Benefits and harms of aspirin desensitization for aspirin-exacerbated respiratory disease: a systematic review and meta-analysis

Background: Aspirin desensitization is increasingly recommended for the treatment of aspirin-exacerbated respiratory disease (AERD). The objective of this study is to systematically review the efficacy and safety of aspirin desensitization in patients with AERD. Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception to January 5, 2019. We included randomized trials and comparative observational studies in any language. Data extraction and risk of bias assessment were performed in duplicate independently. Results: Five randomized controlled trials (RCTs) enrolled 233 patients with AERD. Compared to placebo, aspirin desensitization (mean daily dose 800 mg) improved quality of life (risk ratio [RR] 2.00; 95% confidence interval [CI], 1.31 to 3.06; heterogeneity measure [I²] = 0%; risk difference [RD] +24%; 22-item Sino-Nasal Outcome Test [SNOT-22] scale [0 to 110, higher worse]; mean difference [MD] −10.27 [95% CI, −6.39 to −14.15]; moderate-certainty); and respiratory symptoms (RR 2.20 [95% CI, 1.55 to 2.73], I² = 34%, RD +36%; American Academy of Otolaryngology (AAO) scale [0 to 20, higher worse]; MD −2.56 [95% CI,−1.12 to −3.92]; high-certainty). Aspirin desensitization increased adverse events severe enough to cause treatment discontinuation (major bleeding, gastritis, asthma exacerbation, or rash causing drug discontinuation, RR 4.39 [95% CI, 1.43 to 13.50], I² = 0%, RD +11%, moderate-certainty), and gastritis (RR 3.84 [95% CI, 1.12 to 13.19], I² = 0%, RD +9%, low-certainty). Findings were robust to sensitivity analyses. Two available observational studies were not informative because they lacked adjustment for confounders and/or contemporaneous controls. Conclusion: In patients with AERD, moderate-certainty and high-certainty evidence shows that aspirin desensitization meaningfully reduces symptoms of rhinosinusitis and improves quality of life, but results in a significant increase in adverse events.