Drug hypersensitivity in the fast lane: What clinicians should know about phenotypes, endotypes, and biomarkers.

Abstract Background Inhaled corticosteroids (ICS) are recommended as the first-line controller medications for persistent asthma. However, guidelines on the initial ICS doses, “stepup” and “step-down” algorithms, and when to switch to combination therapy vary. Objective: To understand the ideal starting doses of ICS therapy based on current evidence, and to systematically compare low, moderate, and high starting doses of ICS as monotherapy and in combination with long-acting b-agonists (LABA) with respect to efficacy and safety. Methods Medline, Embase, and Cochrane databases were searched for relevant English articles published from 1980 to November 17, 2018. Randomized controlled trials (RCTs) with adult, steroid-naive/ICS-free (for ≥4 weeks) patients with asthma with ≥4 weeks duration with an ICS-treatment arm (mono or combination therapy) were included. Separate fixed-effects Bayesian network meta-analyses were conducted on the extracted data for peak expiratory flow [PEF], forced expiratory volume in 1 second [FEV1], nighttime rescue medication use, nighttime symptom score, and study withdrawal due to an adverse event [AE]. Results Thirty-one RCTs were analyzed. All starting doses of ICS were comparable with respect to nighttime rescue medication use, nighttime symptom score, change in FEV1, and study withdrawal due to an AE. Significant improvement in morning PEF was observed with high-dose ICS and with low- and moderate-dose ICS/LABA over low-dose ICS. Conclusion Overall, a high starting dose of ICS had no additional clinical benefit in 3 of the 4 efficacy parameters relative to low or moderate ICS doses for controlling moderate to severe asthma, but might have potential safety concerns.