Tanezumab effective for hip, knee osteoarthritis
Use of the nerve growth factor (NGF) inhibitor tanezumab led to significant improvements in pain and physical function in patients with moderate-to-severe osteoarthritis (OA) of the hip and knee who have intolerance or insufficient response to standard analgesics*, a phase III study has shown.
Patients with hip/knee OA have a high mortality risk due to increased risk of cardiovascular events. [https://www.oarsi.org/sites/default/files/docs/2016/oarsi_white_paper_oa_serious_disease_121416_1.pdf, accessed May 16, 2020] Despite current strategies combining non-pharmacologic modalities and analgesics, concerns about adverse events (AEs) and limited efficacy warrant an alternative pharmacologic approach. [Ann Rheum Dis 2018;77:797-807] “This study demonstrates the efficacy of SC tanezumab in difficult-to-treat patients with OA,” said the researchers.
A total of 849 participants (69 percent female) were randomized 1:1:1 to receive SC tanezumab 2.5 or 5 mg, or matching placebo, every 8 weeks for 24 weeks. A 24-week post-treatment follow-up period ensued to evaluate safety. [Ann Rheum Dis 2020;doi:10.1136/annrheumdis-2019-216296]
Week 24 saw statistically significant improvements with both tanezumab doses vs placebo in terms of WOMAC** Pain (least squares mean difference [LSMD], –0.46; p=0.0088 [2.5 mg] and –0.62; p=0.0006 [5 mg]) and Physical Function (LSMD, –0.59; p=0.0008 and –0.71; p<0.0001, respectively).
These findings mirrored those of other studies evaluating IV-administered tanezumab at similar doses and in a similar patient setting. [J Pain 2012;13:790-798; Arthritis Rheum 2013;65:1795-1803]
Despite the less severe baseline WOMAC Pain scores in the current study vs the above-noted studies, baseline joint radiographic findings were more severe in the former than the latter, noted the researchers. “[While] the association between pain and radiographic findings has not always been consistent … a relationship has been reported for knee OA,” they said.
“[Moreover,] the proportion of patients with moderate or substantial clinically important improvement in WOMAC Pain with tanezumab … was statistically significant in the current study, although smaller than [those] observed in the IV tanezumab … studies,” they added.
This comparison between the current study and those on IV-administered tanezumab highlights the potential of SC administration to obtain effects similar to those achieved with an IV-administered dose, the researchers pointed out.
More than half of participants across all arms reported AEs during the treatment period (53–57 percent). Back pain and OA were the more frequent AEs with both tanezumab doses. Serious AE rates were low across all arms (1–3 percent) and none was treatment-related. These findings suggest that tanezumab was generally well tolerated throughout the treatment and safety periods, noted the researchers.
The US Food and Drug Administration has previously placed partial clinical holds on studies of NGF antibodies in view of safety concerns and histomorphological changes in the sympathetic nervous system seen in preclinical trials. [Toxicol Sci 2017;158:319-333] Nonetheless, further probing into these issues led to the consequent lifting of these holds, noted the researchers.
“[After 2015, studies only used] lower doses of [SC-administered] tanezumab in difficult-to-treat patients, incorporated extensive risk mitigation and surveillance, excluded patients with evidence of or risk factors for RPOA*** or who were unsuitable for joint replacement, and restricted chronic concomitant use of NSAIDs# while in the study,” said the researchers.
The current findings thus underscore the potential role of a lower, SC-administered tanezumab dose in OA management, noted the researchers, who called for longer-term trials with active comparators to ascertain the risk-benefit of tanezumab in this setting.