Proposal for a new therapeutic high dosage of Pidotimod in children with periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: a randomized controlled study
Tóm tắt
Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome. 22 children with PFAPA syndrome were randomly allocated to treatment with pidotimod (with 2 vials of 400 mg daily) in combination with betamethasone 0.5–1 mg on need, based on parents/caregivers’ decision (group A) or betamethasone 0.5-1 mg on need, based on parents/caregivers’ decision (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, pharyngitis, or aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment. Patients receiving Pidotimod and use betametasone showed a significant decrease in frequency of fevers (p = 0.002); number of episodes of pharyngitis (p = 0.049); aphthous stomatitis (p = 0.036) as well as the betamethasone use on need (p = 0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups. We firstly showed that high dosage of Pidotimod could be an effective and safe to reduce the PFAPA attacks in children.
Tài liệu tham khảo
Marshall GS, Edwards KM, Butler J, Lawton AR. Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr. 1987;110(1):43–6.
Reimann HA. Periodic disease: a probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia. JAMA. 1948;I36:239–44.
Førsvoll J, Kristoffersen EK, Øymar K. Incidence, clinical characteristics and outcome in Norwegian children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome; a population-based study. Acta Paediatr. 2012;102(2):187–92.
Long S. Syndrome of periodic fever, Aphthous stomatitis, pharyngitis, and adenitis (PFAPA) what it isn’t. What is it? J Pediatr. 1999;135(1):1–5.
Adrovic A, Yıldız M, Kanber M, Ulkersoy I, Gucuyener N, Koker O, et al. Performance of recently proposed periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome criteria in a region endemic for familial Mediterranean fever. Rheumatol Int. 2020;40(1):91–6.
Vanoni F, Caorsi R, Aeby S, Barron KS, Brogan P, De Benedetti F, et al. Towards a new set of classification criteria for PFAPA`w syndrome. Pediatr Rheumatol Online J. 2018;16:60.
Vanoni F, Federici S, Antón J, Barron KS, Brogan P, De Benedetti F, et al. An international delphi survey for the definition of the variables for the development of new classification criteria for periodic fever aphtous stomatitis pharingitis cervical adenitis (PFAPA). Pediatr Rheumatol Online J. 2018;16(1):27.
Vanoni F, Theodoropoulou K, Hofer M. PFAPA syndrome: a review on treatment and outcome. Pediatr Rheumatol. 2016;14:38.
Førsvoll J, Øymar K. The role of tonsillectomy in the periodic fever, Aphthous stomatitis, pharyngitis and cervical adenitis syndrome; a literature review. BMC Ear Nose Throat Disord. 2018;18:3.
Stagi S, Bertini F, Rigante D, Falcini F. Vitamin D levels and effects of vitamin D replacement in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Int J Pediatr Otorhinolaryngol. 2014;78(6):964–8.
Niu H, Wang R, Jia YT, Cai Y. Pidotimod, an immunostimulant in pediatric recurrent respiratory tract infections: a meta-analysis of randomized controlled trials. Int Immunopharmacol. 2019;67:35–45.
Valentini D, Di Camillo C, Mirante N, et al. Effects of Pidotimod on recurrent respiratory infections in children with Down syndrome: a retrospective Italian study. Ital J Pediatr. 2020;46:31.
Buongiorno A, Pierossi N. Effectiveness of pidotimod in combination with bacterial lysates in the treatment of the PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome. Minerva Pediatr. 2015;67(3):219–26.
Suresh K. An overview of randomization techniques: an unbiased assessment of outcome in clinical research. J Hum Reprod Sci. 2011;4(1):8–11.
Agresti A, Min Y. On Sample Size Guidelines for Teaching Inference about the Binomial Parameter in Introductory Statistics. Department of Statistics University of Florida. Gainesville, Florida; 2002. p. 32611–8545.
Harel L, Hashkes PJ, Lapidus S, et al. The First International Conference on Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis Syndrome. J Pediatr. 2018;193:265–274.e3.
Gaggiano C, Rigante D, Sota J, Grosso S, Cantarini L. Treatment options for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome in children and adults: a narrative review. Clin Rheumatol. 2019;38(1):11–7.
Caccuri F, Bugatti A, Corbellini S, Roversi S, Zani A, Mazzuca P, et al. The synthetic dipeptide Pidotimod shows a chemokine-like activity through CXC chemokine receptor 3 (CXCR3). Int J Mol Sci. 2019;20(21):5287.