FRI0392 ADVERSE EVENTS IN PATIENTS WITH OSTEOARTHRITIS TREATED WITH SUBCUTANEOUS TANEZUMAB: A POOLED ANALYSIS OF THE OVERALL POPULATION AND SELECTED SUBGROUPS FROM 3 RANDOMISED PLACEBO-CONTROLLED TRIALS
Authors: F. Berenbaum, A. Kivitz, T. Schnitzer, M. Brown, S. Donevan, A. Hickman, L. Viktrup, C. West, T. Yamabe
Journal: Annals of the Rheumatic Diseases (2020)

Background: Tanezumab, a monoclonal antibody against nerve growth factor (NGF), is in development for the treatment of osteoarthritis (OA). Objectives: To assess the effects of gender, age and body mass index (BMI) on the incidence of adverse events (AEs) in patients (pts) treated with subcutaneous (SC) tanezumab in pooled data from three phase 3 OA studies. Anti-NGF therapy has been associated with joint safety events 1 . Here we focus on treatment emergent AEs, including abnormalities of peripheral sensation (APS). Methods: All three randomised, double-blind, placebo-controlled studies enrolled pts with radiographically-confirmed OA of the hip or knee, who had inadequate response or could not tolerate standard of care analgesics. In the 16-week (wk) Study 1 ( NCT01089725 ), pts received placebo, tanezumab 2.5 mg, 5 mg or 10 mg at baseline and wk 8 2 . Due to a clinical hold on NGF antibodies, &lt;10% of pts received the 2 nd dose at wk 8. Pts in the 16-wk Study 2 ( NCT02697773 ), received placebo or tanezumab 2.5 mg at baseline and wk 8 or tanezumab 2.5mg at baseline and 5mg at wk 8 1 . Pts in the 24-wk Study 3 ( NCT02709486 ), received placebo, tanezumab 2.5 mg or 5 mg at baseline, wks 8 and 16. All treatments were given SC. AE data from the treatment period of each study were pooled for placebo, tanezumab 2.5 mg and 5 mg groups and examined by subgroups of gender, age and BMI. Data from the 10 mg group of Study 1 were not included due to the low sample size. Results: The incidence of any AE was numerically higher in females across treatment groups and in pts with a BMI ≥30 kg/m 2 in the tanezumab 5mg, but not 2.5 mg group, vs the overall population (Table 1). SAEs were infrequent but numerically higher across all tanezumab 5 mg subgroups vs placebo (Table 2). Paraesthesia and hypoaesthesia were the most common AEs of APS and were increased in all tanezumab groups in the overall population vs placebo. In any of the subgroups, the incidence of paraesthesia or hypoaesthesia was ≤7.8% and ≤3.9%, respectively. The difference within a patient subgroup for paraesthesia or hypoaesthesia was typically comparable with that of the overall population across treatments. Table 1. Incidence of AEs during the treatment period % of pts with an AE in each subgroup Placebo n=586 Tanezumab 2.5 mg n=602 Tanezumab 2.5 mg/5 mg n=219 Tanezumab 5 mg n=347 Overall population 51.7 52.3 47.0 54.8 Gender Male 51.1 49.7 41.3 46.6 Female 52.0 53.6 50.4 59.0 Age (years) &lt;65 55.0 54.0 44.0 54.5 ≥65 47.2 50.0 52.6 54.9 BMI (kg/m 2 ) &lt;25 58.1 46.6 51.9 45.5 25–&lt;30 51.4 55.9 43.7 50.0 30–&lt;35 49.2 51.5 43.2 58.9 ≥35 52.7 52.3 55.3 60.9 BMI, body mass index; kg/m2, kilogram per square metre Table 2. Incidence of SAEs during the treatment period % of pts with a SAE in each subgroup Placebo n=586 Tanezumab 2.5 mg n=602 Tanezumab 2.5 mg/5 mg n=219 Tanezumab 5 mg n=347 Overall population 1.5 2.2 1.4 2.6 Gender Male 1.6 3.0 1.3 2.5 Female 1.5 1.7 1.4 2.6 Age (years) &lt;65 1.2 2.6 1.4 1.9 ≥65 2.0 1.6 1.3 3.1 BMI (kg/m 2 ) &lt;25 1.6 1.1 0 2.3 25–&lt;30 1.6 2.7 0 2.7 30–&lt;35 1.6 2.0 1.4 3.1 ≥35 1.3 2.3 4.3 1.6 BMI, body mass index; kg/m2, kilogram per square metre Conclusion: This pooled analysis showed that the safety profile of tanezumab in the subgroups studied is broadly similar to that of the overall study population. References: [1]Schnitzer, T. J. et al. JAMA (2019) [2]Birbara, C. et al. J Pain Res (2018) Disclosure of Interests: Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Thomas Schnitzer Consultant of: Pfizer, Lilly, AstraZeneca, GSK, Mark Brown Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Sean Donevan Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., Anne Hickman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christine West Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Takaharu Yamabe Shareholder of: Pfizer, Employee of: Pfizer