OBJECTIVES: Several monoclonal antibodies (mAb) are in development for the treatment of uncontrolled asthma. Network meta-analysis (NMA) will become unavoidable to compare effectiveness of these products. It could only be performed if studies define outcomes similarly. The objective of this research is to review the consistency of exacerbation definition used in clinical trials of mAb. METHODS: All mAbs approved or in phase II/III development in asthma were identified through a systematic review in Medtrack® database. Clinical trials were identified through the clinical.trials.gov registry. Exacerbation definition was searched for all identified trials through targeted literature search. Definitions were compared to the current European Respiratory Society, American Thoracic Society and Global Initiative for Asthma guidelines. RESULTS: Sixteen mAbs were identified in phase II/III development for asthma. Omalizumab is the only mAb approved for asthma and its pivotal trials occurred over 10 years ago. 95 clinical trials have been registered for these mAbs with 52 trials using exacerbation as a clinical endpoint.  Exacerbation definitions were retrieved for 25 trials, among which 40% of trials defined clinical or clinically relevant exacerbation, 12% defined severe exacerbations and 48% defined exacerbation without specification of severity or clinical relevance. Definitions used in trials were not aligned with current guideline definitions, and were inconsistent between studies.  Criteria used to define exacerbation included: rescue systemic corticosteroid, use of nebulization therapy, hospital or emergency room admission, unscheduled medical intervention, unscheduled outpatient visits, increased daily dose of rescue inhalers, worsening of symptoms, peak expiratory flow or FEV1 deterioration. CONCLUSIONS: High variability of outcome definitions suggests future hurdles for mAb to generate comparative effectiveness through NMA. Head-to-head comparison of the products reaching market in the next years is not expected, and health technology assessment around the extent of additional benefit might be challenging.