BACKGROUND & AIMSNo meta-analysis has analysed efficacy and safety of long-acting growth hormone (GH) therapy in adult GH deficiency. We undertook this meta-analysis to address this gap in knowledge METHODS: Electronic databases were searched for RCTs involving adult GH deficiency patients receiving weekly long-acting GH as compared to daily GH/placebo controls. Primary outcome was to evaluate changes in body-composition parameters. Secondary outcomes were to evaluate alterations in glycaemia and adverse-events.RESULTSData from 5 studies involving 648 patients were analysed (4 studies having daily GH as active controls; 1 study having placebo as passive controls). Over 24-34 weeks clinical use, patients receiving long-acting GH had comparable change in lean mass [MD-0.28 kg (95%CI: 0.94 - 0.38); P = 0.41; I² = 29% (low heterogeneity)] and fat mass [MD-0.10 kg (95%CI: 1.97-1.78); P = 0.92; I² = 77%(considerable heterogeneity)] as compared to daily GH injections. Long-acting GH use was associated with significantly lower visceral adipose tissue [MD-1.75 cm²(95%CI: 2.14 to -1.35); P < 0.01; I² = 0% (low heterogeneity)] and higher gynoid fat-mass [MD 0.14 kg(95%CI:0.02-0.26); P = 0.03] compared to daily GH injections. Total adverse events [Risk ratio (RR) 1.65 (95% CI: 0.83-3.29); P = 0.15; I² = 68%] and severe adverse events [RR 0.60 (95% CI: 0.30-1.19); P = 0.14; I² = 0%] were not significantly different in long-acting GH group compared to controls. Occurrence of headache, arthralgia, nasopharyngitis, new onset diabetes, anti-GH antibodies were comparable among groups. Long-acting GH users had significantly higher treatment adherence compared to controls [OR 4.80 (95%CI:3.58-6.02); P < 0.01; I² = 0%].CONCLUSIONLong-acting GH has comparable beneficial impact on body composition parameters in adult GH deficiency, is well tolerated without any increased adverse events.

01 Jan 2022·Journal of CancerQ3 · MEDICINE

An insulin growth factor-I/II-neutralizing monoclonal antibody in combination with epidermal growth factor receptor inhibitors potently inhibits tumor cell growth

Q3 · MEDICINE

ArticleOA

Author: Wang, Liping ; Dimitrov, Dimiter S ; Shan, Yaming ; Zhao, Qi ; Tan, Chengyue ; Wang, Feng ; Shao, Ningyi ; Ma, Guofang

The insulin-like growth factors (IGFs), IGF-1 and IGF-II, which bind to the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), have been implicated in the growth, survival, and metastasis of tumor cells. We have previously identified a novel human monoclonal antibody (mAb), m708.5, which neutralizes both human IGF-I and IGF-II, and potently inhibits phosphorylation of the IGF-1R and the IR in breast cancer cells. In this study, m708.5 exhibited very strong synergy with the epidermal growth factor receptor (EGFR) inhibitor gefitinib, and synergy with chemotherapeutic agents in vitro against either neuroblastoma or breast cancer cells. In xenografted models, the combination of m708.5 and gefitinib significantly inhibited LAN-1 cell growth better than single agent alone. Taken together, these results support the clinical development of m708.5 for solid tumors with potential for synergy with chemotherapy and EGFR inhibitors.

21 May 2021·Pain MedicineQ3 · MEDICINE

The Effectiveness of Anti-Nerve Growth Factor Monoclonal Antibodies in the Management of Pain in Osteoarthritis of the Hip and Knee: A PRISMA Systematic Review and Meta-Analysis

Q3 · MEDICINE

Review

Author: Rammanohar, Jashmitha ; To, Kendrick ; Khan, Wasim S ; Sutton, James ; Seah, K T Matthew

AbstractObjectiveTo conduct a systematic review and meta-analysis of the efficacy of anti-nerve growth factor (NGF) monoclonal antibodies in osteoarthritis pain (hip and knee).DesignGrade the evidence for anti-NGF use.MethodsAn interdisciplinary work group conducted a literature search for anti-NGF use in osteoarthritis. The systematic review was performed in accordance with methods described by the Cochrane collaboration. General inclusion criteria included all osteoarthritis trials studying any monoclonal anti-NGF antibody at any dose/phase. Excluded studies were those where participants received NSAIDs or analgesics other than anti-NGF antibodies. The Jadad Scale score was used to assess the quality of the included studies.ResultsThirteen studies were included in the analysis, involving 8145 participants with a diagnosis of hip and/or knee osteoarthritis. Anti-NGF antibody treatment was associated with a significant improvement in all Western Ontario and McMaster Universities Arthritis Index (WOMAC) indices when compared to placebo. These agents were not associated with a significantly increased incidence of serious adverse events but were associated with significant increases in therapy discontinuation due to adverse events or side effects (e.g., peripheral neuropathy).ConclusionsFuture randomized clinical trials are needed to characterize the overall risk-to-benefit ratio of anti-NGF antibodies in managing pain associated with OA, particularly with long-term use, in order to verify their efficacy and safety in clinical practice.

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