Fasinumab in the treatment of hip and knee osteoarthritic pain: efficacy and safety in a 36-week randomized, double-blind placebo-controlled clinical trial

Maloney, Jennifer; Kivitz, A.; Schnitzer, Thomas J.; Dakin, Paula; Martino, S; Gao, Haitao; Stehman‐Breen, Catherine; Geba, Gregory P.

doi:10.1016/j.joca.2017.02.102

Cited by 3 publications

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“…Several phase III trials were finished in 2016, but no results have come out yet. Fasinumab Randomized, double-blind, placebo-controlled trial showed improvement of pain and function, while generally being well tolerated [ 40 ]. Several phase III trials are currently recruiting patients (NCT02683239, NCT03304379, and NCT03161093), as well as a trial to self-administer fasinumab (NCT03491904).…”

Section: Current and Recent Targets In Chondroprotectionmentioning

confidence: 99%

“…No further studies registered to date.PainNerve growth factor (NGF)TanezumabAfter a successful phase I trial [37] and an earlier successful proof-of-concept study [38], now many studies in progress awaiting results.FalranumabPhase II double-blind placebo-controlled trial showed positive results on pain but risk of rapid OA progression [39]. Several phase III trials were finished in 2016, but no results have come out yet.FasinumabRandomized, double-blind, placebo-controlled trial showed improvement of pain and function, while generally being well tolerated [40]. Several phase III trials are currently recruiting patients (NCT02683239, NCT03304379, and NCT03161093), as well as a trial to self-administer fasinumab (NCT03491904).Trans-capsaicinCNTX-4975Phase II revealed that a single injection improved pain with walking, knee stiffness, and physical function in OA patients with knee pain [41].…”

Section: Current and Recent Targets In Chondroprotectionmentioning

confidence: 99%

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Chondroprotective Factors in Osteoarthritis: a Joint Affair

Mimpen

Snelling

2019

Curr Rheumatol Rep

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Purpose of the Review Osteoarthritis is widely regarded as a spectrum of conditions that affect all joint tissues, typified by a common entity: cartilage loss. Here, we review recent progress and challenges in chondroprotection and discuss new strategies to prevent cartilage loss in osteoarthritis. Recent Findings Advances in clinical, molecular, and cellular characterization are enabling improved stratification of osteoarthritis subtypes. Integration of next-generation sequencing and "omics" approaches with clinically relevant readouts shows promise in delineating both subtypes of disease and meaningful trial end points. Novel delivery strategies are enabling jointspecific delivery. Summary Chondroprotection requires a whole joint approach, stratification of patient groups, and use of patient-relevant end points. Drug development should continue to explore new targets, while using modern technologies and recent knowledge to revisit unsuccessful therapeutics from the past. The overarching goal for chondroprotection is to provide the right treatment(s) for the right patient at the right time.

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Section: Current and Recent Targets In Chondroprotectionmentioning

confidence: 99%

Section: Current and Recent Targets In Chondroprotectionmentioning

confidence: 99%

Chondroprotective Factors in Osteoarthritis: a Joint Affair

Mimpen

Snelling

2019

Curr Rheumatol Rep

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“…In contrast to anti-NGF inhibitors, they target the mechanistic pathophysiology of osteoarthritis by regulating catabolic and anabolic processes in the cartilage and bone or inflammatory responses in the synovium, but do not address the modulation of acute and chronic pain by effecting nociceptor sensitization. Anti-NGF antibodies have demonstrated promising results in alleviating pain associated with OA ( Miller et al, 2014 ; Schnitzer and Marks, 2015 ; Kan et al, 2016 ; Chen et al, 2017 ) but at the same time clinical trials have revealed serious adverse effects including rapidly progressive OA (RPOA) and osteonecrosis ( Hochberg, 2015 ; Maloney et al, 2016 ; Lane and Corr, 2017 ). Therefore, United States and European health authorities have not yet approved this treatment option ( EMA, 2021 ; FDA, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Anti-NGF treatment worsens subchondral bone and cartilage measures while improving symptoms in floor-housed rabbits with osteoarthritis

2023

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Objective: Osteoarthritis (OA) is a common joint disorder often affecting the knee. It is characterized by alterations of various joint tissues including subchondral bone and by chronic pain. Anti-nerve growth factor (NGF) antibodies have demonstrated improvement in pain associated with OA in phase 3 clinical trials but have not been approved due to an increased risk of developing rapidly progressive OA. The aim of this study was to investigate effects of systemic anti-NGF-treatment on structure and symptoms in rabbits with surgically induced joint instability.Methods: This was elicited by anterior cruciate ligament transection and partial resection of the medial meniscus in right knee of 63 female rabbits, housed altogether in a 56 m2 floor husbandry. Rabbits received either 0.1, 1 or 3 mg/kg anti-NGF antibody intra-venously at weeks 1, 5 and 14 after surgery or vehicle. During in-life phase, static incapacitance tests were performed and joint diameter was measured. Following necropsy, gross morphological scoring and micro-computed tomography analysis of subchondral bone and cartilage were performed.Results: After surgery, rabbits unloaded operated joints, which was improved with 0.3 and 3 mg/kg anti-NGF compared to vehicle injection during the first half of the study. The diameter of operated knee joints increased over contralateral measures. This increase was bigger in anti-NGF treated rabbits beginning 2 weeks after the first IV injection and became dose-dependent and more pronounced with time. In the 3 mg/kg anti-NGF group, the bone volume fraction and trabecular thickness increased in the medio-femoral region of operated joints compared to contralateral and to vehicle-treated animals, while cartilage volume and to a lesser extent thickness decreased. Enlarged bony areas were found in right medio-femoral cartilage surfaces of animals receiving 1 and 3 mg/kg anti-NGF. Alterations of all structural parameters were particularly distinct in a subgroup of three rabbits, which also exhibited more prominent symptomatic improvement.Conclusion: This study showed that anti-NGF administration exerted negative impact on structure in destabilized joints of rabbits, while pain-induced unloading of joints was improved. Our findings open up the possibility to better understand the effects of systemic anti-NGF, particularly on subchondral bone, and thus the occurrence of rapidly progressive OA in patients.

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