Impact of using less objective symptoms to define tolerated dose during food challenges: A data-driven approach - 05/07/23
, Nandinee Patel, MRCPCH, PhD a, Katharina Blumchen, MD b, Stefanie Berkes, BSc a, Hugh A. Sampson, MD c, Kirsten Beyer, MD dAbstract |
Background |
Food challenges (FCs) form the basis for assessing efficacy outcomes in interventional studies of food allergy; however, different studies have used a variety of similar but not identical criteria to define a challenge reaction, including subjective (nonobjective) symptoms occurring in a single-organ system as dose limiting.
Objective |
Our aim was to undertake a secondary analysis of 4 interventional studies to assess the impact of using less objective criteria to determine challenge-stop on reaction thresholds and their reproducibility.
Methods |
We analyzed individual participant data, including individual participant data meta-analysis, by using 3 different published challenge-stop criteria: (1) PRACTALL consesus criteria; (2) Consortium for Food Allergy Research version 3 (CoFAR v3) with at least 1 moderate- or severe-grade symptom; or (3) CoFAR v3 with at least 2 mild symptoms occurring in different organ systems. Reproducibility of challenge threshold was also assessed in participants undergoing subsequent repeat FCs.
Results |
Four studies, with detailed challenge data from a total of 592 participants, were included. Applying CoFAR v3 definitions for dose-limiting symptoms resulted in an underestimate of reaction thresholds compared with those in PRACTALL (P < .001) that is equivalent to almost a single dosing increment when using a semi-log dosing regimen. Reproducibility was also reduced when applying CoFAR v3 (P < .001 [n = 223]). Using the least conservative interpretation of CoFAR v3 (≥2 mild symptoms occurring in different systems) resulted in a significant overestimate of 15% when assessing oral immunotherapy efficacy. Applying a data-driven minor modification to CoFAR v3 resulted in a new set of challenge-stop criteria with validity similar to that of PRACTALL but one that is simpler to implement and in which significant gastrointestinal discomfort with observable decreased activity remains a dose-limiting symptom.
Conclusion |
The use of less objective symptoms to define challenge-stop compromises the reproducibility of the FC as a tool to assess efficacy outcomes in interventional studies, and potentially overestimates the efficacy of the intervention tested.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : CoFAR, eliciting dose, food challenge, peanut, PRACTALL, reproducibility, thresholds
Abbreviations used : CoFAR, DBPCFC, DLS, FC, OIT
Plan
| Supported by the UKMedical Research Council (award MR/S036954/1 [to P.J.T.]), National Institute for Health and Care Research/Imperial Biomedical Research Ccntre (to P.J.T.), and JM Charitable Foundation (to P.J.T.). |
|
| Disclosure of potential conflict of interest: P. J. Turner reports personal fees from the UK Food Standards Agency, Aimmune Therapeutics, Allergenis, Aquestive Therapeutics, and Novartis. K. Blumchen reports consulting for Aimmune Therapeutics, DBV Technologies, Bencard Allergie, Novartis; speakers bureau for Aimmune Therapeutics, DBV Technologies, HAL Allergy, Nutricia, ALK, Allergopharma, Nestle, and Novartis; and research grants from Aimmune Therapeutics, DBV Technologies, Novartis and Hipp, outside the submitted work. H.A. Sampson reports advisory board/consulting fees DBV Technologies, N-Fold, and Siolta Therapeutics; grant funding from the National Institutes of Health/National Institute of Allergy and Infectious Diseases; and royalties from Elsevier. K. Beyer reports advisory board/consulting fees from Aimmune Therapeutics, Allergy Therapeutics, Bencard, Danone, DBV, Hipp, Hycor, Jenapharm, Mylan/Meda Pharma/Mice, and Nestle; speakers bureau for Aimmune Therapeutics, ALK, Danone, Infectopharm, Med Update, Nestle, Nutricia; and research grants from Aimmune, ALK, Danone, DBV, Hipp, Hycor, Infectopharm, and Nutricia, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 152 - N° 1
P. 145-154 - juillet 2023 Retour au numéro
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