POS1126 CLINICAL EFFICACY AND SAFETY OF MONOCLONAL ANTIBODY AGAINST NERVE GROWTH FACTOR AND FIBROBLAST GROWTH FACTOR-18 THERAPY OF OSTEOARTHRITIS

Abstract

BackgroundOsteoarthritis (OA) is the most common chronic progressive musculoskeletal system disease affecting more than 500 million people globally, which represents the formidable public health challenge. Currently osteoarthritis treatment includes acetaminophen, NSAIDs and/or opioids, intra-articular corticosteroid injections. Some guidelines also recommended chondroitin and glucosamine sulfate, suggested that they may be effective and reduce functional impairment. However, despite of the huge amount of data on the problem of OA, there is still no effective treatment that slows down the progression of the disease. Recently appeared monoclonal antibodies against nerve growth factor (NGF) as well as fibroblast growth factor (FGF)-18 may be the promising tool for clinical improvement of OAObjectivesTo evaluate the safety and efficacy of anti-NGF and FGF-18 on patients with osteoarthritis by a systematic review.MethodsIn the current study the search process was conducted in PubMed using the following strategy: “FGF-18” or “anti-NGF” and “OA”, “monoclonal antibody” + “osteoarthritis”. All articles published in the format of Case Reports, Clinical Study, Clinical Trial Protocol, Clinical Trial, Multicenter Study were reviewed. Clinical outcomes were assessed using clinical scores, included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain and Physical Function score, Patient’s Global Assessment of OA (PGA-OA), adverse events (AEs); cartilage repair and total femorotibial joint cartilage thickness were assessed using magnetic resonance imaging.ResultsBased on our search 23 publication were included in the study after omitting repetitions. Among 23 studies, 16 used anti-NGF monoclonal antibodies (Tanezumab, Fasinumab, Fulranumab), and 7 used recombinant human FGF-18 (Sprifermin). The total of 6679 patients were analysed in these articles.In the pooled analysis NGF inhibitors demonstrated statistically significant improvements compared with placebo in WOMAC Pain and Physical Function score (all studies revealed significantly better clinical outcomes in the anti-NGF group). After treatment with FGF-18 (Sprifermin) there was also improvement in WOMAC scores though not statistically significant. However, FGF-18 therapy was associated with the reductions in loss of total and lateral femorotibial cartilage thickness. Moreover, it does not only significantly reduce cartilage loss but also increase cartilage thickness. In terms of cartilage repair, 5 of 7 studies reported improvement in total femorotibial joint cartilage thickness.The AEs of FGF-18 or anti-NGF therapies were not serious, however they may affect the compliance and satisfaction of patients and clinicians. The proportion of patients with adverse events in anti-NGF treatment group was higher than that in FGF-18. The following conditions were reported in anti-NGF: abnormal peripheral sensation such as hypoesthesia (7.43%), paraesthesia (9.15%), hyperesthesia (0.36%), peripheral neuropathy and sensory disturbance (0.35%); arthralgia (15%), back pain (15.06%), pain in extremity (10%), headache (9.11%), upper respiratory tract infection (10.65%), diarrhoea (11.95%), sinusitis or nasopharyngitis (10.13%). The difference in AEs between sprifermin and placebo groups was found insignificant, most frequently reported event was arthralgia.ConclusionIn recent years significant progress has been achieved in search for pathogenetic therapy of OA. Based on the results of current research findings, NGF inhibitors relieved pain and enhance joint function and may be considered as the most effective for functional improvement. FGF-18 decrease the cartilage loss and may improve cartilage thickness. However, further clinical longitudinal studies characterised the risk-benefit are needed to establish their safety and efficacy.Disclosure of InterestsNone declared