Is Lutikizumab, an Anti–Interleukin-1α/β Dual Variable Domain Immunoglobulin, efficacious for Osteoarthritis? Results from a bayesian network meta-analysis

Abstract

Objective. Most guidelines recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol for the nonoperative treatment of osteoarthritis (OA), but the use of them is limited by the tolerability and safety concerns. Lutikizumab is a novel anti–IL-1α/β dual variable domain immunoglobulin that can simultaneously bind and inhibit IL-1α and IL-1β to relieve the pain and dysfunction symptoms. We conducted this network meta-analysis to comprehensively compare the clinical efficacy and safety of lutikizumab with other drugs recommended by guidelines. Methods. We conducted a Bayesian network and conventional meta-analyses to compare the efficacy and safety of lutikizumab with other traditional drugs. All eligible randomized clinical trials, in PubMed, CNKI, EMBASE, and Web of Science databases, from January 2000 to January 2020, were included. The Cochrane risk of the bias assessment tool was used for quality assessment. Pain relief, function improvement, and risk of adverse effects (AEs) were compared in this study. Results. 24 articles with 11858 patients were included. Duloxetine (DUL) had the largest effect for pain relief (4.76, 95% CI [2.35 to 7.17]), and selective cox-2 inhibitors (SCI) were the most efficacious treatment for physical function improvement (SMD 3.94, 95% CI [2.48 to 5.40]). Lutikizumab showed no benefit compared with placebo for both pain relief (SMD 1.11, 95% CI [-2.29 to 4.52]) and function improvement (SMD 0.992, 95% CI [-0.433 to 4.25]). Lutikizumab and all other drugs are of favorable tolerance for patients in the treatment of OA compared with placebo. Conclusions. Lutikizumab, the new anti–Interleukin-1α/β dual variable domain immunoglobulin, showed no improvement in pain or function when compared with placebo. Selective cox-2 inhibitors and duloxetine remain the most effective and safest treatment for OA. More high-quality trials are still needed to reconfirm the findings of this study.

Efficacy and safety of biologic agents for the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials

“…As for IL-1 inhibitors and TNF-α inhibitors, there were two published studies evaluating the efficacy and safety of these two in OA. 30 , 31 Persson et al 30 reported that the efficacy of biologic disease-modifying anti-rheumatic drugs, IL-1 inhibitors and TNF-α inhibitors, was not superior to placebo in the treatment of OA. It is noteworthy that this meta-analysis included six related RCTs and contained four kinds of IL-1 inhibitors and TNF-α inhibitors (adalimumab, etanercept, anakinra, and infliximab) without inclusion of the other three inhibitors (i.e.…”

“…lutikizumab, AMG 108, and canakinumab). Another meta-analysis conducted by Cao et al 31 only evaluated the efficacy and safety of lutikizumab, an anti–IL-1α/β dual-variable domain immunoglobulin, and only included two RCTs of lutikizumab. Lutikizumab showed no improvement either in pain or function, but was of fine tolerance for patients with OA.…”

“… 26 – 29 Contrary to the results of NGF inhibitors, two meta-analyses evaluated the efficacy of IL-1 inhibitors and TNF-α inhibitors, and ended up with conclusions of ineffectiveness for OA. 30 , 31 Nevertheless, despite the increase of relevant clinical trials, no comprehensive meta-analysis has been undertaken to date to evaluate the efficacy and safety of these three main cytokine blockers in the treatment of OA. Therefore, the present meta-analysis was intended to examine the efficacy and safety of biologic agents based on the current RCTs investigating NGF inhibitors, IL-1 inhibitors, and TNF-α inhibitors.…”

Neuroimmune interactions in painful TMD: Mechanisms and treatment implications

“…108 Lutikizumab, the new anti-IL-1α/β dual variable domain immunoglobulin, did not improve pain or function in the comparison with placebo. 109 However, autologous conditioned serum (ACS) as a source of IL-1 receptor antagonist (IL-1Ra) promotes the repair of cartilage and subchondral bone of the knee joint and is an alternative therapy for degenerative joint disease of the knee; but, no reports exist on the use of ACS in the TMJ. 110 Although IL-1 inhibitor shows its effectiveness for OA treatment in numerous preclinical studies, its failure to improve OA compared to placebo control in clinical trials warrants further investigation of the mechanisms of action and refinement of treatment regimen.…”

Relative Efficacy and Safety of Anti-Inflammatory Biologic Agents for Osteoarthritis: A Conventional and Network Meta-Analysis

“…For example, Fleischmann et al [ 8 ] suggested that lutikizumab use significantly relieved pain compared with placebo, while Kloppenburh et al [ 9 ] reported that lutikizumab did not alleviate pain or imaging outcomes in comparison to placebo. Moreover, previous systematic reviews also indicated the inconsistent efficacy of biologic agents [ 10 , 11 , 12 ]. Therefore, we performed an up-to-date network meta-analysis to compare the efficacy and safety of biologics targeting inflammation among OA patients.…”