SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Effectiveness of "Tumor Necrosis Factor inhibitors" in Monogenic Hereditary Recurrent Fevers in Children and Adolescents: A Systematic Review
Provisionally accepted
Rim Dhahri1
Soumaya Boussaid2*
Lobna Ben Ammar1
safa rahmouni3
Insaf Fenniche1khaoula zouaoui3hiba ben ayed1sonia rekik3khalil amri1hela sahli3imen gharsallah1- 1Hopital Militaire Principal d'Instruction de Tunis, Tunis, Tunisia
- 2Hôpital La Rabta, Tunis, Tunisia
- 3Hopital La Rabta, Tunis, Tunisia
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Abstract : Introduction: This systematic review aims to evaluate the clinical effectiveness of tumor necrosis factor (TNF) inhibitors in treating monogenic hereditary recurrent fevers (HRFs) in children and adolescents. Methods: We conducted a comprehensive literature search across MEDLINE, EMBASE, and Scopus up to May 2024, including case reports, case series, and observational studies involving pediatric patients with HRFs treated with TNF inhibitors. Articles were screened and selected based on PRISMA guidelines. Results: Eleven pediatric cases were identified from ten studies, including patients with FMF (n=2), MKD/MKD (n=5), TRAPS (n=2), and CAPS (n=2). Etanercept was the most frequently used TNF inhibitor (10/11 cases), and infliximab was used in one FMF case. Follow-up duration ranged from 3 months to 4 years. Clinical responses varied: full remission in TRAPS cases; partial improvement in some MKD and CAPS cases; and no significant effect in several FMF and MKD/MKD patients. Etanercept showed the best outcomes in TRAPS, while responses in CAPS and MKD/MKD were inconsistent. Conclusion: TNFi may offer a therapeutic option for selected pediatric HRF cases, particularly colchicine-resistant FMF with articular symptoms or where IL-1 blockers are unavailable. However, their efficacy appears limited and variable across HRF subtypes. Larger studies are needed to better define the role of TNF inhibitors in pediatric HRFs
Keywords: Monogenic Hereditary Recurrent Fevers, TNF inhibitors, pediatric rheumatology, Tumor necrosis factor inhibitors, Systematic review
Received: 21 Sep 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Dhahri, Boussaid, Ben Ammar, rahmouni, Fenniche, zouaoui, ben ayed, rekik, amri, sahli and gharsallah. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Soumaya Boussaid, soumayaboussaid@hotmail.com
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