Development of an imaging mitigation strategy for patient enrolment in the tanezumab nerve growth factor inhibitor (NGF-ab) program with a focus on eligibility assessment

Roemer, Frank W.; Miller, Colin G.; West, Christine R.; Brown, Mark T.; Sherlock, Sarah P.; Kompel, Andrew J.; Diaz, Luis Eduardo Plumacher; Galante, N.; Crema, M.D.; Guermazi, Ali

doi:10.1016/j.semarthrit.2017.05.008

Cited by 12 publications

(14 citation statements)

References 36 publications

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“…In other studies, a similar increase in size of the calcified callus following fracture was also observed in animals that had received neonatal capsaicin, resulting in a 50% reduction in sensory nerve fibers innervating the skeleton and a 50% reduction in pain behaviors (guarding and flinching) following bone fracture [40]. These and other studies [32; 73], suggest that increased callus size is in part due to increased loading and use of the affected limb [64] and further research into the potential effects of NGF on bone formation and healing are clearly needed [33; 34; 78; 80; 95; 96].…”

Section: Discussionmentioning

confidence: 99%

Anti–nerve growth factor does not change physical activity in normal young or aging mice but does increase activity in mice with skeletal pain

Majuta

Mitchell

Kuskowski

et al. 2018

Pain

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Anti-nerve growth factor (anti-NGF) therapy has shown significant promise in attenuating several types of skeletal pain. However, whether anti-NGF therapy changes the level of physical activity in individuals with or without skeletal pain is largely unknown. Here, automated day/night activity boxes monitored the effects of anti-NGF treatment on physical activity in normal young (3 months old) and aging (18-23 months old) mice and mice with bone fracture pain. Although aging mice were clearly less active and showed loss of bone mass compared with young mice, anti-NGF treatment had no effect on any measure of day/night activity in either the young or aging mice. By contrast, in mice with femoral fracture pain, anti-NGF treatment produced a clear increase (10%-27%) in horizontal activity, vertical rearing, and velocity of travel compared with the Fracture + Vehicle group. These results suggest, just as in humans, mice titrate their level of physical activity to their level of skeletal pain. The level of skeletal pain may in part be determined by the level of free NGF that seems to rise after injury but not normal aging of the skeleton. In terms of bone healing, animals that received anti-NGF showed an increase in the size of calcified callus but no increase in the number of displaced fractures or time to cortical union. As physical activity is the best nondrug treatment for many patients with skeletal pain, anti-NGF may be useful in reducing pain and promoting activity in these patients.

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Section: Discussionmentioning

confidence: 99%

Anti–nerve growth factor does not change physical activity in normal young or aging mice but does increase activity in mice with skeletal pain

Majuta

Mitchell

Kuskowski

et al. 2018

Pain

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“…Key exclusion criteria were radiographic evidence of specified bone or joint conditions (RPOA, atrophic or hypotrophic OA, subchondral insufficiency fracture, spontaneous osteonecrosis of the knee, osteonecrosis or pathological fracture) or other conditions (excessive malalignment of the knee, severe chondrocalcinosis, other arthropathies [eg, rheumatoid arthritis], systemic metabolic bone disease, large cystic lesions, primary or metastatic tumour lesions, stress or traumatic fracture) identified by a group of centralised musculoskeletal radiologist readers 16. Also excluded were those with a history of osteonecrosis or osteoporotic fracture, significant trauma or surgery to a knee, hip or shoulder within the previous year.…”

Section: Methodsmentioning

confidence: 99%

Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period

et al. 2020

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ObjectiveTanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up.MethodsThis double-blind, randomised, phase III study enrolled adults in Europe and Japan with moderate-to-severe OA who had not responded to or could not tolerate standard-of-care analgesics. Patients were randomised to tanezumab 2.5 mg or 5 mg subcutaneously or matching placebo every 8 weeks (three doses). Co-primary end points were 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). Joint safety and neurological assessments continued throughout the 48-week study.ResultsFrom March 2016 to December 2017, 849 patients were randomised and evaluated (placebo n=282, tanezumab 2.5 mg n=283, tanezumab 5 mg n=284). At week 24, there was a statistically significant improvement from baseline for tanezumab 5 mg compared with placebo for WOMAC Pain (least squares mean difference±SE –0.62±0.18, p=0.0006), WOMAC Physical Function (–0.71±0.17, p<0.0001) and PGA-OA (–0.19±0.07, p=0.0051). For tanezumab 2.5 mg, there was a statistically significant improvement in WOMAC Pain and Physical Function, but not PGA-OA. Rapidly progressive osteoarthritis (RPOA) was observed in 1.4% (4/283) and 2.8% (8/284) of patients in the tanezumab 2.5 mg and tanezumab 5 mg groups, respectively and none receiving placebo. Total joint replacements (TJRs) were similarly distributed across all three treatment groups (6.7%–7.8%). Tanezumab-treated patients experienced more paraesthesia (5 mg) and hypoaesthesia (both doses) than placebo.ConclusionTanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumab 2.5 mg only achieved two co-primary end points. RPOA occurred more frequently with tanezumab 5 mg than tanezumab 2.5 mg. TJRs were similarly distributed across all three groups.Trial registration numberNCT02709486.

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“…Tanezumab clinical trials subsequent to the clinical hold, for example, have implemented a risk minimization plan excluding (1) chronic concomitant NSAID use, (2) higher exploratory tanezumab doses that have not demonstrated benefit over lower doses in the condition under study, and (3) subjects with evidence of, or risk factors for, RPOA. 44,94…”

Section: Ngf-abs Safety Profilementioning

confidence: 99%

Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety

Schmelz

Mantyh

Malfait

et al. 2019

Pain

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Key to a cultural transformation in pain care is a greater understanding-among members of the public and people with pain alike-of important aspects of chronic pain and its appropriate treatment. The National Pain Strategy recommends a national public awareness campaign involving public and private partners to address misperceptions and stigma about chronic pain. The learning objectives of the campaign would emphasize the impact and seriousness of chronic pain and its status as a disease that requires appropriate treatment. In addition, an educational campaign on the safer use of pain medications that is targeted to people with pain whose care includes these medications is recommended. Next Steps for Implementation Sustained efforts across HHS, working through operating divisions, staff divisions, and also with non-governmental partners, will be required in order to implement the public health, clinical, and research initiatives described in this Strategy. These efforts will help to prevent pain, improve patient care and outcomes, assure appropriate patient and provider education, and advance pain-related applied research. The Office of the Assistant Secretary for Health (OASH), in conjunction with HHS operating and staff divisions, will consider the recommendations included in the Strategy and develop an implementation and evaluation plan based on this process.

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Development of an imaging mitigation strategy for patient enrolment in the tanezumab nerve growth factor inhibitor (NGF-ab) program with a focus on eligibility assessment

Cited by 12 publications

References 36 publications

Anti–nerve growth factor does not change physical activity in normal young or aging mice but does increase activity in mice with skeletal pain

Anti–nerve growth factor does not change physical activity in normal young or aging mice but does increase activity in mice with skeletal pain

Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period

Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety

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