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

ObjectiveWe 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.MethodsDatabases (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).ResultsIn 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, I-2 = 77%) and functional improvement (SMD = - 1.11, 95% CI = - 1.82 to - 0.40, p = 0.002, I-2 = 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, I-2 = 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, I-2 = 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.ConclusionsAnti-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.