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Effectiveness and Safety of Adalimumab, Etanercept and Ustekinumab for Severe Psoriasis in Children Under 12 Years of Age: A French-Italian Daily Practice Cohort (BiPe Jr)

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Abstract

Introduction

Biological therapies are valuable treatments for severe psoriasis. Children aged under 12 years are underrepresented in therapeutic trials for these drugs. The objective of the ‘BiPe Jr’ cohort study was to evaluate the drug survival, effectiveness, tolerance and switching patterns of biological therapies in children under 12 years of age with psoriasis.

Methods

We conducted a multicentre retrospective study of children with psoriasis who received at least one injection of a biological agent, even off-licence, before the age of 12 years in France and Italy, collecting the data between April and August 2021. The data collected were from March 2012 up to August 2021.

Results

In total, 82 children (mean age: 9.1 years; females: 61.0%) received 106 treatments. The drugs administered were adalimumab (n = 49), etanercept (n = 37), ustekinumab (n = 15), anakinra (n = 2), infliximab (n = 2) and secukinumab (n = 1). The most common form of psoriasis was plaque psoriasis (62.9%). The Physician Global Assessment and the Psoriasis Area Severity Index (PASI) scores decreased significantly from baseline to 3 months after treatment initiation for the three main biological drugs; PASI went from 14.1 ± 9.4 to 4.1 ± 11.3 for adalimumab (p = 0.001), 14.9 ± 9.3 to 5.1 ± 4.0 for etanercept (p = 0.002) and 11.6 ± 8.3 to 2.6 ± 2.2 for ustekinumab (p = 0.007). A trend towards higher 2-year maintenance rates was observed for ustekinumab and adalimumab, compared with etanercept (p = 0.06). 52 children discontinued their biological therapy, most frequently due to inefficacy (n = 28) and remission (n = 14). Seven serious adverse events (SAEs) were reported, including four severe infections.

Discussion

Our analyses of drug survival and treatment patterns, combined with those of previous studies conducted in older children, indicate that there is a trend towards higher 2-year survival rates of ustekinumab and adalimumab. The SAEs identified were rare, but highlight the need for increased vigilance concerning infections. Overall, the biological therapies showed good effectiveness and safety profiles when used in daily practice for the treatment of young children with psoriasis.

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References

  1. Nast A, Gisondi P, Ormerod AD, et al. European S3—guidelines on the systemic treatment of psoriasis vulgaris—update 2015–Short version—EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2015;29:2277–94.

    Article  CAS  Google Scholar 

  2. Mahé E, Amy-De La-Bretêque M, Phan C. Perspectives on the pharmacological management of psoriasis in pediatric and adolescent patients. Expert Rev Clin Pharmacol. 2021;14:807–19.

    Article  Google Scholar 

  3. Menter A, Cordoro KM, Davis DMR, et al. Joint American academy of dermatology-national psoriasis foundation guidelines of care for the management and treatment of psoriasis in pediatric patients. J Am Acad Dermatol. 2020;82:161–201.

    Article  Google Scholar 

  4. Eisert L, Augustin M, Bach S, et al. S2k guidelines for the treatment of psoriasis in children and adolescents—short version part 2. J Dtsch Dermatol Ges. 2019;17:959–73.

    PubMed  Google Scholar 

  5. Fortina AB, Bardazzi F, Berti S, et al. Treatment of severe psoriasis in children: recommendations of an Italian expert group. Eur J Pediatr. 2017;176:1339–54.

    Article  CAS  Google Scholar 

  6. Charbit L, Mahé E, Phan A, et al. Systemic treatments in childhood psoriasis: a French multicentre study on 154 children. Br J Dermatol. 2016;174:1118–21.

    Article  CAS  Google Scholar 

  7. Bronckers IMGJ, Seyger MMB, West DP, et al. Safety of systemic agents for the treatment of pediatric psoriasis. JAMA Dermatol. 2017;153:1147–57.

    Article  Google Scholar 

  8. Mahé E, Corgibet F, Maccari F, et al. Prescriptions hors AMM (autorisation de mise sur le marché) dans le psoriasis de l’enfant. Ann Dermatol Venereol. 2020;147:429–38.

    Article  Google Scholar 

  9. Paller AS, Siegfried EC, Langley RG, et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med. 2008;358:241–51.

    Article  CAS  Google Scholar 

  10. Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad Dermatol. 2015;73:594–603.

    Article  CAS  Google Scholar 

  11. Papp K, Thaçi D, Marcoux D, et al. Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial. Lancet. 2017;390:40–9.

    Article  CAS  Google Scholar 

  12. Bodemer C, Kaszuba A, Kingo K, et al. Secukinumab demonstrates high efficacy and a favourable safety profile in paediatric patients with severe chronic plaque psoriasis: 52-week results from a Phase 3 double-blind randomized, controlled trial. J Eur Acad Dermatol Venereol. 2021;35:938–47.

    Article  CAS  Google Scholar 

  13. Philipp S, Menter A, Nikkels AF, et al. Ustekinumab for the treatment of moderate-to-severe plaque psoriasis in paediatric patients (≥ 6 to < 12 years of age): efficacy, safety, pharmacokinetic and biomarker results from the open-label CADMUS Jr study. Br J Dermatol. 2020;183:664–72.

    Article  CAS  Google Scholar 

  14. Phan C, Beauchet A, Burztejn AC, et al. Biological treatments for paediatric psoriasis: a retrospective observational study on biological drug survival in daily practice in childhood psoriasis. J Eur Acad Dermatol Venereol. 2019;33:1984–92.

    Article  CAS  Google Scholar 

  15. Lamer A, Laurent G, Pelayo S, et al. Exploring patient path through Sankey diagram: a proof of concept. Stud Health Technol Inform. 2020;270:218–22.

    PubMed  Google Scholar 

  16. Roux J. Parcours de soins des patients atteints de sclérose en plaques à partir des données médico-administratives en France. 2018. https://tel.archives-ouvertes.fr/tel-02379451.

  17. Wan J, Shin DB, Gelfand JM. Treatment utilization and drug survival of systemic medications among commercially insured children with psoriasis. Pediatr Dermatol. 2021;38:1169–77.

    Article  Google Scholar 

  18. Di Lernia V, Bianchi L, Guerriero C, et al. Adalimumab in severe plaque psoriasis of childhood: a multi-center, retrospective real-life study up to 52 weeks observation. Dermatol Ther. 2019;32:e13091.

    Article  Google Scholar 

  19. Di Lernia V, Guarneri C, Stingeni L, et al. Effectiveness of etanercept in children with plaque psoriasis in real practice: a one-year multicenter retrospective study. J Dermatolog Treat. 2017;18:1–3.

    Google Scholar 

  20. Phan C, Beauchet A, Burztejn AC, et al. Evaluation of children with psoriasis from the BiPe cohort: are patients using biotherapies in real life eligible for phase III clinical studies? Paediatr Drugs. 2019;21:169–75.

    Article  Google Scholar 

  21. Paller AS, Siegfried EC, Pariser DM, et al. Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis. J Am Acad Dermatol. 2016;74:280–7.

    Article  CAS  Google Scholar 

  22. Richard MA; Groupe de recherche sur le psoriasis de la Société Française de Dermatologie. Psoriasis: évaluation initiale et bilan thérapeutique pratique. Ann Dermatol Venereol. 2019;146:440–9.

  23. Mahé E, Reguiai Z, Barthelemy H, et al. Evaluation of risk factors for body weight increment in psoriatic patients on infliximab: a multicentre, cross-sectional study. J Eur Acad Dermatol Venereol. 2014;28:151–9.

    Article  Google Scholar 

  24. Wu MY, Yu CL, Yang SJ, Chi CC. Change in body weight and body mass index in psoriasis patients receiving biologics: a systematic review and network meta-analysis. J Am Acad Dermatol. 2020;82:101–9.

    Article  CAS  Google Scholar 

  25. Mazhar F, Battini V, Pozzi M, et al. Changes in anthropometric parameters after anti-TNFα therapy in inflammatory bowel disease: a systematic review and meta-analysis. BioDrugs. 2020;34:649–68.

    Article  CAS  Google Scholar 

  26. Phan C, Beauchet A, Reguiai Z, et al. Switching biologics in children with psoriasis: results from the BiPe cohort. Pediatr Dermatol. 2022;39:35–41.

    Article  Google Scholar 

  27. Bonifati C, Morrone A, Cristaudo A, Graceffa D. Effectiveness of anti-interleukin 23 biologic drugs in psoriasis patients who failed anti-interleukin 17 regimens. A real-life experience. Dermatol Ther. 2021;34:e14584.

    Article  CAS  Google Scholar 

  28. Sherman S, Solomon Cohen E, Amitay-Laish I, et al. IL-17A inhibitor switching—efficacy of ixekizumab following secukinumab failure. A single-center experience. Acta Derm Venereol. 2019;99:769–73.

    Article  CAS  Google Scholar 

  29. Chiricozzi A, Conti A, Burlando M, et al. Switching from secukinumab to ustekinumab in psoriasis patients: results from a multicenter experience. Dermatol Basel Switz. 2019;235:213–8.

    Article  CAS  Google Scholar 

  30. Damiani G, Conic RRZ, de Vita V, et al. When IL-17 inhibitors fail: Real-life evidence to switch from secukinumab to adalimumab or ustekinumab. Dermatol Ther. 2019;32:e12793.

    Article  Google Scholar 

  31. Tai YC, Tsai TF. Switching biologics in psoriasis—practical guidance and evidence to support. Expert Rev Clin Pharmacol. 2020;13:493–503.

    Article  Google Scholar 

  32. Badaoui A, Tounian P, Mahé E. Psoriasis and metabolic and cardiovascular comorbidities in children: a systematic review. Arch Pediatr. 2019;26:86–94.

    Article  CAS  Google Scholar 

  33. Phan K, Lee G, Fischer G. Pediatric psoriasis and association with cardiovascular and metabolic comorbidities: systematic review and meta-analysis. Pediatr Dermatol. 2020;37:661–9.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dermatology Department, Hôpital Victor Dupouy, Argenteuil, France

    Jinane Zitouni, Céline Phan & Emmanuel Mahé

  2. Public Health Department, Centre Hospitalier Universitaire Ambroise Paré, Boulogne-Billancourt, France

    Alain Beauchet

  3. Sorbonne University, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris, France

    Raphaëlle Curmin

  4. Dermatology unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy

    Vito Di Lernia

  5. Dermatology Department, Hôpitaux de Brabois, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France

    Anne-Claire Bursztejn

  6. Dermatology Department, Centre de référence des maladies rares de la peau et des muqueuses, Hôpital Larrey, Toulouse, France

    Juliette Mazereeuw-Hautier

  7. Immunology and Dermatology Department, Hôpital Bicêtre, CHU de Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, Le Kremlin Bicêtre, France

    Jérémy Gottlieb

  8. Dermatology Department,, Hôpital Saint Vincent de Paul, Université Catholique de Lille, Lille, France

    Audrey Lasek

  9. Dermatology Department, Centre Hospitalier Universitaire de Nantes, Nantes, France

    Hélène Aubert

  10. Dermatology Department, Centre Hospitalier Universitaire Pontchaillou, Rennes, France

    Catherine Droitcourt

  11. Dermatology Department, Hôpital Larrey, Toulouse, France

    Cristina Bulai-Livideanu

  12. Pediatric Dermatology Unit, Department of Medicine DIMED, University of Padova, Padua, Italy

    Anna Belloni Fortina & Francesca Caroppo

  13. Dermatology Department, Hôpital Saint-Joseph, Marseille, France

    Nathalie Quiles-Tsimaratos

  14. Dermatology Department, Hôpital de la Timone, Assistance-publique-Hôpitaux de Marseille, Marseille, France

    Stéphanie Mallet

  15. Dermatology Department, Centre Hospitalier d’Auxerre, Auxerre, France

    Hugues Barthélémy

  16. Dermatology Department, Centre Hospitalier Universitaire Saint-Jacques, Besançon, France

    Eve Puzenat

  17. Dermatology Department, Centre Hospitalier Universitaire de Dijon, Dijon, France

    Danielle Bouilly-Auvray

  18. Dermatology, Department of Experimental, Diagnostic, and Specialty Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    Iria Neri

Authors
  1. Jinane Zitouni
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  2. Alain Beauchet
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  3. Raphaëlle Curmin
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  4. Vito Di Lernia
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  5. Anne-Claire Bursztejn
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  6. Juliette Mazereeuw-Hautier
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  7. Jérémy Gottlieb
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  8. Audrey Lasek
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  9. Hélène Aubert
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  10. Catherine Droitcourt
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  11. Cristina Bulai-Livideanu
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  12. Anna Belloni Fortina
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  13. Francesca Caroppo
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  14. Nathalie Quiles-Tsimaratos
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  15. Stéphanie Mallet
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  16. Hugues Barthélémy
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  17. Eve Puzenat
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  18. Danielle Bouilly-Auvray
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  19. Iria Neri
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  20. Céline Phan
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  21. Emmanuel Mahé
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Consortia

Groupe de Recherche sur le Psoriasis (GrPso) of the Société Française de Dermatologie, Groupe de Recherche de la Société Française de Dermatologie Pédiatrique (GR SFDP), and Società Italiana di Dermatologia Pediatrica (S.I.Der.P.)

Corresponding author

Correspondence to Emmanuel Mahé.

Ethics declarations

Ethics Declarations

In France and Italy, an ethics declaration is not necessary for retrospective data. We only required “non-opposition for participating to the study”.

Funding

No sources of funding were used to conduct this study or prepare this manuscript.

Conflicts of interest

V. Di Lernia: AbbVie and Novartis. J. Gottlieb: AbbVie, Celgene, Lilly, Novartis, Janssen Cilag, and UCB. N. Quiles-Tsimaratos: AbbVie, Celgene, Janssen Cilag, Leo Pharma, Lilly, Novartis, Pfizer, and UCB. H. Barthelemy: AbbVie, JanssenCilag, Leo Pharma, and Pfizer. I. Neri: Janssen Cilag, Sanofi, and Lilly. E. Mahé: AbbVie, Amgen, Celgene, Janssen Cilag, Leo Pharma, Lilly, and Novartis.

Ethics approval

We required the “non-opposition for participating to the study”.

Consent to participate

We required the “non-opposition for participating to the study”.

Consent for publication

We required the “non-opposition for participating to the study”.

Availability of data and materials

Data available on request to E. Mahé.

Code availability

Not applicable.

Author contributions

All authors: interpretation of data; revised critically the work, approved the version to be published. Vito Di Lernia, Anne-Claire Bursztejn, Juliette Mazereeuw-Hautier, Jérémy Gottlieb, Audrey Lasek, Hélène Aubert, Catherine Droitcourt, Cristina Bulai-Livideanu, Anna Belloni Fortina, Francesca Caroppo, Nathalie Quiles-Tsimaratos, Stéphanie Mallet, Hugues Barthélémy, Eve Puzenat, Danielle Bouilly-Auvray, Iria Neri,and Céline Phan: acquisition of data. Alain Beauchet and Raphaëlle Curmin: statistical analysis. J Zitouni and Emmanuel Mahé: conception, design, acquisition, part of analysis, creation of network, wrote the article.

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Zitouni, J., Beauchet, A., Curmin, R. et al. Effectiveness and Safety of Adalimumab, Etanercept and Ustekinumab for Severe Psoriasis in Children Under 12 Years of Age: A French-Italian Daily Practice Cohort (BiPe Jr). Pediatr Drugs 24, 281–292 (2022). https://doi.org/10.1007/s40272-022-00501-6

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