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.

Abstract

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. 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. 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. 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.