Abstract
Background
We aimed to evaluate the predictors of sustainability of biologic drugs for paediatric patients with Crohn’s disease (CD).
Methods
The Czech National Prospective Registry of Biologic and Targeted Therapy of Inflammatory Bowel Disease (CREdIT) was used to identify the biologic treatment courses in paediatric patients with CD. Mixed-effects Cox models and propensity score analyses were employed to evaluate predictors of treatment sustainability.
Results
Among the 558 observations of 473 patients, 264 were treated with adalimumab (47%), 240 with infliximab (43%), 41 with ustekinumab (7%), and 13 with vedolizumab (2%). Multivariable analysis revealed higher discontinuation risk with infliximab compared to adalimumab (HR = 0.600, 95%CI 0.389–0.926), both overall and in first-line treatment (HR = 0.302, 95%CI 0.103–0.890). Infliximab versus adalimumab was associated with shorter time to escalation (HR = 0.094, 95%CI 0.043–0.203). Propensity-score analysis demonstrated lower sustainability of infliximab (HR = 0.563, 95%CI 1.159–2.725). The time since diagnosis to treatment initiation (HR = 0.852, 95%CI 0.781–0.926) was the most important predictor. Baseline immunosuppressive therapy prolonged sustainability with infliximab (HR = 2.899, 95%CI 1.311–6.410).
Conclusions
Given the results suggesting shorter sustainability, the need for earlier intensification and thus higher drug exposure, and the greater need for immunosuppression with infliximab than with adalimumab, the choice of these drugs cannot be considered completely equitable.
Impact
-
Our study identified predictors of sustainability of biologic treatment in paediatric patients with Crohn’s disease, including adalimumab (versus infliximab), early initiation of biologic treatment, and normalised baseline haemoglobin levels. Infliximab treatment was associated with earlier intensification, higher drug exposure, and a greater need for immunosuppression.
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Parents and patients should be fully informed of the disadvantages of intravenous infliximab versus adalimumab during the decision-making process.
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This study emphasises the importance of not delaying the initiation of biologic therapy in paediatric patients with Crohn’s disease.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We would like to thank Editage (www.editage.com) for English language editing. We would also like to thank Institute of Biostatistics and Analyses for operating the CREDIT Registry. This work was supported by the Grant Agency of Charles University in Prague (grant number 227023) and the Ministry of Health, Czech Republic, for the conceptual development of the research organisations (00064203, University Hospital Motol, Prague, Czech Republic).
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Contributions
O.H.: Created the conception, study design and data analysis, patient recruitment, first draught of the paper. I.C.: Patient recruitment and revision of the original article. M.D.: Patient recruitment and revision of the original article. D.K.: Patient recruitment and revision of the original article. T.L.: Patient recruitment and revision of the original article. K.M.: Patient recruitment and revision of the original article. J.S.: Patient recruitment and revision of the original article. R.V.: Patient recruitment and revision of the original article. N.L.: Patient recruitment and revision of the original article. E.K.: Patient recruitment and revision of the original article. M.V.V.: Patient recruitment and revision of the original article. A.S.: Patient recruitment and revision of the original article. L.G.: Patient recruitment and revision of the original article. M.V.: Patient recruitment and revision of the original article. I.Z.: Patient recruitment and revision of the original article. M.Z.: Patient recruitment and revision of the original article. M.B.: Leading the registry, patient recruitment and revision of the original article. J.B.: Leading the project team, patient recruitment and revision of the original article.
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O.H.: lectures/congress fees/consultancy (outside the scope of the submitted work; MSD, AbbVie, Takeda, Sandoz, Nutricia, Nestlé, and Ferring). I.C.: no conflict. M.D.: congress fees (outside the scope of the submitted work; Nutricia, Nestlé). D.K.: congress fee (outside the scope of the submitted work; Takeda). T.L.: lectures/congress fees/consultancy (outside the scope of the submitted work; Ferring, Nutricia, Biocodex, and AbbVie). K.M.: lectures/congress fees/consultancy (outside the scope of the submitted work; Takeda, Janssen-Cilag). J.S.: lectures/congress fees (AstraZeneca, AbbVie, Nestlé, Nutricia, MSD, and Takeda). R.V.: congress fees (outside submitted work; AbbVie, Nestlé). N.L.: lectures/congress fees/consultancy (outside the scope of the submitted work; AbbVie, Sandoz, Nutricia, Nestlé). E.K.: lectures/congress fees/consultancy (outside the scope of the submitted work; AbbVie, Nutricia, and Nestlé). M.V.V.: lectures, congress fees (outside submitted work) - Nestlé, Nutricia. A.S.: Lectures/congress fees/consultancy —AbbVie, Takeda, Nutricia, Nestlé. L.G.: no conflict. M.V.: no conflict. I.Z.: no conflict. M.Z.: no conflict. M.B.: lectures/congress fees/consultancy (outside the scope of the submitted work; Abbvie, Takeda, Janssen-Cilag, Celltrion, Roche, AstraZeneca, Biogen, Tillotts, Ferring, Alfasigma, PRO.MED.CS, Sandoz, Bristol-Myers Squibb, Pfizer, and Swedish Orphan Biovitrum). J.B.: lectures/congress fees/consultancy (outside the scope of the submitted work; MSD, AbbVie, Sandoz, Danone-Nutricia, and Nestlé).
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This study was approved by the Ethics Committee (EK - 440/30) and all parents or participants provided informed consent.
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Hradsky, O., Copova, I., Durilova, M. et al. Sustainability of biologic treatment in paediatric patients with Crohn’s disease: population-based registry analysis. Pediatr Res (2023). https://doi.org/10.1038/s41390-023-02913-7
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DOI: https://doi.org/10.1038/s41390-023-02913-7
