Efficacy and safety of anti-interleukin-1 therapeutics in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials

Abstract

Objective We aimed to evaluate the efficacy and safety of anti-interleukin-1 therapeutics, including IL-1 antibodies, interleukin-1 receptor antagonists (IL-1 Ras) and IL-1 inhibitors, for knee osteoarthritis (KOA) treatment. Methods Databases (Medline, Embase, Web of Science and CENTRAL) and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) of anti-interleukin-1 therapeutics from inception to August 31, 2022. The outcomes were the mean change in pain and function scores and the risk of adverse effects (AEs). Results In the 12 studies included, anti-interleukin-1 therapeutics were superior to placebo in terms of pain relief (standardized mean difference [SMD] = − 0.38, 95% confidence interval [CI] = − 1.82 to − 0.40, p < 0.001, I2 = 77%) and functional improvement (SMD = − 1.11, 95% CI = − 1.82 to − 0.40, p = 0.002, I2 = 96%). The incidence of any AE (risk ratio [RR] = 1.02, 95% CI = 0.88–1.18, p < 0.001, I2 = 76%) was higher following treatment with anti-interleukin-1 therapeutics than placebo, while no significant difference was found in the incidence of serious AEs (SAEs) or discontinuations due to AEs. Subgroup analyses showed that IL-1 antibodies and the IL-1 inhibitor provided pain relief (IL-1 antibodies: SMD = − 0.61, 95% CI = − 0.92 to − 0.31, p < 0.001; IL-1 inhibitor: SMD = − 0.39, 95% CI = − 0.72 to − 0.06, p = 0.02, I2 = 74.0%) and functional improvement (IL-1 antibodies: SMD = − 1.75, 95% CI = − 2.10 to − 1.40, p < 0.001; IL-1 inhibitor: SMD = − 0.28, 95% CI = − 0.83 to 0.27, p = 0.31, I2 = 88%) superior to those of placebo, whereas IL-1 Ras did not. However, the IL-1 inhibitor increased the incidence of any AE (RR = 1.35, 95% CI = 0.92–1.98, p < 0.001, I2 = 85%) but not the risk of SAEs or discontinuations due to AEs. IL-1 antibodies and IL-1 Ras showed no difference in safety compared with placebo. Conclusions Anti-interleukin-1 therapeutics could relieve OA-related pain and improve function, but is probably associated with an increased risk of adverse events. Specially, IL-1 antibodies and an IL-1 inhibitor could relieve OA-related pain and improve function, whereas IL-1 Ras could not. IL-1 antibodies and IL-1 Ras were relatively safe options, but IL-1 inhibitors were associated with safety concerns.

Efficacy of Anti-Interleukin-1 Therapeutics in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials from the Years 2000 to 2023

“…Our results are parallel to those from the meta-analysis made by Lizhi Yu et al in February 2023 [6]. However, there are two-fold main differences between our meta-analyses.…”

“…Beginning the work on this meta-analysis, we found four meta-analyses with similar themes published in the years 2019-2023 [6,[11][12][13]. However, the meta-analyses published so far have not included the most recent studies.…”

“…Currently, standard treatment approaches contain a wide range of oral medications embracing nonsteroidal anti-inflammatory drugs (NSAIDs) (as a first-line treatment), opioids, steroids and hyaluronic acid (HA) [6]. However, the prolonged use of nonsteroidal anti-inflammatory drugs or corticosteroids can lead to a series of side effects and limited therapeutic efficacy.…”

Effects of Terpenes on the Osteoarthritis Cytokine Profile by Modulation of IL-6: Double Face versus Dark Knight?

“…IL-1 family members are the most highly profiled in OA and have all been shown to be present in the synovial fluid and subchondral bone of OA patients [ 42 ]. IL-1β is also actively involved in the pathogenesis of cartilage loss related to OA [ 43 ]. The low levels of IL-1β induced by the local inflammatory process in KOA [ 44 ] were further reduced by hemp seed oil and terpenes, which therefore demonstrated their synergic anti-inflammatory action.…”