Model-based evaluation of cost-effectiveness of nerve growth factor inhibitors in knee osteoarthritis: impact of drug cost, toxicity, and means of administration

Abstract Background/Aims Osteoarthritis is a major cause of morbidity and disability. Much of this comes from joint pain, which is exacerbated by movement and exercise. Pharmacological analgesia therefore not only has the obvious benefit of alleviating pain, but in doing so, it also facilitates exercise (a pillar of conservative management). Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are currently the main analgesics used in this context. However, these agents can cause unwanted side effects and are contraindicated in some patients. We thus conducted a systematic review and meta-analysis using the Cochrane collaboration criteria to evaluate the efficacy of anti-nerve growth factor (anti-NGF) antibodies as potential alternative analgesics in osteoarthritis of the hip and/or knee. Whilst tanezumab has been studied extensively and monoclonal anti-NGF antibodies have been reviewed in other pain states, this is the first systematic review of three key anti-NGF antibodies: tanezumab, fulranumab and fasinumab in symptomatic hip and/or knee osteoarthritis. Methods An interdisciplinary work group conducted a literature search across seven electronic databases for the use of anti-NGF antibodies in osteoarthritis. All hip/knee osteoarthritis studies investigating anti-NGF antibodies regardless of dose regimen or phase of trial were included. Studies in which participants received NSAIDs or analgesics other than anti-NGF antibodies, or studies in which the only intervention was the administration of anti-NGF antibodies in combination with NSAIDs or other analgesics were excluded. The Jadad Scale score was used to assess the quality of each study. Results Thirteen studies involving 8,145 patients with a diagnosis of hip and/or knee osteoarthritis were analysed. Demographic information including duration of disease and Kellgren-Lawrence grades were also extracted. Anti-NGF antibodies showed significant improvements compared to placebo as rated on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scales for pain (SMD= -0.50, 95% CI -0.71 to -0.28, P < 0.00001; I2 = 88%), physical function (SMD= -0.82, 95% CI -1.09 to -0.55, P < 0.00001; I2 = 94%) and stiffness (SMD= -0.88, 95% CI -1.22 to -0.54, P < 0.00001; I2 = 95%). These agents were not associated with a significant increase in serious adverse events but were associated with a significant increase in discontinuation due to adverse events, abnormal peripheral sensations and peripheral neuropathy. Conclusion Anti-NGF antibodies appear very promising with regard to alleviating osteoarthritic hip/knee pain but more studies are needed to determine the optimal dosage and the overall risk-to benefit ratio, particularly with long-term use. Disclosure J. Rammanohar: None. J. Sutton: None. K. Seah: None. W.S. Khan: None. K. To: None.

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Faculty Opinions recommendation of Human osteocyte expression of Nerve Growth Factor: The effect of Pentosan Polysulphate Sodium (PPS) and implications for pain associated with knee osteoarthritis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736671650.793573707 ◽

2020 ◽

Author(s):

Susanne Grässel

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Knee Osteoarthritis ◽

Nerve Growth ◽

Pentosan Polysulphate

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Could nerve growth factor inhibitors have a place in the treatment of knee osteoarthritis?: Impact of joint destruction and means of administration ossn the value of Tanezumabs

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2015.02.727 ◽

2015 ◽

Vol 23 ◽

pp. A394 ◽

Cited By ~ 1

Author(s):

E. Losina ◽

G. Michl ◽

J. Collins ◽

D.J. Hunter ◽

J.M. Jordan ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Knee Osteoarthritis ◽

Joint Destruction ◽

Nerve Growth

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OP0293 Increased Nerve Growth Factor in the Synovium of People with Painful Knee Osteoarthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-eular.498 ◽

2013 ◽

Vol 72 (Suppl 3) ◽

pp. A153.1-A153

Author(s):

L. A. Stoppiello ◽

P. Mapp ◽

R. Hill ◽

D. Wilson ◽

B. Scammell ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Knee Osteoarthritis ◽

Nerve Growth ◽

Painful Knee

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A50 RN624 (ANTI-NERVE GROWTH FACTOR ANTIBODY) EFFECTIVELY REDUCES PAIN AND IMPROVES FUNCTION IN SUBJECTSWITH KNEE OSTEOARTHRITIS

Osteoarthritis and Cartilage ◽

10.1016/s1063-4584(07)60503-2 ◽

2006 ◽

Vol 14 ◽

pp. S41-S42

Author(s):

M. Mokhtarani ◽

C. Zhao ◽

M. Gray ◽

C. Chan ◽

F. Hefti

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Knee Osteoarthritis ◽

Nerve Growth

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Human osteocyte expression of Nerve Growth Factor: The effect of Pentosan Polysulphate Sodium (PPS) and implications for pain associated with knee osteoarthritis

PLoS ONE ◽

10.1371/journal.pone.0222602 ◽

2019 ◽

Vol 14 (9) ◽

pp. e0222602 ◽

Cited By ~ 3

Author(s):

Catherine J. M. Stapledon ◽

Helen Tsangari ◽

Lucian B. Solomon ◽

David G. Campbell ◽

Plinio Hurtado ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Knee Osteoarthritis ◽

Nerve Growth ◽

Pentosan Polysulphate

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Neuropathic pain in primary knee osteoarthritis patients: correlation with physical function, quality of life, disease severity, and serum beta nerve growth factor levels

Egyptian Rheumatology and Rehabilitation ◽

10.1186/s43166-021-00086-x ◽

2021 ◽

Vol 48 (1) ◽

Author(s):

Shereen R. Kamel ◽

Radwa S. Ibrahim ◽

Hend M. Moens ◽

Rania M. Mohammed

Keyword(s):

Quality Of Life ◽

Neuropathic Pain ◽

Nerve Growth Factor ◽

Growth Factor ◽

Knee Osteoarthritis ◽

Physical Function ◽

Disease Severity ◽

Nerve Growth ◽

Pain Symptoms

Abstract Background Neuropathic mechanisms are thought to play a role in knee osteoarthritis (KOA) pain. Neuropathic pain questionnaires can promote diagnosis of a neuropathic component. Thus, we aimed to assess the frequency of neuropathic pain in primary KOA patients (using clinical questionnaires) and to investigate its correlation with socio-demographic factors, physical function, quality of life, disease severity, and serum beta nerve growth factor (β-NGF) levels. Results Seventy primary KOA patients were included. Neuropathic pain was detected in 52.9% of patients based on Douleur Neuropathique en 4 Questions (DN4) questionnaire and in 38.6% of patients based on Leeds assessment neuropathic pain symptoms and signs questionnaire (LANSS). Serum β-NGF levels were significantly higher in KOA patients than controls (P<0.0001), and in KOA patients with neuropathic pain compared with patients with non-neuropathic pain. DN4 score was positively correlated with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and physical function, and it was also negatively correlated with Osteoarthritis knee hip quality of life questionnaire (OAKHQOL) pain scores (rs=0.459, P<0.001; rs= 0.258, P= 0.031; rs= 0.307, P= 0.010; rs = −0.337, P= 0.004, respectively), while LANSS scale was positively correlated with symptom duration, WOMAC stiffness, Lequesne pain, and Lequesne index (rs= 0.260, P= 0.020; rs= 0.343, P= 0.004; rs= 0.344, P= 0.004; rs= 0.322, P= 0.007) and negatively correlated with OAKHQOL physical, OAKHQOL mental health, OAKHQOL social support, and total OAKHQOL scores (rs= −0.258, P= 0.031;rs= −0.254, P= 0.034; rs= −0.283, P= 0.018; rs= −0.261, P= 0.029 respectively). Conclusions Neuropathic pain symptoms are frequent in primary KOA patients. KOA patients with neuropathic pain have worse quality of life, extreme disability, and higher serum β-NGF levels. Nerve growth factor inhibitors could have a potential role for not only relieving pain in KOA patients but also improving functional disability and quality of life in these patients.

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