The Efficacy, Tolerability, and Joint Safety of Fasinumab in Osteoarthritis Pain: A Phase IIb/III Double‐Blind, Placebo‐Controlled, Randomized Clinical Trial

Abstract

ObjectiveTo prospectively assess the efficacy, general safety, and joint safety of fasinumab, an anti–nerve growth factor monoclonal antibody, in osteoarthritis (OA) hip and/or knee pain.MethodsPatients with moderate‐to‐severe OA pain (knee or hip) and history of inadequate response or intolerance to analgesics were randomized to receive fasinumab (at 1 mg, 3 mg, 6 mg, or 9 mg) or placebo every 4 weeks over 16 weeks and were followed up to week 36. Efficacy end points were the change from baseline to week 16 in the pain and physical function subscale scores of the Western Ontario and McMaster Universities OA Index (WOMAC), and patient global assessment (PGA) of OA. Joints were monitored at scheduled assessments (by plain film radiography and magnetic resonance imaging) during treatment and follow‐up, and if prompted, at the time of active joint symptoms.ResultsOf the 421 patients randomized, 342 completed the 36‐week study. All doses of fasinumab yielded statistically significant and clinically important reductions in pain compared to placebo (least squares mean difference in WOMAC pain subscale scores at week 16 ranging −0.78 to −1.40), without any clear dose dependence. Physical function and PGA scores improved in parallel. Treatment‐emergent adverse event rates were 17% with fasinumab and 10% with placebo, and 4% and 1% of patients, respectively, discontinued treatment. Arthropathies (25 in total, 7% of fasinumab‐treated patients and 1% of placebo‐treated patients) occurred in a dose‐dependent manner, with 2 occurring in patients receiving the lowest dose of fasinumab and 10 in patients receiving the highest dose. Most of the arthropathies (16 of 25) were discovered with scheduled radiographs and not based on symptoms. Destructive arthropathy (in 1 of 337 treated patients) occurred in 1 patient who was receiving 6 mg fasimumab.ConclusionFasinumab provided improvements in OA pain and function, even in those benefitting little from previous analgesics. The observed benefit‐to‐risk relationship favors further clinical development to explore the lowest doses of fasinumab in patients with knee or hip OA.

Understanding the Molecular Mechanisms Underlying the Pathogenesis of Arthritis Pain Using Animal Models

“…NGF induces sensitization of peripheral nociceptive terminals as well as the development of the nervous system, and plays a key role in acute and chronic pain [33]. Biologic agents that specifically block NGF revealed dramatic pain relief among OA patients, and despite their unique side effect profile, such as alterations in peripheral sensation and development of arthropathies, they are in active clinical development [34,35] [36]. Surgically induced OA models reflect posttraumatic human OA and include destabilization of the medial meniscus (DMM), anterior cruciate ligament transection (ACLT), and medial meniscal transection (MNX) models.…”

New Molecular Targets in the Therapy of Arthrosis Patients

“…As a result to a research into various clinical trial registers (Arthritis Clinical Trials, Clinical Research and Drug Information) and on specialized e-platforms, 5 randomized, multicentric double-blind clinical studies (20)(21)(22)(23)(24) have been identified, which monitored the efficiency of various biological molecules in the treatment of arthrosis (etanercept, adalimumab, litikizumab, fasinumab and tanezumab).…”

Інформаційне Забезпечення Доказового Ведення Пацієнтів З Ураженнями Кістково-М’язової Системи В Первинній Ланці Охорони Здоров’я

“…Nowadays, a category search is unavailable in the TRIP. Evidence may be found either by search terms that match the PICO components (Patient, Intervention, Comparison, [19]; 2) a double blind phase IIb/III RCT of using fasinumab for osteoarthritic pain, reported by Dakin P. et al [20]; 3) «a mixed methods study protocol» as to effectiveness, cost-utility, and benefit of a multicomponent therapy to improve the quality of life of patients with FM in primary care, by Caballol Angelats R. et al [21]; 4) a mixed method evaluation of a primary care-based opioid's acceptability for chronic non-cancer pain, conducted by Kesten J. et al [22]. We are reporting the obtained results, taking into account their novelty.…”

“…Dakin P. et al concluded that fasinumab alleviated OA pain and improved function even when analgetics were ineffective. They suggested an expediency of further studying «the lowest doses of fasinumab in patients with knee or hip ОА» [20].…”