In randomised controlled trials (RCTs), allergy immunotherapy (AIT) administered as SQ sublingual immunotherapy (SLIT)-tablets has shown to be an effective and well-tolerated treatment of allergic rhinitis due to grass, tree, ragweed, and house dust mite (HDM). Non-interventional studies (NISs) are conducted to further investigate effectiveness, safety, tolerability, adherence, and/or other aspects of authorised medicinal products in real-world clinical settings. This systematic literature review presents an overview of the totality of evidence from NISs with the SQ grass, tree, ragweed, and HDM SLIT-tablet.

Methods: PubMed, ClinicalTrials.gov, and EU Clinical Trials Register were screened for NISs with SQ grass, tree, ragweed, and HDM SLIT-tablets in June 2022 using the string ("Product Surveillance, Postmarketing"[MH] OR "post-marketing" OR "post-authorization" OR "cohort" or "case-control" OR "observational" OR "non-interventional" OR prospective OR "real-world" OR retrospective OR "drug utilization" OR longitudinal) AND (grazax OR itulazax OR ragwizax OR acarizax OR grastek OR itulatek OR ragwitek OR miticure OR odactra OR ALK[AD] OR ALK-abello[AD]) AND ("2006/01/01" [PDAT] : "2022/06/15"[PDAT]). Non-English, phase I-III trials, and publications prior to 2006 were excluded together with publications based on secondary data as well as cases, where it was unclear, if SQ SLIT-tablets were studied.

Of almost 150 screened publications, 21 publications based on 20 individual NISs with SQ grass, ragweed, and HDM SLIT-tablets were included (Table 1). The total study population consisted of 13,172 subjects (8,501 [65%] adults, 2,987 (23%) children, and 1,684 [13%] not specified). The publications included data from Europe (16 (76%]), North America (2 [10%]), and Asia (3 [14%]), and had clinical effectiveness (2 [10%]), quality of life/patient satisfaction (4 [19%]), safety/tolerability (12 [57%]), adherence (1 [5%]), or other (2 [10%]) as primary objective. Generally, the SQ SLIT-tablets improved symptoms and were well-tolerated. No NISs with the SQ tree SLIT-tablet were identified, likely explained by the treatment only being recently marketed.

The totality of real-world clinical evidence from NISs with the SQ grass, ragweed, and HDM SLIT-tablets is substantial and further complements the efficacy and safety profile established in RCTs. NISs studying clinical efficacy and safety of the SQ tree SLIT-tablet is warranted.