Comparative Efficacy and Acceptability of 12 Phosphorus-Lowering Drugs in Adults with Hyperphosphatemia and Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis

Background: Hyperphosphatemia is associated with cardiovascular morbidity and mortality in adults with chronic kidney disease (CKD). Drug therapy has an irreplaceable role in the management of hyperphosphatemia. Objectives: We aimed to compare and rank phosphorus-lowering drugs, including phosphate binder and nonphosphate binder, in hyperphosphatemia adults with CKD. Methods: We did a systematic review and frequentist random-effect network meta-analysis. We searched in PubMed, Cochrane Library, Web of Science, and Embase from inception to February 1, 2023, for randomized controlled trials of 12 phosphorus-lowering drugs in adults with hyperphosphatemia and CKD. Primary outcomes were efficacy (changes in serum phosphorus) and acceptability (treatment withdrawals due to any cause). We ranked each drug according to the value of surface under the cumulative ranking curve. We applied the Confidence in Network Meta-Analysis frameworks to rate the certainty of evidence. This study was registered with PROSPERO, number CRD42022322270. Results: We identified 2,174 citations, and of these, we included 94 trials comprising 14,459 participants and comparing 13 drugs or placebo. In terms of efficacy, except for niacinamide, all drugs lowered the level of serum phosphorus compared with placebo, with mean difference ranging between −1.61 (95% credible interval [CrI], −2.60 to −0.62) mg/dL for magnesium carbonate and −0.85 (−1.66 to −0.05) mg/dL for bixalomer. Only ferric citrate with odds ratios 0.56 (95% CrI: 0.36–0.89) was significantly associated with fewer dropouts for acceptability. Of the 94 trials, 43 (46%), 7 (7%), and 44 (47%) trials were rated as high, moderate, and low risk of bias, respectively, the certainty of the evidence was moderate to very low. Conclusions: Magnesium carbonate has the best phosphorus-lowering effect in hyperphosphatemia adults with CKD; considering efficacy and acceptability, ferric citrate shows evidence to be the most appropriate drug with or without dialysis.