Efficacy and safety of thalidomide in children with monogenic autoinflammatory diseases: a single-center, real-world-evidence study.
Efficacy
Monogenic autoinflammatory disease
Safety
Thalidomide
Journal
Pediatric rheumatology online journal
ISSN: 1546-0096
Titre abrégé: Pediatr Rheumatol Online J
Pays: England
ID NLM: 101248897
Informations de publication
Date de publication:
17 Oct 2023
17 Oct 2023
Historique:
received:
16
03
2023
accepted:
23
08
2023
medline:
23
10
2023
pubmed:
18
10
2023
entrez:
17
10
2023
Statut:
epublish
Résumé
Monogenic autoinflammatory diseases (AIDs) are rare inflammatory diseases caused by genetic variants. The pathogenesis is complex and treatment options are limited. This study aimed to describe the safety and efficacy of thalidomide in the treatment of monogenic AIDs. This was a single-center, single-arm, real-world study. From September 2016 to August 2021, patients with monogenic AIDs who met the inclusion and exclusion criteria were given thalidomide for 12 months. There was a 3-month run-in period before dosing. The efficacy and adverse events were evaluated and recorded every 3 months. After 3 and 12 months of thalidomide treatment, clinical manifestations, disease activity score, inflammatory markers, and background medication adjustments were compared with baseline for efficacy analyses. A total of 16 patients entered this study, including 3 with Aicardi-Goutières syndrome (AGS), 4 Blau syndrome, 2 chronic infantile neurologic cutaneous articular syndrome (CINCA), 2 A20 haploinsufficiency (HA20), 1 adenosine deaminase 2 deficiency(DADA2), 1 familial Mediterranean fever (FMF),1 tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), 1 PLCγ2-associated antibody deficiency and immune dysregulation (PLAID), and 1 stimulator of interferon genes-associated vasculopathy with onset in infancy(SAVI). The efficacy rate in the 16 patients after 3-month and 12-month thalidomide treatment in patients was 56.3%. Twelve patients completed the study, the fever improved in all of them, rash improved in 7 patients, and 5 patients stopped using glucocorticoids or other immunosuppressive agents. C-reactive protein was normal in 8 patients and erythrocyte sedimentation rate was normal in 11 patients. Anorexia and nausea occurred in 2 cases, with no other reported drug-related adverse reactions. The largest cohort of monogenic AIDs with the treatment of thalidomide demonstrated that thalidomide can help reduce disease activity and inflammation, reduce the dosage of glucocorticoids, and improve clinical outcomes. Thalidomide is relatively safe in monogenic AIDs.
Sections du résumé
BACKGROUND
BACKGROUND
Monogenic autoinflammatory diseases (AIDs) are rare inflammatory diseases caused by genetic variants. The pathogenesis is complex and treatment options are limited. This study aimed to describe the safety and efficacy of thalidomide in the treatment of monogenic AIDs.
METHODS
METHODS
This was a single-center, single-arm, real-world study. From September 2016 to August 2021, patients with monogenic AIDs who met the inclusion and exclusion criteria were given thalidomide for 12 months. There was a 3-month run-in period before dosing. The efficacy and adverse events were evaluated and recorded every 3 months. After 3 and 12 months of thalidomide treatment, clinical manifestations, disease activity score, inflammatory markers, and background medication adjustments were compared with baseline for efficacy analyses.
RESULTS
RESULTS
A total of 16 patients entered this study, including 3 with Aicardi-Goutières syndrome (AGS), 4 Blau syndrome, 2 chronic infantile neurologic cutaneous articular syndrome (CINCA), 2 A20 haploinsufficiency (HA20), 1 adenosine deaminase 2 deficiency(DADA2), 1 familial Mediterranean fever (FMF),1 tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), 1 PLCγ2-associated antibody deficiency and immune dysregulation (PLAID), and 1 stimulator of interferon genes-associated vasculopathy with onset in infancy(SAVI). The efficacy rate in the 16 patients after 3-month and 12-month thalidomide treatment in patients was 56.3%. Twelve patients completed the study, the fever improved in all of them, rash improved in 7 patients, and 5 patients stopped using glucocorticoids or other immunosuppressive agents. C-reactive protein was normal in 8 patients and erythrocyte sedimentation rate was normal in 11 patients. Anorexia and nausea occurred in 2 cases, with no other reported drug-related adverse reactions.
CONCLUSION
CONCLUSIONS
The largest cohort of monogenic AIDs with the treatment of thalidomide demonstrated that thalidomide can help reduce disease activity and inflammation, reduce the dosage of glucocorticoids, and improve clinical outcomes. Thalidomide is relatively safe in monogenic AIDs.
Identifiants
pubmed: 37848905
doi: 10.1186/s12969-023-00881-0
pii: 10.1186/s12969-023-00881-0
pmc: PMC10583446
doi:
Substances chimiques
Thalidomide
4Z8R6ORS6L
Adenosine Deaminase
EC 3.5.4.4
Intercellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
124Subventions
Organisme : National Key Research and Development Program of China
ID : 2021YFC2702001
Organisme : Beijing Natural Science Foundation
ID : L202050
Organisme : National High Level Hospital Clinical Research Funding
ID : 2022-PUMCH-B-079
Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
Références
J Oncol Pharm Pract. 2021 Apr;27(3):673-678
pubmed: 33249990
Front Med (Lausanne). 2022 Mar 24;9:856786
pubmed: 35402426
Arthritis Rheum. 2010 Jan;62(1):250-7
pubmed: 20039400
J Allergy Clin Immunol. 2020 Nov;146(5):925-937
pubmed: 33160483
Rheumatol Int. 2022 Jan;42(1):81-86
pubmed: 34550430
Arch Rheumatol. 2021 Jan 14;36(2):219-226
pubmed: 34527926
Int J Mol Sci. 2022 Feb 05;23(3):
pubmed: 35163749
Scand J Rheumatol. 2005 May-Jun;34(3):246-9
pubmed: 16134734
Annu Rev Pathol. 2022 Jan 24;17:227-249
pubmed: 34699263
Ann Rheum Dis. 2017 Oct;76(10):1648-1656
pubmed: 28522451
Pediatr Rheumatol Online J. 2021 May 24;19(1):75
pubmed: 34030699
Front Immunol. 2021 May 19;12:667430
pubmed: 34093563
Cells. 2022 Jul 18;11(14):
pubmed: 35883675
Front Immunol. 2022 Mar 28;13:825367
pubmed: 35418997
JAMA Dermatol. 2015 Jun;151(6):627-34
pubmed: 25760457
J Clin Immunol. 2023 May;43(4):780-793
pubmed: 36729249
Lancet. 2004 May 29;363(9423):1802-11
pubmed: 15172781
J Eur Acad Dermatol Venereol. 2020 Feb;34(2):340-348
pubmed: 31541486
Clin Exp Rheumatol. 2002 Jul-Aug;20(4 Suppl 26):S43-4
pubmed: 12371635
Pediatr Rheumatol Online J. 2023 Feb 10;21(1):15
pubmed: 36765385
World J Gastroenterol. 2017 Nov 21;23(43):7727-7734
pubmed: 29209113
Ann Palliat Med. 2022 Jul;11(7):2538-2543
pubmed: 34775778
Clin Rheumatol. 2016 Jun;35(6):1521-7
pubmed: 27097914
Nat Immunol. 2017 Jul 19;18(8):832-842
pubmed: 28722725
Ann Rheum Dis. 2018 Nov;77(11):1558-1565
pubmed: 30100561
Biomedicines. 2021 Dec 07;9(12):
pubmed: 34944673
J Clin Immunol. 2022 Oct;42(7):1473-1507
pubmed: 35748970