Steroid-sparing biologics in severe asthma and chronic obstructive pulmonary disease: a systematic review, cross-disease meta-analysis, and translational estimate of corticosteroid-related harm prevented.

BACKGROUND: Oral corticosteroids (OCS) remain widely used in uncontrolled severe asthma and frequently exacerbating chronic obstructive pulmonary disease (COPD), but cumulative exposure is associated with dose-dependent cardiovascular, metabolic, skeletal and infectious harm. Type-2 biologics may reduce OCS burden, although their clinical impact across asthma and COPD remains incompletely defined. METHODS: We conducted a PRISMA 2020 systematic review of MEDLINE, Embase, Cochrane Central Register. Eligible studies were randomized, placebo-controlled trials of monoclonal antibodies in adults with OCS-dependent severe asthma or moderate-to-severe COPD with documented OCS exposure. Risk of bias was assessed using RoB 2. Random-effects models estimated the odds ratio (OR) for achieving ≥50% maintenance OCS reduction in asthma and the rate ratio (RR) for moderate-to-severe exacerbations in both diseases, with disease as a pre-specified moderator. A translational module applied the 42% cumulative OCS reduction observed in the BOREAS/NOTUS COPD severe-exacerbation subgroup to dose-response hazard ratios from six pharmacoepidemiologic cohorts to estimate OCS-attributable adverse-event NNTs. RESULTS: Twenty-three studies were included. In severe asthma, biologics increased the odds of ≥50% maintenance OCS reduction (OR 2.99, 95% CI 2.11-4.25; I²=0%; four trials, n = 615). Exacerbation reduction favoured biologics in both diseases, but was greater in asthma than COPD (asthma RR 0.38, 95% CI 0.23-0.65; COPD RR 0.78, 95% CI 0.69-0.88; p = 0.0001). In COPD, translated NNTs were lowest for serious infection, pneumonia and osteoporotic fracture. CONCLUSIONS: Biologics provide robust OCS sparing in severe asthma and smaller but significant exacerbation reduction in COPD, with potential downstream harm reduction in high-burden COPD.