What is the role of immunomodulators in children with allergic bronchopulmonary aspergillosis and asthma? A systematic review of the literature and evidence-based guideline recommendation

Background: Allergic Bronchopulmonary Aspergillosis (ABPA) is a complex allergic disorder complicating asthma and cystic fibrosis. Steroids and antifungal agents are the mainstay of ABPA treatment. But almost half the patients relapse on tapering the steroids and some become steroid dependent, requiring continuous oral steroids. Therefore, immunomodulators targeting Th2 inflammation are being tried for treating ABPA. Objective: This systematic review was undertaken to evaluate the efficacy of immunomodulators for ABPA in children asthma, to develop an evidence-based recommendation. The research question was: In children with asthma having ABPA, what is the efficacy and safety of therapy with biologicals (compared with not using biologicals), on multiple clinical outcomes? Methods: A search for pre-existing guidelines and systematic reviews yielded no relevant results. We, therefore, undertook a new systematic review of randomised controlled trials (RCTs), addressing the question. Results: We identified only two small RCTs, in ABPA complicating asthma. The first evaluated omalizumab, and the other was a conference abstract on dupilumab. Both trials had methodological limitations, and evidence was graded as ‘very low certainty’. Neither trial suggested any benefit of using immunomodulators in those with asthma, having ABPA. Conclusion: We recommend against immunotherapy with biologicals including omalizumab or dupilumab in children with asthma and ABPA (conditional recommendation, very low certainty of evidence).