Galioto GB (ed): Tonsils: A Clinically Oriented Update. Adv Otorhinolaryngol. Basel, Karger, 1992, vol 47, pp 328-331
Pidotimod in the Prophylaxis of Recurrent Acute Tonsillitis in Childhood P. Careddu, A. Biolchini, S. Alfano, G. Zavattini First Department of Pediatrics, University of Milan, and Medical Department, Poli Industria Chimica SpA, Milan, Italy
Recurrent acute tonsillitis is one of the most frequently met with respiratory infections in childhood. Immunologic immaturity is often the cause of this condition while recurrent infections change the cell-mediated immunity. Hence the need for a drug capable of inhibiting this interactive mechanism and stimulating immunity. Pidotimod is a synthetic oral biological response modifier (BRM) (3-L-pyroglutamoil-L-thiazolidin-4-carboxylic acid) proved capable of improving the lymphocytic blastogenesis index and the activation of neutrophil granulocytes as well as increasing the T helper/T suppressor ratio in longlasting treatment [1-3]. In the light of the above considerations, a clinical assessment of pidotimod effectiveness and tolerability in children affected with recurrent acute tonsillitis was deemed to be useful.
Patients and Methods
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Thirty-eight outpatients (table 1) of both sexes, aged 2-14 years, were admitted to this randomized double-blind trial versus placebo according to the following inclusion criteria: (a) phlogistic episodes of recurrent acute tonsillitis occurred at least once a month during the past year, and (b) absence of severe hepatic, renal, cardiac or hematopoietic disorders. Patients who received immunostimulants in the 2 months preceding the trial were excluded. Patients were treated at random with either two 400-mg pidotimod sachets or two indistinguishable placebo sachets every day for 20 consecutive days. Clinical tests were made at baseline (To), at the end of the treatment (T 20), at the first (T 50) and the second (T 80) visit of the follow-up period to assess the following parameters:
A New BRM and Childhood Tonsillitis
329
Table 1. Characteristics of patients
Patients Male/female ratio Age, years (x±SD) Age range, years Body weight, kg (x ± SD) Diagnosis Tonsillitis Follicular tonsillitis Pharyngeal tonsillitis Tonsillitis during last winter (x ± SD)
Pidotimod
Placebo
19 10/9 5.8±3.22 2-14 21.8± 10.7
19 10/9 7.3±3.22 3-13 25.3± 10.7
10 I
8 4.5 ± 1.43
8 2 9 4.4± 1.3
the trend of basic disease (number, duration and severity of recurrences during the trial and their effect on antibiotic consumption and capability of attending school); the sign and symptom pattern (dysphagia, nasal stuffiness, cough, pharyngeal hyperemia, tonsillar hypertrophy); laboratory tests showing changes in blood composition, hemopoiesis, hepatic and renal function. At the end of the trial both the physician in charge and the patients were requested to rate the effectiveness and tolerability of the treatment.
The patients showing no recurrences during the treatment and followup period were 12 (63.1 %) in the pidotimod group and 5 (26.3%) in the placebo group. The difference between the two groups (36.8 %) is statistically significant (p < 0.01) (fig. 1). There were 8 recurrences in the pidotimod group and 23 in the placebo group. The average length of the episodes (±SD) per group was 17 (±0.59) days between To and T 20 ; 1.3 ± 0.48 days between T 20 and T 50, and 2.2 (± 0.67) days between T 50 and T 80. The placebo figures referring to the same time intervals were 2.1 (± 0.32), 3.3 (± 0.54) and 3.3 (± 0.49) days, respectively. In the pidotimod group, the proportion of subjects who required no antibiotic treatment was 73.7% between To and T 20 ; 94.7% between T 20 and T 50 , and 73.7% between T50 and T 80. The placebo figures referring to the same time intervals were 57.9 and 36.8 %, respectively (fig. 2). At T 80, 12 patients of the pidotimod group and 29 patients of the placebo group were prevented from attending school normally. As regards clinical parameters, it was found that the percentage
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Results
CaredduiBiolchinil Alfano/Zavattini
330
802060-
If. ui
40C Q) ~
20-
a..
20-
20-
80
o
94.7 20-
100
Fig. 1. Proportion of patients showing no recurrences between To and Tso.
Placebo
Pidotimod
%
~
2073.7
Pidotimod Placebo
73.7
%
%
20;J!.
60
J!it: Q)
20-
.~
a.. 20-
20-
20T20
Too Controls
Too
Fig. 2. Proportion of patients who received no antibiotics in the different controls.
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 11/23/2017 3:55:44 AM
20-
A New BRM and Childhood Tonsillitis
331
increase of patients without cough was 84.2 % in the pidotimod group and 31.6% in the placebo group and that of patients without dysphagia was 78.9% in the former and 31.5% in the latter group. Both differences are statistically significant (p < 0.05). The physician in charge rated treatment effectiveness good or very good in 78.9% of the subjects belonging to the pidotimod group and in 15.7% of those of the placebo group. The difference is statistically significant (p < 0.01). Tolerability was good by both physician and parents.
Conclusion
The above results show that treatment with pidotimod of children affected with recurrent tonsillitis is effective both in checking the development of the disease and in reducing the number and severity of recurrences. The sustained effect of pidotimod, which goes well beyond the administration period, the good tolerability and compliance ensured by its oral formulation, fully qualifies this drug as a worthy therapeutic tool to be used whenever immunostimulant treatment in children becomes necessary.
References 22
Pugliese A, Girardello R, Martinelli L, Forno B, Pattarino PL, Biglino A: Valutazione degli effetti di pidotimod su alcuni parametri immunitari. Abstract Book of 6 Congresso della Associazione Italiana di Immunofarmacologia, Firenze 1990, pp 1-110. Illeni MT, Bombelli G, Mailland F, Pattarino PL: Effetto del PGTIlA sulla blastogenesi con mitogeni: studio ex vivo. Atti XXIX Convegno Nazionale di Studi SIITSAICT, Cernobbio 1990, No 36/2, pp 256-260. Auteri A, Pasqui AL, Bruni F, Saletti M: Effect of PGT/IA, a new immunostimulating agent, on some aspects of immune response in vitro study. Abstract Book of Symposium of the International Association of Biological Standardization, Annecy 1991, pp 1-58.
2
3
Dr. G. Zavattini, Medical Department, Poli Industria Chimica SpA, Via Volturno 48, 1-20089 Quinto de' Stampi, Rozzano (Italy)
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0
Pidotimod in the Prophylaxis of Recurrent Acute Tonsillitis in Childhood P. Careddu, A. Biolchini, S. Alfano, G. Zavattini First Department of Pediatrics, University of Milan, and Medical Department, Poli Industria Chimica SpA, Milan, Italy
Recurrent acute tonsillitis is one of the most frequently met with respiratory infections in childhood. Immunologic immaturity is often the cause of this condition while recurrent infections change the cell-mediated immunity. Hence the need for a drug capable of inhibiting this interactive mechanism and stimulating immunity. Pidotimod is a synthetic oral biological response modifier (BRM) (3-L-pyroglutamoil-L-thiazolidin-4-carboxylic acid) proved capable of improving the lymphocytic blastogenesis index and the activation of neutrophil granulocytes as well as increasing the T helper/T suppressor ratio in longlasting treatment [1-3]. In the light of the above considerations, a clinical assessment of pidotimod effectiveness and tolerability in children affected with recurrent acute tonsillitis was deemed to be useful.
Patients and Methods
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 11/23/2017 3:55:44 AM
Thirty-eight outpatients (table 1) of both sexes, aged 2-14 years, were admitted to this randomized double-blind trial versus placebo according to the following inclusion criteria: (a) phlogistic episodes of recurrent acute tonsillitis occurred at least once a month during the past year, and (b) absence of severe hepatic, renal, cardiac or hematopoietic disorders. Patients who received immunostimulants in the 2 months preceding the trial were excluded. Patients were treated at random with either two 400-mg pidotimod sachets or two indistinguishable placebo sachets every day for 20 consecutive days. Clinical tests were made at baseline (To), at the end of the treatment (T 20), at the first (T 50) and the second (T 80) visit of the follow-up period to assess the following parameters:
A New BRM and Childhood Tonsillitis
329
Table 1. Characteristics of patients
Patients Male/female ratio Age, years (x±SD) Age range, years Body weight, kg (x ± SD) Diagnosis Tonsillitis Follicular tonsillitis Pharyngeal tonsillitis Tonsillitis during last winter (x ± SD)
Pidotimod
Placebo
19 10/9 5.8±3.22 2-14 21.8± 10.7
19 10/9 7.3±3.22 3-13 25.3± 10.7
10 I
8 4.5 ± 1.43
8 2 9 4.4± 1.3
the trend of basic disease (number, duration and severity of recurrences during the trial and their effect on antibiotic consumption and capability of attending school); the sign and symptom pattern (dysphagia, nasal stuffiness, cough, pharyngeal hyperemia, tonsillar hypertrophy); laboratory tests showing changes in blood composition, hemopoiesis, hepatic and renal function. At the end of the trial both the physician in charge and the patients were requested to rate the effectiveness and tolerability of the treatment.
The patients showing no recurrences during the treatment and followup period were 12 (63.1 %) in the pidotimod group and 5 (26.3%) in the placebo group. The difference between the two groups (36.8 %) is statistically significant (p < 0.01) (fig. 1). There were 8 recurrences in the pidotimod group and 23 in the placebo group. The average length of the episodes (±SD) per group was 17 (±0.59) days between To and T 20 ; 1.3 ± 0.48 days between T 20 and T 50, and 2.2 (± 0.67) days between T 50 and T 80. The placebo figures referring to the same time intervals were 2.1 (± 0.32), 3.3 (± 0.54) and 3.3 (± 0.49) days, respectively. In the pidotimod group, the proportion of subjects who required no antibiotic treatment was 73.7% between To and T 20 ; 94.7% between T 20 and T 50 , and 73.7% between T50 and T 80. The placebo figures referring to the same time intervals were 57.9 and 36.8 %, respectively (fig. 2). At T 80, 12 patients of the pidotimod group and 29 patients of the placebo group were prevented from attending school normally. As regards clinical parameters, it was found that the percentage
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 11/23/2017 3:55:44 AM
Results
CaredduiBiolchinil Alfano/Zavattini
330
802060-
If. ui
40C Q) ~
20-
a..
20-
20-
80
o
94.7 20-
100
Fig. 1. Proportion of patients showing no recurrences between To and Tso.
Placebo
Pidotimod
%
~
2073.7
Pidotimod Placebo
73.7
%
%
20;J!.
60
J!it: Q)
20-
.~
a.. 20-
20-
20T20
Too Controls
Too
Fig. 2. Proportion of patients who received no antibiotics in the different controls.
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 11/23/2017 3:55:44 AM
20-
A New BRM and Childhood Tonsillitis
331
increase of patients without cough was 84.2 % in the pidotimod group and 31.6% in the placebo group and that of patients without dysphagia was 78.9% in the former and 31.5% in the latter group. Both differences are statistically significant (p < 0.05). The physician in charge rated treatment effectiveness good or very good in 78.9% of the subjects belonging to the pidotimod group and in 15.7% of those of the placebo group. The difference is statistically significant (p < 0.01). Tolerability was good by both physician and parents.
Conclusion
The above results show that treatment with pidotimod of children affected with recurrent tonsillitis is effective both in checking the development of the disease and in reducing the number and severity of recurrences. The sustained effect of pidotimod, which goes well beyond the administration period, the good tolerability and compliance ensured by its oral formulation, fully qualifies this drug as a worthy therapeutic tool to be used whenever immunostimulant treatment in children becomes necessary.
References 22
Pugliese A, Girardello R, Martinelli L, Forno B, Pattarino PL, Biglino A: Valutazione degli effetti di pidotimod su alcuni parametri immunitari. Abstract Book of 6 Congresso della Associazione Italiana di Immunofarmacologia, Firenze 1990, pp 1-110. Illeni MT, Bombelli G, Mailland F, Pattarino PL: Effetto del PGTIlA sulla blastogenesi con mitogeni: studio ex vivo. Atti XXIX Convegno Nazionale di Studi SIITSAICT, Cernobbio 1990, No 36/2, pp 256-260. Auteri A, Pasqui AL, Bruni F, Saletti M: Effect of PGT/IA, a new immunostimulating agent, on some aspects of immune response in vitro study. Abstract Book of Symposium of the International Association of Biological Standardization, Annecy 1991, pp 1-58.
2
3
Dr. G. Zavattini, Medical Department, Poli Industria Chimica SpA, Via Volturno 48, 1-20089 Quinto de' Stampi, Rozzano (Italy)
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 11/23/2017 3:55:44 AM
0
![[Tonsillitis and sore throat in childhood].](/assets/img/hold.png)
