Dear Editor,
We read with interest the recent meta-analysis by Di Bona et al published in the World Allergy Organization Journal concluding that the 300 IR 5-grass pollen sublingual immunotherapy (SLIT) tablet provides significant clinical benefits, with a reported mean difference (MD) of −1.26 (95% CI −1.64 to −0.89).1 While the intent to analyze specific products individually rather than assuming a generic “class effect” is commendable, a careful examination of the methodology reveals significant inconsistencies compared with previous landmark meta-analyses on the same topic.
It is well established that no new randomized controlled trials (RCTs) on this specific Stallergenes product have been published since 2015. However, the conclusions of the current study diverge substantially from those reported in the comprehensive meta-analysis published in JAMA Internal Medicine in 2015 by Di Bona, Di Lorenzo et al2 and the network meta-analysis by Nelson et al.3
In the 2015 analysis,2 ALK/Merck and Stallergenes products were compared without aggregation. That study reported a more modest MD of 0.83 (95% CI 0.63–1.03) and found no statistically significant difference between the 2 commercial products. The fundamental difference between the “modest” efficacy reported in 2015 and the “high” efficacy claimed in 2024 does not stem from new evidence, but rather from a retrospective modification of inclusion criteria.
Specifically, the current analysis includes the study by Horak et al, a chamber challenge study. In the 2015 meta-analysis,2 the same first author (Di Bona) rigorously excluded this study. The rationale was methodologically sound: chamber challenge studies operate under controlled, high-exposure conditions that do not reflect the natural variability of field trials and are generally recognized as potentially overestimating treatment efficacy compared with real-world settings.
By reintroducing the Horak study into a small pool of only 4 RCTs (alongside Didier, Cox, and Wahn), the statistical weight of this single chamber challenge study disproportionately inflates the overall efficacy estimate. It raises methodological questions that a study deemed unsuitable for inclusion in 2015 due to design heterogeneity now becomes a cornerstone of the 2024 findings, effectively shifting the result from “statistically significant but modest” to “clinically relevant."
We believe that transparency in meta-analytic methodology is essential for the integrity of evidence-based medicine. When inclusion criteria change between analyses conducted by overlapping author groups without the addition of new primary data, the scientific community deserves a clear explanation of the rationale underlying such methodological shifts.
We respectfully invite the authors to clarify the scientific justification for including the Horak chamber study in the current analysis when it was explicitly excluded from the 2015 meta-analysis by the same lead author, particularly given that no new RCTs have emerged in the intervening years.
Funding
None.
Authors’ contributions
Gabriele Di Lorenzo and Marcello Melluso both contributed to the submitted text.
Conflicts of interest
The authors declare no conflicts of interest.
Footnotes
Full list of author information is available at the end of the article
References
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