We carried out a longitudinal study to describe the prescription habits for niflumic acid by family paediatricians to see if there is an increased risk of mucocutaneous syndromes in children treated with this drug.
- descrive the use of niflumic acid in a representative sample of Italian children between birth and 14 years of age followed by family paediatricians;
- Estimate the incidence of some mucocutaneous syndromes requiring hospitalisation or treatment in children treated with niflumic acid;
- compare the incidence of mucocutaneous syndromes in children treated with niflumic acid as compared to children treated with control drugs
The study started in September 2001 and was divided into 2 parts.
First phase: collection of prescription data
Second phase: collection and validation of outcomes
A questionnaire was sent to 673 family paediatricians using the same software for at least two years to see if they met the criteria to take part in the study (prescriptions for the drugs being studied, registration of these prescriptions in the database, availability of information on the hospitalisations of interest to the study, interest in taking part in the study). By the 1st March 2002, 278 paediatricians had responded positively to the recruitment criteria and were enrolled in the study. 185 of these sent the data requested within the time frame needed for the study.
The population studied included all children between the ages of 0 and 14 years followed by the 185 participating family paediatricians. 193,727 children (48.1% females), of which 63.4% resident in North Italy were included.
Each child was followed from the 1st January 1998 (start of the study) or frokm the date they joined the family paediatrician (if after 1st January 1998) until May 2001 or until they left the family paediatrician. One patient may have contributed more than one set of data if they received more than one prescription for the drug being studied.
The population being studied included 193 727 children, 45 351 of which had been prescribed at least one of the drugs being studied niflumic acid was the most frequently prescribed drug in children under the age of 5 years (85% of prescriptions).
The incidence of severe mucocutanous reactions (per 100,000 person days) after taking one of the drugs being studied was different in different age groups:
- 13.5 : 0 – 3 years.
- 5.5 : 4 – 6 years
- 1.7 : 7 – 9 years
- 0 : more than 9 years.
Incidence was higher when the drugs were taken in association with antibiotics. Compared to other NSAIDs the relative risk of niflumic acid, age adjusted was 0,5 (95% IC: 0.2-1.3) for severe mucocutaneous reactions and 0.9 (95% IC: 0.8-1.1) for mild mucocutanous reactions (neither statistically significant)
This study shows that the most important factor in predicting risk of developing following treatment with NSAIDs is age.
As niflumic acid was the drug of preference in the smaller children an analysis which does not adjust for age shows an increased but spurious risk of mucocutanous reactions after use of this drug.
The use of niflumic acid does not have any higher risk than the use of other NSAIDs.
Tancredi Giuliano, Bonfigli Emanuela, Caprio Luigia, Del Vomano Elettra, D’Onofrio Vincenzo, Fracassi Americo, Forcina Paolo, Climaco Wilma, Di Gianpietro Tiziana, Lucantonio Ricciardo, Di Saverio Piero, Collacciani Giuseppe, Ferretti Michele, Annibale Domenico.
Falco Pietro, Tambaro Paolo, Mariniello Lorenzo, Bratto Massimo, Marino Antonio, Volpe Giuseppina, Antonucci Eleonora, Di Santo Giuseppe, Basile Paola.
Fabbri Paolo, Reggiani Lamberto, Prodi Miriam, Cappelli Valentina, Barone Roberto, Villani Lina, Gherardi Eugenio, Donati Daniela, Mazzini Franco, Biondi Claudio, Parolini Anna, Bartoli Gianni, Varni Pierfiorenzo, Lusoli Roberto, Faberi Paolo.
FRIULI VENEZIA GIULIA
Rosenwirth Daniela, Fain Simonetta, Lorusso Giuseppe, Andreello Luisa, Cristiani Donatella, Toscano Cristina, Masotti Sergio, De Clara Roberto.
Tusa Antonino, Vailati Marina, Camposarcone Mafalda, Spinelli Bruno, Corrini Luisa Maria, Dusi Daniela, Battilana Maria Pia, De Angelis Monica, Rosignoli Rino, Lietti Giuseppe, Lando Isaia, D’Ambrosa Antonio.
Grelloni Mauro, Tonelli Gabriele, Bari Savio, Piazzini Claudio, Senesi Paolo, Pellegrini Lucia, Lupini Anna, Cicione Giuseppe, Migliori Cesare, Maurizi Maurizio, Toscanelli Angelo, Olimpi Laura Maria, Marconi Carlo, Grugnetti Mirko, Scuppa Ubaldo, Galvagno Andrea, Bollettini Stefano, Braico Giuseppe, De Angelis Massimo, Dichiara Gabriella, Gobbi Costantino, Bravetti Emanuela, Bartolucci Eleonora, Lorenzini Lorella, Budassi Roberto.
Calori Antonella, Fantino Nella, Comaita Fabrizio, Sciolla Nico Maria, Napoleone Maria, Santoro Maria Ausiliatrice, Bruno Eleonora, Caramello Massimo, Pessino Paola, Candido Maurizio, Amadio Franco, Valpreda Andrea, Mauro Giorgio, Bruna Andrea, Corbetta Daniela, Pistone Giovanni, Tavassoli Kaveh, Cagliani Anna, Mondino Mauela, Felicioni Walter, Basso Mirella, Spinelli Franca, Artusio Sergio.
Basoccu Pietro, Lazzari Maura, Pani Paola Maria, Cera Giuseppe Egidio, Rosas Paolo.
Avarello Giovanni, Campo Mario, Vella Rosa Giuseppe, Ceroni Ugo, Lo Bianco Mario, Petrotto Giuseppe, Salamone Pietro, Volpe Concetta, Cumella Antonino, Migliore Patrizia, Alongi Angelo, Moscato Vincenzo, Speciale Sergio.
Rolla Mario, Pucci Catia, Frontini Enrico Luciano, Fonsati Mario, Barsotti Ferruccio, Massai Ugo.
Semenzato Flavio, Spanevello Walter, Zanette Marco, Fama Mario, Sardei Daniela, Beccaro Francesca, Miglioranzi Giampaolo, Brusaterra Ivana, Naso Immacolata, Girotto Silvia, De Santi Marilena, Grillone Giuseppe, Esposito Giorgio, Bucolo Carmelo, Risdonne Giampaolo, Marchese Paolo, Andreotti Maria Francesca, Silvan Carla, Pasinato Angela, Toderini Luisa, Cozzani Sandra, Giancola Giuseppe, Boscolo Roberto, Cantarutti Luigi, Fusco Fabrizio, Borghesani Marisa, Bonati Saverio, Montini Camilla, Tamassia Gianni, Girgenti Calogero, Baldin Francesco, Parolini Gianpaolo, Saretta Luigi, Fornasari Silvia, Signorini Rita, Iuliano Maria, Tapparello Gianantonio, Gobbi Patrizia, Lemma Carlo, Toffol Giacomo, Dal Lago Lorenzo, Pittarello Daniele, Baggiani Adriana, Dell’Antonia Fabio, Brutti Paolo¸ Ieva Angela, Chirco Maria, Sassolino Stefania, Milani Massimo, Bonaiuto Francesco, Righetti Andrea, Zuccolo Maria Luisa, Neidhart Carlo, Mattiazzo Paola, Marinucci Nicoletta, Mastroprimiano Silvana, Doria Mattia, Allegri Paolo Martino, De Marchi Anna Maria, Fabriano Giovanni, Spacagna Francesco.
Miriam C.J.M. Sturkenboom, Alfredo Nicolosi, Luigi Cantarutti, Salvatore Mannino, Gino Picelli, Antonio Scamarcia, Carlo Giaquinto, for the NSAIDs Paediatric Research Group
Pediatrics; 2005, 116: 26-33
The study was partially funded by UPSA spa.