The evolution of nerve growth factor inhibition in clinical medicine

Wise, Barton L; Seidel, Matthias; Lane, Nancy E.

doi:10.1038/s41584-020-00528-4

Cited by 97 publications

(81 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is also worrisome that despite recommendations from scientific societies, it seems that, to date, there are no specific measurements from health authorities to counterbalance such an increment in opioid utilization. Perhaps, and as mentioned above, novel analgesic therapies based on antibodies that inhibit the function of nerve growth factor that should be available soon could minimize the epidemic of opioid use [53,54].…”

Section: Yearmentioning

confidence: 99%

Disease Burden and Costs in Moderate-to-Severe Chronic Osteoarthritis Pain Refractory to Standard of Care: Ancillary Analysis of the OPIOIDS Real-World Study

Sicras‐Mainar¹,

Rejas‐Gutiérrez

Negrín³

et al. 2021

Rheumatol Ther

View full text Add to dashboard Cite

Introduction To determine the disease burden and costs in moderate-to-severe chronic osteoarthritis (OA) pain refractory to standard-of-care treatment in the Spanish National Health System (NHS). Methods Ancillary analysis of the OPIOIDS real-world, non-interventional, retrospective, 4-year longitudinal study including patients aged at least 18 years with moderate-to-severe chronic OA pain refractory to standard-of-care with sequential NSAIDs plus opioids. Burden assessment included measurement of analgesia, cognitive functioning, basic activities of daily living, severity and frequency of comorbidities, and all-cause mortality. Costs accounted for healthcare resource utilization and related costs (year 2018). Results Records of 13,317 patients were analyzed; 68.9 (14.7) years old, 71.3% (70.5–72.1%) women, 58.1% refractory to NSAID plus weak opioid and 41.9% to NSAID plus strong opioid, accounting for 10.7% (10.5–10.8%) of patients with chronic OA pain. Mean number of comorbidities was 2.9 (1.8) and its severity was 1.8 (1.7). Pain decreased by 0.9 points (12.2%) and cognitive declined by 2.3 points (9.1%, with 4.3% more patients with cognitive deficit) and dependency worsened by 0.4 points (0.5%, with 2.3% more patients with severe-to-total dependence) over a mean treatment period of 188.6 (185.4–191.8) days on NSAIDs followed by 400.6 (393.7–407.5) days on opioids. The adjusted mortality rate was higher in patients with OA taking NSAID plus strong opioids; hazard ratio 1.44 (1.26–1.65; p < 0.001). The 4-year healthcare cost was €7350/patient (€7193–7507 or €1838/year) and was higher in those taking strong versus weak opioids; €9886 (€9608–10,164, €2472/year) vs. €5519 (€5349–5689, €1380/year), p < 0.001. Analgesia cost (16.0% of total cost, 70.2% opioids) was higher with strong versus weak opioids, 19.6% vs. 11.3%, p < 0.001. Conclusions In routine clinical practice in Spain, patients with moderate-to-severe chronic OA pain refractory to standard analgesic treatment with NSAIDs plus opioids reported modest reductions in pain, while presenting a considerable burden of comorbidities, cognitive impairment, and dependency. Healthcare costs significantly increased for the NHS particularly with NSAIDs plus strong opioids. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-020-00271-y.

show abstract

Section: Yearmentioning

confidence: 99%

Disease Burden and Costs in Moderate-to-Severe Chronic Osteoarthritis Pain Refractory to Standard of Care: Ancillary Analysis of the OPIOIDS Real-World Study

Sicras‐Mainar¹,

Rejas‐Gutiérrez

Negrín³

et al. 2021

Rheumatol Ther

View full text Add to dashboard Cite

show abstract

“…Several mAbs that bind to NGF (ie tanezumab, fulranumab, and fasinumab) have been used in clinical studies for different chronic pain conditions, especially OA. (For a comprehensive review on this topic, see Wise et al 43 ) Specifically, phase I and phase II clinical trials have been conducted to test the efficacy of mAbs targeting NGF in pain attenuation in both knee and hip OA. 43–71 As described by Wise et al, 43 two primary endpoints have been used to study NGF inhibition in knee and hip OA in different studies: the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, which allows the meta-analyses of data; and function subscales, which are associated with the physician’s global assessment (PGA).…”

Section: Clinical Trials: Safety and Efficacy Of Anti-ngf Mabs In Chronic Pain Treatmentmentioning

confidence: 99%

“…(For a comprehensive review on this topic, see Wise et al 43 ) Specifically, phase I and phase II clinical trials have been conducted to test the efficacy of mAbs targeting NGF in pain attenuation in both knee and hip OA. 43–71 As described by Wise et al, 43 two primary endpoints have been used to study NGF inhibition in knee and hip OA in different studies: the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, which allows the meta-analyses of data; and function subscales, which are associated with the physician’s global assessment (PGA). Overall, all of these studies demonstrated the efficacy of anti-NGF antibodies in pain alleviation and an improvement of the main patient outcomes compared to placebo (used as a control) for hip and knee OA.…”

Section: Clinical Trials: Safety and Efficacy Of Anti-ngf Mabs In Chronic Pain Treatmentmentioning

confidence: 99%

“…Specifically, the clinical efficacy of tanezumab started from week 4 after initiation of treatment and persisted for another 8 weeks thereafter. As discussed by Wise et al, 43 whereas anti-NGF mAbs produced significant pain relief and functional improvement in patients with knee and/or hip OA, clinical trials and meta-analyses conducted with tanezumab on non-specific low back pain (LBP) gave mixed and confusing findings, but showed that LBP was less responsive to anti-NGF agents than OA, even when tanezumab was used at higher doses. In particular, the meta-analysis conducted by Sanga et al, on the efficacy of anti-NGF mAbs (tanezumab, fulranumab, and fasinumab) in the treatment of CLBP, showed a slight improvement of pain and functions and an increase in neurological adverse effects compared to placebo.…”

Section: Clinical Trials: Safety and Efficacy Of Anti-ngf Mabs In Chronic Pain Treatmentmentioning

confidence: 99%

“…From these studies, it emerged that RPOA was associated with higher doses of anti-NGF antibodies used alone or with NSAIDs, although the underlying molecular mechanism is currently unknown. As reported by Wise et al, 43 an adjudication was performed by independent committees of experts to understand the risks associated with the use of anti-NGF mAbs. 56 , 57 The clinical trial development programs subsequently resumed using lower doses of anti-NGF mAbs (2.5 and 5 mg for tanezumab) in patients with painful knee or hip OA.…”

Section: Adverse Effects Of Anti-ngf Mab Therapy For Oa: An Update On the Clinical Trialsmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Anti-Nerve Growth Factor Monoclonal Antibodies in the Control of Chronic Cancer and Non-Cancer Pain

Bimonte¹,

Cascella²,

Forte³

et al. 2021

JPR

View full text Add to dashboard Cite

Nerve growth factor (NGF) belongs to the neurotrophin family and plays a fundamental role in the endurance of sensory and sympathetic neurons during embryogenesis. NGF, by interacting with tropomyosin receptor kinase A receptor (TrkA), modulates the pain pathway through the enhancement of the neurotrophic and nociceptor functions. Moreover, it has been demonstrated that NGF is upregulated in patients with chronic pain syndromes, which are difficult to treat. Thus, new non-pharmacological approaches, based on the use of different species-specific monoclonal antibodies (mAbs) targeting the NGF pathway, have been tested for the treatment of chronic pain in preclinical and clinical studies. With regard to preclinical investigations, anti-NGF mAbs have been used for the management of osteoarthritis (OA) and chronic low back pain animal models, with encouraging results. Moreover, anti-NGF mAb therapy is effective in animal models of neuropathic cancer pain. As regards patients with OA, although phase II and phase III clinical trials with tanezumab led to pain reduction, the safety was not observed in all these patients. Here, we review the preclinical and clinical studies on anti-NGF mAb therapy in chronic syndromes, dissect the role of NGF in pain transduction, and highlight the use of anti-NGF mAbs in humans.

show abstract

Nanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms

Cheng

Xie

Zhao

et al. 2023

Brain-X

View full text Add to dashboard Cite

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Because of the complex pathogenesis of AD and the unique location of AD lesions, effective clinical treatment strategies for this disease remain elusive. However, the development of nanotechnology has allowed a new era of AD treatment to emerge. AD nanomedicines are products of interdisciplinary research that enable high precision and targeted delivery. Additionally, they can specifically regulate various pathogenic factors. This review focuses on nanomedicines based on the pathological mechanisms of AD that can target AD lesions. We also discuss the precise regulatory effects of nanomedicines (including the nanomaterials themselves) on pathogenic proteins, neuroinflammatory molecules, and other pathogenic factors. We summarize the clinical trials that have examined new AD drugs, highlighting the development of new nanomedicines and the progress in their clinical translation. Nanotechnology‐based AD treatment is a nascent field, and a complete cure is distant at present; therefore, we also elaborate on the shortcomings of current AD nanomedicines. Finally, we discuss the prospects to guide the future development of AD nanomedicines.

show abstract

The evolution of nerve growth factor inhibition in clinical medicine

Cited by 97 publications

References 95 publications

Disease Burden and Costs in Moderate-to-Severe Chronic Osteoarthritis Pain Refractory to Standard of Care: Ancillary Analysis of the OPIOIDS Real-World Study

Disease Burden and Costs in Moderate-to-Severe Chronic Osteoarthritis Pain Refractory to Standard of Care: Ancillary Analysis of the OPIOIDS Real-World Study

The Role of Anti-Nerve Growth Factor Monoclonal Antibodies in the Control of Chronic Cancer and Non-Cancer Pain

Nanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms

Contact Info

Product

Resources

About