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• W3152652554 abstract "Purpose: Tanezumab is a monoclonal antibody that inhibits nerve growth factor and has demonstrated efficacy in the management of osteoarthritis (OA). Due to the potential risk of rapidly progressive OA, recent phase 3 studies of subcutaneous tanezumab included a comprehensive prospective assessment of joint safety. This analysis summarizes data on patients who underwent total joint replacement (TJR) in recent phase 3 OA tanezumab studies. Methods: In study 1 (NCT02697773), patients received placebo, tanezumab 2.5 mg, or tanezumab 2.5 mg then 5 mg (tanezumab 2.5/5 mg) over 16 weeks. In study 2 (NCT02709486), patients received placebo, tanezumab 2.5 mg, or tanezumab 5 mg over 24 weeks. In study 3 (NCT02528188), patients received tanezumab 2.5 mg, tanezumab 5 mg, or nonsteroidal anti-inflammatory drug (NSAID) over 56 weeks. All 3 studies had a 24-week safety follow-up period. All tanezumab or matching placebo doses were administered subcutaneously every 8 weeks and NSAID was taken orally twice daily. TJR data were summarized and subgroup analyses were performed to investigate potential associations between TJR and baseline demographic or clinical characteristics and post-baseline outcomes. For all 3 studies, TJRs were adjudicated by a blinded, external Adjudication Committee to determine whether TJRs were associated with joint safety events, which included rapidly progressive OA type 1 (RPOA1) or type 2 (RPOA2), subchondral insufficiency fracture (SIF), primary osteonecrosis, or pathological fracture. For each patient, the most painful hip or knee joint with radiographic OA was selected as the index joint. Joint pain was assessed in all joints, but efficacy assessments were based upon the selected index joint. Patients may also have had OA in non-index joints. Results: Across the 3 studies (N=4541), a total of 248 patients had ≥1 TJR (26 patients had ≥2 TJRs), with an incidence of 4.5% in the placebo group, 5.5% in the tanezumab 2.5-mg group, 6.8% in the tanezumab 2.5/5-mg group, 7.8% in the tanezumab 5-mg group, and 2.6% in the NSAID group (Table 1).Table 1Summary of Total Joint Replacements — Patient LevelTanezumabPlacebo n=5142.5 mg n=15302.5/5 mg n=2195 mg n=1282NSAID n=996Patients with ≥1 TJR, n (%)23 (4.5)84 (5.5)15 (6.8)100 (7.8)26 (2.6)TJRs during study, no. (% pts with TJR)120 (87.0)77 (91.7)13 (86.7)87 (87.0)25 (96.1)≥23 (13.0)7 (8.3)2 (13.3)13 (13.0)1 (3.8)TJR of index joint, no. (% pts with TJR)20 (87.0)74 (88.1)14 (93.3)77 (77.0)22 (84.6)Adjudicated joint safety outcomes, no. (% pts with TJR)RPOA104 (4.8)1 (6.7)8 (8.0)2 (7.7)RPOA203 (3.6)010 (10.0)1 (3.8)Primary osteonecrosis0001 (1.0)0Pathological fracture00000Subchondral insufficiency fracture0003 (3.0)1 (3.8)Normal progression of OA21 (91.3)73 (86.9)14 (93.3)73 (73.0)22 (84.6)Insufficient information to determine rapid vs normal progression of OA02 (2.4)000Other joint outcomea2 (8.7)2 (2.4)05 (5.0)0Includes TJR or adjudicated event up to the end of the follow-up period or 26 weeks after the end of the treatment period, whichever is later. RPOA1 (rapidly progressive osteoarthritis type 1) is defined as a significant loss of joint space width ≥2 mm (predicated on optimal joint positioning) within∼1 year, without gross structural failure. RPOA2 (rapidly progressive osteoarthritis type 2) is defined as abnormal bone loss or destruction, including limited or total collapse of ≥1 subchondral surface, that is not normally present in conventional end-stage osteoarthritis. a Includes post-traumatic/post-procedure events and pre-existing conditions. no., number of events; NSAID, nonsteroidal anti-inflammatory drug; OA, osteoarthritis; pt, patient; TJR, total joint replacement. Open table in a new tab Includes TJR or adjudicated event up to the end of the follow-up period or 26 weeks after the end of the treatment period, whichever is later. RPOA1 (rapidly progressive osteoarthritis type 1) is defined as a significant loss of joint space width ≥2 mm (predicated on optimal joint positioning) within ∼1 year, without gross structural failure. RPOA2 (rapidly progressive osteoarthritis type 2) is defined as abnormal bone loss or destruction, including limited or total collapse of ≥1 subchondral surface, that is not normally present in conventional end-stage osteoarthritis. a Includes post-traumatic/post-procedure events and pre-existing conditions. no., number of events; NSAID, nonsteroidal anti-inflammatory drug; OA, osteoarthritis; pt, patient; TJR, total joint replacement. In all, 83% of patients with a TJR had surgery on their index joint. The proportion of patients with TJR of the index joint was similar in the placebo (87.0%), tanezumab 2.5 mg (88.1%), and NSAID (84.6%) treatment groups. In the tanezumab 5-mg and tanezumab 2.5/5-mg treatment groups, the proportion of patients with a TJR in their index joint was 77.0% and 93.3%, respectively. Most TJRs occurred in joints with Kellgren-Lawrence (KL) grade 3 or 4 at baseline (Table 2).Table 2Characteristics of Replaced Joints — Joint LevelTanezumabPlacebo n=5142.5 mg n=15302.5/5 mg n=2195 mg n=1282NSAID n=996TJRs, no.26911711427Joint(s) affected, no. (% pts with TJR)Knee13 (50.0)55 (60.4)10 (58.8)64 (56.1)15 (55.6)Hip13 (50.0)35 (38.5)7 (41.2)46 (40.4)11 (40.7)Shoulder01 (1.1)04 (3.5)1 (3.7)Index joint, no. (% pts with TJR)20 (76.9)74 (81.3)14 (82.4)77 (67.5)22 (81.5)Non-index joint, no. (% pts with TJR)6 (23.1)17 (18.7)3 (17.6)37 (32.5)5 (18.5)Baseline KL grade of replaced joint, no. (% pts with TJR)Not available01 (1.1)05 (4.4)2 (7.4)00002 (1.8)011 (3.8)003 (2.6)021 (3.8)7 (7.7)1 (5.9)14 (12.3)3 (11.1)316 (61.5)36 (39.6)8 (47.1)62 (54.4)16 (59.3)48 (30.8)47 (51.6)8 (47.1)28 (24.6)6 (22.2)KL, Kellgren-Lawrence; no., number of events; NSAID, nonsteroidal anti-inflammatory drug; pt, patient. Open table in a new tab KL, Kellgren-Lawrence; no., number of events; NSAID, nonsteroidal anti-inflammatory drug; pt, patient. There were 2 TJRs in patients in the tanezumab 5-mg group that occurred in joints that were KL grade 0 at baseline; 1 of these was adjudicated to be associated with RPOA2 and the other was a post-traumatic subchondral fracture following an accidental fall. The majority (73.3-81.0%) of patients across treatment groups had no prior history of TJR before participation in a study. Of the 275 TJRs reported across the treatment groups, 50.0-60.4% occurred in the knee, 38.5-50.0% in the hip, and 0-3.7% in the shoulder (Table 2). For placebo, tanezumab 2.5 mg or 2.5/5 mg, and NSAID treatment groups, the incidence of an adjudication outcome of normal progression of OA was similar (85-93%) and lower in the tanezumab 5-mg group (73%). The tanezumab 5-mg group had the highest percentage of patients with a TJR with an adjudicated outcome of RPOA1, RPOA2, or SIF (Table 1). Subgroup analyses did not reveal any associations between baseline demographic or clinical characteristics and TJR (Table 3).Table 3Subgroups Analyzed for Potential Association With Total Joint ReplacementSubgroupsDetailsAssociation with TJRDemographic factorsAge: <65 vs ≥65, <75 vs ≥75) Gender: Male vs female BMI: <25, 25 to <30, 30 to <35, ≥35No associationBaseline disease severityMaximum KL grade (2, 3, or 4) at baseline No. of joints with baseline KL grade ≥2 Prior history of TJR WOMAC∗ Pain subscale score at baseline (<7, ≥7) WOMAC Physical Function subscale score at baseline (<7, ≥7) Patient’s global assessment at baseline (Fair, Poor/Very Poor)No associationAdverse eventsSelected adverse events up to end of study: arthralgia, joint swelling, abnormal peripheral sensation, fracture, lower limb fracture, fall, peripheral edemaNo associationEfficacy response: WOMAC Pain and Physical functionChange from baseline in WOMAC Pain and Physical function scores at Week 16 and Week 56No associationConcomitant medications (non-NSAID)Use of intra-articular hyaluronic acid in year prior to study Use of intra-articular corticosteroid in year prior to study Concomitant use with NSAID Cardiovascular prophylactic aspirin Intra-articular corticosteroid Bisphosphonate AcetaminophenNo associationConcomitant NSAID useUse of NSAID prior to occurrence of TJRNo associationBaseline bone healthIncluding history of:Osteopenia OsteoporosisNo association Open table in a new tab ∗© 1996 Nicholas Bellamy. WOMAC® is a registered trademark of Nicholas Bellamy (CDN, EU, USA) BMI, body mass index; KL, Kellgren-Lawrence; NSAID, nonsteroidal anti-inflammatory drug; TJR, total joint replacement WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index Conclusions: Patients treated with tanezumab 5 mg had a greater incidence of TJR than patients receiving tanezumab 2.5 mg, placebo, or NSAID. The occurrence of TJR in the index joint in patients receiving tanezumab 2.5 mg was similar to those receiving placebo or NSAID. The majority of TJRs, across all treatment groups, was not associated with an adjudicated joint safety event but rather normal progression of OA and occurred in a joint with structural evidence of OA." @default.
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• W3152652554 date "2021-04-01" @default.
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• W3152652554 title "Total joint replacements in three phase 3 studies of tanezumab in patients with osteoarthritis" @default.
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