Table 3

Summary of treatment-emergent adverse events (AEs) reported by the investigator

Patients, n (%)Treatment period
(first dose to week 24)
Up to end of study
(first dose to week 48)
Placebo
(n=282)
Tanezumab 2.5 mg
(n=283)
Tanezumab 5 mg
(n=284)
Placebo
(n=282)
Tanezumab 2.5 mg
(n=283)
Tanezumab 5 mg
(n=284)
Any AE155 (55.0%)150 (53.0%)162 (57.0%)178 (63.1%)184 (65.0%)198 (69.7%)
Serious AE*†3 (1.1%)8 (2.8%)9 (3.2%)11 (3.9%)24 (8.5%)27 (9.5%)
Treatment-related AE40 (14.2%)42 (14.8%)48 (16.9%)46 (16.3%)52 (18.4%)59 (20.8)
Discontinued study medication due to AE (and continued study)7 (2.5%)3 (1.1%)4 (1.4%)7 (2.5%)3 (1.1%)4 (1.4%)
Discontinued study due to AE2 (0.7%)5 (1.8%)1 (0.4%)2 (0.7%)6 (2.1%)4 (1.4%)
Most common AEs‡
 Arthralgia34 (12.1%)27 (9.5%)23 (8.1%)54 (19.1%)53 (18.7%)47 (16.5%)
 Nasopharyngitis25 (8.9%)31 (11.0%)22 (7.7%)33 (11.7%)39 (13.8%)30 (10.6%)
 Back pain15 (5.3%)16 (5.7%)17 (6.0%)23 (8.2%)27 (9.5%)25 (8.8%)
 Headache18 (6.4%)15 (5.3%)14 (4.9%)21 (7.4%)20 (7.1%)16 (5.6%)
 Osteoarthritis5 (1.8%)9 (3.2%)13 (4.6%)9 (3.2%)17 (6.0%)26 (9.2%)
 Paraesthesia5 (1.8%)5 (1.8%)12 (4.2%)6 (2.1%)6 (2.1%)12 (4.2%)
 Influenza5 (1.8%)5 (1.8%)9 (3.2%)5 (1.8%)9 (3.2%)11 (3.9%)
 Fall8 (2.8%)12 (4.2%)7 (2.5%)13 (4.6%)19 (6.7%)9 (3.2%)
 Pain in extremity7 (2.5%)9 (3.2%)5 (1.8%)11 (3.9%)16 (5.7%)9 (3.2%)
 Musculoskeletal pain7 (2.5%)6 (2.1%)7 (2.5%)14 (5.0%)13 (4.6%)11 (3.9%)
 Joint swelling3 (1.1%)6 (2.1%)8 (2.8%)4 (1.4%)7 (2.5%)10 (3.5%)
 Neck pain4 (1.4%)3 (1.1%)2 (0.7%)10 (3.5%)5 (1.8%)4 (1.4%)
 Urinary tract infection4 (1.4%)6 (2.1%)2 (0.7%)6 (2.1%)9 (3.2%)4 (1.4%)
 Rapidly progressive osteoarthritis01 (0.4%)2 (0.7%)04 (1.4%)11 (3.9%)
AE of abnormal peripheral sensation§
 Paraesthesia5 (1.8%)5 (1.8%)12 (4.2%)6 (2.1%)6 (2.1%)12 (4.2%)
 Hypoaesthesia¶2 (0.7%)4 (1.4%)6 (2.1%)2 (0.7%)7 (2.5%)7 (2.5%)
 Decreased vibratory sense3 (1.1%)01 (0.4%)3 (1.1%)1 (0.4%)2 (0.7%)
  • AEs based on the usual definition for clinical trials. A blinded adjudication committee reviewed all possible or probable joint safety events resulting in differences in reported joint AEs (table 3) and adjudicated joint events (table 4).

  • *AEs were considered serious based on established definition.17 During the double-blind treatment period, three patients in the placebo group had serious AEs, including one with cataract, one with osteoarthritis and one with lymphatic fistula. Eight patients in the tanezumab 2.5 mg group had serious AEs, including three with four nerve injuries or bone fractures, one with acute myocardial infarction and coronary artery stenosis and one each with ocular vascular disorder, cerebrovascular accident, osteoarthritis and rotator cuff syndrome. Nine patients in the tanezumab 5 mg group had serious AEs, including two with three hepatobiliary disorders, two with osteoarthritis and one each with arrhythmia, cardiorespiratory arrest, pancreatitis, nasopharyngitis, pneumonia and arthralgia.

  • †There were three deaths during the study. Two deaths occurred during the double-blind treatment period in patients in the tanezumab 5 mg treatment group: neither were considered by the investigator to be related to study medication (one patient, aged 81 years, died on study day 90, with the cause of death reported as severe cold with probable influenza virus infection. The other patient, aged 77 years, was found dead at home on study day 114; the event was reported as cardiorespiratory arrest). The third patient aged 60 years, in the tanezumab 2.5 mg treatment group, died of cerebrovascular accident. This patient was lost to follow-up and the death was not confirmed by the family or the doctor (it was stated on a returned letter that had been sent to the patient by the study site as part of attempts by the investigator to make contact with the patient).

  • ‡Reported in ≥3% of patients in any treatment group up to end of study.

  • §Reported in ≥1% of patients in any treatment group during the treatment period.

  • ¶One patient with mild hypoaesthesia of the left index finger discontinued treatment in the tanezumab 5 mg group after two doses of study drug, completed the safety follow-up period and the adverse event was ongoing at study end. The patient was evaluated by a local neurologist and cervical spine MRI showed disc protrusion at C5-C6 and C6-C7 and a nerve conduction study showed a mild left-sided carpal tunnel syndrome. The external expert neurologist considered the patient to have had carpal tunnel syndrome.