Efficacy and safety of thalidomide for recurrent aphthous stomatitis: a systematic review and meta-analysis of randomized controlled trials.
Meta-analysis
Recurrent aphthous stomatitis
Stomatitis, Aphthous
Systematic review
Thalidomide
Journal
BMC oral health
ISSN: 1472-6831
Titre abrégé: BMC Oral Health
Pays: England
ID NLM: 101088684
Informations de publication
Date de publication:
28 Sep 2024
28 Sep 2024
Historique:
received:
05
03
2024
accepted:
16
09
2024
medline:
29
9
2024
pubmed:
29
9
2024
entrez:
28
9
2024
Statut:
epublish
Résumé
Recurrent aphthous stomatitis (RAS) is considered as the most common oral mucosal lesion affecting up to 25% of people worldwide. Thalidomide has been reported for the treatment of RAS, but the evidence has not been systematically evaluated. We first systematically reviewed the efficacy and safety of thalidomide for the treatment of RAS. We searched The Cochrane Library, PubMed, Scopus, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wanfang Data, and VIP information from inception to December 2023. Randomized controlled trials (RCTs) comparing thalidomide with control for RAS were included in the analysis. The primary outcome were complete response and overall response, and the secondary outcome were recurrence interval (RI), ulcer number and size, healing time, visual analogue scale (VAS), immunological data, and adverse events. Meta-analysis was conducted using the Review Manager 5.4 software. Twenty-one trials involving 1668 patients were included in this review. The results of our meta-analysis showed that thalidomide significantly improved the complete response rate and overall response rate, prolonged the recurrence interval, accelerated the healing process, reduced the number and size of ulcers, and lowered TNF-α levels in the treatment of RAS. However, thalidomide significantly increases adverse events. Thalidomide has a significant benefit in the treatment of RAS. However, considering the potential side effects of thalidomide, it may be an optimal treatment option for major RAS patients or cases that do not respond to topical agents. PROSPERO registration number: CRD42024495038.
Sections du résumé
BACKGROUND
BACKGROUND
Recurrent aphthous stomatitis (RAS) is considered as the most common oral mucosal lesion affecting up to 25% of people worldwide. Thalidomide has been reported for the treatment of RAS, but the evidence has not been systematically evaluated. We first systematically reviewed the efficacy and safety of thalidomide for the treatment of RAS.
METHODS
METHODS
We searched The Cochrane Library, PubMed, Scopus, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wanfang Data, and VIP information from inception to December 2023. Randomized controlled trials (RCTs) comparing thalidomide with control for RAS were included in the analysis. The primary outcome were complete response and overall response, and the secondary outcome were recurrence interval (RI), ulcer number and size, healing time, visual analogue scale (VAS), immunological data, and adverse events. Meta-analysis was conducted using the Review Manager 5.4 software.
RESULTS
RESULTS
Twenty-one trials involving 1668 patients were included in this review. The results of our meta-analysis showed that thalidomide significantly improved the complete response rate and overall response rate, prolonged the recurrence interval, accelerated the healing process, reduced the number and size of ulcers, and lowered TNF-α levels in the treatment of RAS. However, thalidomide significantly increases adverse events.
RESULTS
RESULTS
Thalidomide has a significant benefit in the treatment of RAS. However, considering the potential side effects of thalidomide, it may be an optimal treatment option for major RAS patients or cases that do not respond to topical agents.
TRIAL REGISTRATION
BACKGROUND
PROSPERO registration number: CRD42024495038.
Identifiants
pubmed: 39342210
doi: 10.1186/s12903-024-04923-1
pii: 10.1186/s12903-024-04923-1
doi:
Substances chimiques
Thalidomide
4Z8R6ORS6L
Types de publication
Journal Article
Systematic Review
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
1149Informations de copyright
© 2024. The Author(s).
Références
Jonathan AS, Arbor DMD, Mich A. Recurrent aphthous stomatitis: an update. Oral Surg Oral Med Oral Pathol Oral Radiol. 1996;81(2):141–7.
doi: 10.1016/S1079-2104(96)80403-3
Barrons RW. Treatment strategies for recurrent oral aphthous ulcers. Am J Health-Syst Pharm. 2001;58(1):41–50.
pubmed: 11194135
doi: 10.1093/ajhp/58.1.41
Altenburg A, El-Haj N, Micheli C, Puttkammer M, Abdel-Naser MB, Zouboulis CC. The treatment of chronic recurrent oral aphthous ulcers. Dtsch Arztebl Int. 2014;111(40):665–73.
pubmed: 25346356
pmcid: 4215084
Wang ZH, Cao HB, Xiong JQ, Lu YL, Deng YX, Nan H, et al. Recent advances in the aetiology of recurrent aphthous stomatitis (RAS). Postgrad Med J. 2022;98(1155):57–66.
pubmed: 33574180
doi: 10.1136/postgradmedj-2020-139421
Slebioda Z, Szponar E, Kowalska A. Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review. Arch Immunol Ther Exp. 2014;62:205–15.
doi: 10.1007/s00005-013-0261-y
Manfredini M, Guida S, Giovani M, Lippolis N, Spinas E, Farnetani F, et al. Recurrent aphthous stomatitis: treatment and management. Dermatol Pract Concept. 2021;11(4):e2021099.
pubmed: 34631263
pmcid: 8480451
doi: 10.5826/dpc.1104a99
Tarakji B, Gazal G, Al-Maweri SA, Azzeghaiby SN, Alaizari N. Guideline for the diagnosis and treatment of recurrent Aphthous Stomatitis for Dental Practitioners. J Int Oral Health. 2015;7(5):74–80.
pubmed: 26028911
pmcid: 4441245
Shi LJ, Zhou ZT. Diagnosis and management of recurrent aphthous ulcer. Chin J Stomatol. 2022;57(3):314–8.
Vargesson N. Thalidomide-induced teratogenesis: history and mechanisms. Birth Defects Res C Embryo Today. 2015;105(2):140–56.
pubmed: 26043938
pmcid: 4737249
doi: 10.1002/bdrc.21096
Wang DD, Chen HF, Wang SY, Zou YH, Li J, Pan JP, et al. Thalidomide treatment in cutaneous lesions of systemic lupus erythematosus: a multicenter study in China. Clin Rheumatol. 2016;35(6):1521–7.
pubmed: 27097914
doi: 10.1007/s10067-016-3256-3
Lu YF, Wei ZB, Yang GH, Lai YR, Liu RR. Investigating the efficacy and safety of Thalidomide for treating patients with β-Thalassemia: a Meta-analysis. Front Pharmacol. 2022;12:814302.
pubmed: 35087410
pmcid: 8786914
doi: 10.3389/fphar.2021.814302
Huang F, Gu JR, Zhao W, Zhu J, Zhang JL, Yu DT. One-year open-label trial of thalidomide in ankylosing spondylitis. Arthritis Rheum. 2002;47(3):249–54.
pubmed: 12115153
doi: 10.1002/art.10396
Aguiar PM, de Mendonça Lima T, Colleoni GWB, Storpirtis S. Efficacy and safety of bortezomib, thalidomide, and lenalidomide in multiple myeloma: an overview of systematic reviews with meta-analyses. Crit Rev Oncol Hematol. 2017;113:195–212.
pubmed: 28427509
doi: 10.1016/j.critrevonc.2017.03.014
Paterson DL, Georghiou PR, Allworth AM, Kemp RJ. Thalidomide as treatment of refractory aphthous ulceration related to human immunodeficiency virus infection. Clin Infect Dis. 1995;20(2):250–4.
pubmed: 7742424
doi: 10.1093/clinids/20.2.250
Harte MC, Saunsbury TA, Hodgson TA. Thalidomide use in the management of oromucosal disease: a 10-year review of safety and efficacy in 12 patients. Oral Surg Oral Med Oral Pathol Oral Radiol. 2020;130(4):398–401.
pubmed: 32622799
doi: 10.1016/j.oooo.2020.06.009
Hamuryudan V, Mat C, Saip S, Ozyazgan Y, Siva A, Yurdakul S, et al. Thalidomide in the treatment of the mucocutaneous lesions of the Behçet syndrome: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998;128(6):443–50.
pubmed: 9499327
doi: 10.7326/0003-4819-128-6-199803150-00004
Xue HX, Fu WY, Cui HD, Yang LL, Zhang N, Zhao LJ. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis. Neural Regen Res. 2015;10(5):814–8.
pubmed: 26109960
pmcid: 4468777
doi: 10.4103/1673-5374.156988
Moore TJ, Bennett CL. Underreporting of hemorrhagic and thrombotic complications of pharmaceuticals to the U.S. Food and Drug Administration: empirical findings for warfarin, clopidogrel, ticlopidine, and thalidomide from the Southern Network on adverse reactions (SONAR). Semin Thromb Hemost. 2012;38(8):905–7.
pubmed: 23086541
pmcid: 3947536
doi: 10.1055/s-0032-1328890
Hello M, Barbarot S, Bastuji-Garin S, Revuz J, Chosidow O. Use of thalidomide for severe recurrent aphthous stomatitis: a multicenter cohort analysis. Med (Baltim). 2010;89(3):176–82.
doi: 10.1097/MD.0b013e3181dfca14
Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
pubmed: 22008217
pmcid: 3196245
doi: 10.1136/bmj.d5928
Higgins J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane Handbook for Systematic Reviews of Interventions. 2nd Edition. Chichester (UK): John Wiley & Sons; 2019.
Chen H, He J, Zhou SL, Zhang EP. Comparison of effect on major recurrent aphtha with different methods of treatment. J Dent Prevent Treat. 2014;22(1):18–21.
Deng YW, Wei W, Wang YF, Pan L, Du GH, Yao H, et al. A randomized controlled clinical trial on dose optimization of thalidomide in maintenance treatment for recurrent aphthous stomatitis. J Oral Pathol Med. 2022;51(1):106–12.
pubmed: 34773292
doi: 10.1111/jop.13259
Gao Q, Chen HZ, Li HB, Jia ZY. The clinical effects of thalidomide in the treatment of Major Aphthous Ulcer. J Mod Stomatol. 2007;21(3):326.
Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. N Engl J Med. 1997;336:1487–93.
pubmed: 9154767
doi: 10.1056/NEJM199705223362103
Revuz J, Guillaume J-C, Janier M, Hans P, Marchand C, Souteyrand P. Crossover study of Thalidomide vs placebo in severe recurrent aphthous stomatitis. Arch Dermatol. 1990;126:923–7.
pubmed: 2193629
doi: 10.1001/archderm.1990.01670310085012
Lin YH. Clinical study of thalidomide in the treatment of recurrent oral ulcer. J Med Aesthet Cosmetol. 2020;29(16):83.
Mimura MAM, Hirota SK, Sugaya NN, Sanches JA Jr., Migliari DA. Systemic treatment in severe cases of recurrent aphthous stomatitis: an open trial. Clinics. 2009;64(3):193–8.
pubmed: 19330244
pmcid: 2666466
doi: 10.1590/S1807-59322009000300008
Peng Y. Montmorillonite dispersed and Sally amine curative effect analysis for the treatment of recurrent oral ulcer. J Gen Stomatol. 2015;2(4):88–90.
Ramirez-Amador VA, Lilly EP, Sergio PDL, Gustavo RT, Martha GG, Samuel PDL, et al. Thalidomide as therapy for human immunodeficiency virus-related oral ulcers: a double-blind placebo-controlled clinical trial. Clin Infect Dis. 1999;28:892–4.
pubmed: 10825055
doi: 10.1086/515222
Tian FQ, Tang MQ, Li JH, Huang YC, Li HQ, Zhong QZ, et al. Clinical study of thalidomide treating oral ulcers secondary to acute leukemia. J Clin Hematol. 2016;29(5):404–5.
Wang PH, Zhong SS, Su RB. The clinical efficacy and safety of thalidomide combined with vitamin B1 and vitamin AD in the treatment of recurrent aphthous ulcer. Chin J Clin Ration Drug Use. 2022;15(30):152–4.
Xu HX, Qiu P. The clinical effects of thalidomide combined with total glucosides of Paeony Capsules in the treatment of RAU. Clin Res Pract. 2016;1(02):34.
Xu HY, Jiao HM, Guo YL, Li F. The clinical effects of low dose thalidomide combined with multivitamin and minerals tablet for treating recurrent aphthous ulcer. Shaanxi Med J. 2018;47(2):238–40.
Xu JC, Chen ZL. Clinical observation of thalidomide combined with total glucosides of Paeony Capsules in the treatment of recurrent aphthous ulcer. Strait Pharm J. 2017;29(06):108–10.
Xu Q. Clinical observation of thalidomide in the treatment of recurrent aphthous ulcer. Strait Pharm J. 2019;31(12):127–9.
Xu Q, Zhou L. Effect of Thalidomide combined with cimetidine on the treatment of recurrent oral Ulcer. Shenzhen Vintegr Tradit Chin West Med. 2021;31(20):153–5.
Zeng QX, Shi XK, Yang J, Yang M, Zhao W, Zhao XY, et al. The efficacy and safety of thalidomide on the recurrence interval of continuous recurrent aphthous ulceration: a randomized controlled clinical trial. J Oral Pathol Med. 2019;00:1–8.
Zhang J, Ma M, Zhu LH. Short-term effects of thalidomide in the treatment of recurrent aphthous ulcer. J Ningxia Med Univ. 2010;32(09):997–9.
Zong JJ, Lin L, Su S. Effect of thalidomide in the treatment of intractable recurrent aphthous ulcer. J Nanchang Univ(Med Sci). 2014;54(10):71–2.
Zhou H, Huang FY. The clinical efficacy of thalidomide for recurrent oral aphthous ulcers. Med J West China. 2011;23(8):1534–7.
Zhong ZQ, Cai ZX. Clinical study of thalidomide combined with prednisone in the treatment of major aphthous ulcer. Stomatol. 2011;31(06):376–8.
Edgar NR, Saleh D, Miller RA. Recurrent aphthous stomatitis: a review. J Clin Aesthet Dermatol. 2017;10(3):26–36.
pubmed: 28360966
pmcid: 5367879
Dhopte A, Naidu G, Singh-Makkad R, Nagi R, Bagde H, Jain S. Psychometric analysis of stress, anxiety and depression in patients with recurrent aphthous Stomatitis-A cross-sectional survey based study. J Clin Exp Dent. 2018;10(11):e1109–14.
pubmed: 30607229
pmcid: 6311397
Saikaly SK, Saikaly TS, Saikaly LE. Recurrent aphthous ulceration: a review of potential causes and novel treatments. J Dermatolog Treat. 2018;29(6):542–52.
pubmed: 29278022
doi: 10.1080/09546634.2017.1422079
Lewkowicz N, Lewkowicz P, Banasik M, Kurnatowska A, Tchórzewski H. Predominance of type cytokines and decreased number of CD4(+)CD25(+ high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations. Immunol Lett. 2005;99(1):57–62.
pubmed: 15894112
doi: 10.1016/j.imlet.2005.01.002
Borra RC, Andrade PM, Silva ID, Morgun A, Weckx LL, Smirnova AS, et al. The Th1/Th2 immune-type response of the recurrent aphthous ulceration analyzed by cDNA microarray. J Oral Pathol Med. 2004;33(3):140–6.
pubmed: 15128055
doi: 10.1111/j.0904-2512.2004.00089.x
Lewkowicz N, Kur B, Kurnatowska A, Tchorzewski H, Lewkowicz P. Expression of Th1/Th2/Th3/Th17-Related genes in recurrent aphthous ulcers. Arch Immunol Ther Exp. 2011;59(5):399–406.
doi: 10.1007/s00005-011-0134-1
Chaudhuri K, Nair KK, Ashok L. Salivary levels of TNF-α in patients with recurrent aphthous stomatitis: a cross-sectional study. J Dent Res Dent Clin Dent Prospects. 2018;12(1):45–8.
pubmed: 29732020
pmcid: 5928473
doi: 10.15171/joddd.2018.007
Surboyo MDC, Boedi RM, Hariyani N, Santosh ABR, Manuaba IBPP, Cecilia PH, et al. The expression of TNF-α in recurrent aphthous stomatitis: a systematic review and meta-analysis. Cytokine. 2022 sep;157:155946.
Lewkowicza N, Lewkowiczb P, Banasikb M, Kurnatowska A, Tchorzewski H. Predominance of type 1 cytokines and decreased number of CD4 + CD25 + high T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations. Immunol Lett. 2005;99(1):57–62.
doi: 10.1016/j.imlet.2005.01.002
Kim YS, Kim JS, Jung HC, Song IS. The effects of thalidomide on NF-kB activity and TNF-α production stimulated with lipopolysaccharide in a human colonic epithelial cell line. Mol Cells. 2004;17(2):210–6.
pubmed: 15179032
doi: 10.1016/S1016-8478(23)13028-7
Noman AS, Koide N, Hassan F, I-E-Khuda I, Dagvadorj J, Tumurkhuu G, et al. Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-α production via down-regulation of MyD88 expression. Innate Immun. 2009;15(1):33–41.
pubmed: 19201823
doi: 10.1177/1753425908099317
Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G. Thalidomide exerts its inhibitory action on tumor necrosis factor α by enhancing mRNA degradation. J Exp Med. 1993 jun;177(6):1675–80.
Brocklehurst P, Tickle M, Glenny AM, Lewis MA, Pemberton MN, Taylor J, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev. 2012 Sep;12(9):CD005411.
Lau CB, Smith GP. Recurrent aphthous stomatitis: a comprehensive review and recommendations on therapeutic options. Dermatol Ther. 2022;35(6):e15500.
pubmed: 35395126
doi: 10.1111/dth.15500
Wei W, Deng YW, Wang YF, Yao H, Du GH, Tang GY. Dynamic salivary cytokine profile of recurrent aphthous stomatitis patients in thalidomide maintenance treatment. Clin Oral Investig. 2024;28(2):140.
pubmed: 38334890
doi: 10.1007/s00784-024-05531-7