Tanezumab 5 mg significantly improves pain, physical function in hip, knee OA
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Among patients with hip or knee osteoarthritis, treatment with 5-mg doses of tanezumab statistically significantly improved pain, physical function and Patient’s Global Assessment of OA scores, while 2.5-mg doses achieved just two endpoints, according to data published in the Annals of the Rheumatic Diseases.
The researchers also found that rapidly progressive OA occurred more often among patients treated with 5 mg, compared with 2.5 mg, while total joint replacement was evenly distributed across both groups.
“Due to these joint safety concerns and histomorphological changes in the sympathetic nervous system observed in preclinical animal studies, the U.S. Food and Drug Administration placed partial clinical holds on studies of [nerve growth factor] NGF antibodies in 2010 and 2012, respectively,” Francis Berenbaum, MD, PhD, of Saint Antoine Hospital, in Paris, and colleagues wrote. “Investigation of these events provided evidence that led to the subsequent lifting of the tanezumab clinical holds, and an overall risk minimization strategy including comprehensive monitoring of joint and neurological safety was implemented in subsequent studies.”
They added, “The phase 3 OA program conducted after the clinical holds were removed (post-2015) used only lower doses of tanezumab administered subcutaneously 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.”
To analyze the effectiveness and safety of tanezumab (Pfizer, Eli Lilly) among patients with hip or knee OA, Berenbaum and colleagues conducted a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial at 104 hospitals, clinical research centers and general practices across Europe and Japan, from March 2016 to November 2018. Participants included 849 patients with moderate-to-severe OA who had not responded to, or were intolerant of, standard-of-care analgesics.
Investigators randomly assigned patients to receive either 2.5 or 5 mg of tanezumab subcutaneously, or matching placebo doses, every 8 weeks. In all, 282 participants received a placebo, 283 were treated with 2.5 mg and 284 received 5 mg. Coprimary end points included change from baseline to week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and Patient’s Global Assessment of OA (PGA-OA). Safety and neurological assessments continued through 48 weeks.
According to the researchers, there was a statistically significant improvement from baseline to week 24 among patients treated with 5-mg doses of tanezumab, compared with placebo, for WOMAC pain (least squares mean difference ± SE = –0.62 ± 0.18; P = .0006), WOMAC physical function (–0.71 ± 0.17; P < .0001) and PGA-OA (–0.19 ± 0.07; P = .0051).
Among participants treated with 2.5-mg doses, there was a statistically significant improvement in WOMAC pain and physical Function, but not PGA-OA. Additionally, rapidly progressive osteoarthritis was demonstrated in 1.4% of participants treated with 2.5 mg, 2.8% of those who received 5mg, and in zero patients in the placebo group. Total joint replacements were evenly distributed across all three treatment groups, with rates ranging from 6.7% to 7.8%.
Participants who received tanezumab demonstrated more paraesthesia — among the 5-mg group — and hypoaesthesia — both dosage groups — compared with those treated with a placebo.
“This study demonstrates subcutaneous tanezumab at a dose of 5mg every 8 weeks statistically significantly improves pain, physical function and PGA-OA at 24 weeks in patients with moderate-to-severe OA who have not responded to or could not tolerate standard-of-care analgesics,” Berenbaum and colleagues wrote. “Tanezumab 2.5mg improved pain and function in patients with moderate-to-severe OA, but did not reach statistical significance on the other co-primary end point, PGA-OA.”
“Adjudicated joint safety end points occurred only in tanezumab-treated patients, with RPOA in 1.4% and 2.8% of patients in the tanezumab 2.5mg and tanezumab 5mg groups, respectively, and in none receiving placebo,” they added. “The frequency of [total joint replacement] was similar across all three treatment groups.” – by Jason Laday
Disclosure: Berenbaum reports personal fees from 4P Pharma, Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GlaxoSmithKline, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov and TRB Chemedica. Please see the study for all other authors’ relevant financial disclosures.
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