, n=8), or a nonsteroidal anti-inflammatory drug (NSAID; n=17). The TJR was performed 299 days (mean) from randomization in the parent studies. Based on the joint with the worst adjudicated outcome, the 150 patients were adjudicated to have osteonecrosis (n=1), RPOA type 1 (n=3), RPOA type 2 (n=8), NPOA (n=130), other joint outcome (n=6), or not enough information to determine RPOA vs NPOA (n=2). A total of 95.1% (116/122) of patients had Surgeon’s Assessment of Procedural Difficulty ratings of uneventful and none had major complications. Of 6 patients with procedural difficulty ratings of minor complications, 4 had hip TJRs which were adjudicated as NPOA (tanezumab 2.5 mg n=1, tanezumab 5 mg n=1) or RPOA type 2 (tanezumab 5 mg n=2) and 2 had knee TJRs (both adjudicated as NPOA, tanezumab 5 mg). The minor complications included difficulty removing the head of the joint, abnormal bone appearance, osteosclerosis, capsule stenosis, and accumulation of synovial fluid. Through the 24-week study, 4.0% (6/150) of patients had post-surgical complications (5 hip TJRs and 1 knee TJR, all adjudicated as NPOA: tanezumab 2.5 mg n=2, tanezumab 5 mg n=4). These included: hematoma/periprosthetic fracture/hip infection; incision site infection; luxation of prosthesis joint; anemia; and periprosthetic infection/hip dislocation. A total of 6.7% (10/150) of patients required additional or corrective procedure(s) (6 hip TJRs and 4 knee TJRs, adjudicated as NPOA [n=9] or RPOA type 2 [n=1]: tanezumab 2.5 mg n=3, tanezumab 5 mg n=6, NSAID n=1), including: fracture treatment/hematoma evacuation/surgery; joint debridement, manipulation or fluid drainage; device repositioning; tendon repair; and imaging. At Week 24, 6.1% (8/131) of patients were somewhat dissatisfied or very dissatisfied with the result of the surgery (2 hip TJRs and 6 knee TJRs, adjudicated as NPOA [n=7] or other joint outcome [n=1]: placebo n=1, tanezumab 2.5 mg n=4, tanezumab 5 mg n=2, NSAID n=1).
      Conclusions: Procedural difficulty of minor complications during surgery, post-surgical complications, and additional or corrective procedures were infrequent, but occurred primarily in patients treated with tanezumab in the parent studies, and more frequently with tanezumab 5 mg than tanezumab 2.5 mg. Most of these cases were adjudicated as NPOA. The TJR outcomes in the patients with RPOA were similar to NPOA. Few patients were dissatisfied with their TJR, most of them were previously treated with tanezumab.