Real World Data on the Utilization Pattern and Safety Profile of Infliximab Originator Versus Biosimilars in Italy: A Multiregional Study

Abstract

BackgroundIn recent years, several biosimilar drugs, including those of infliximab, have obtained marketing authorization from the European Medicines Agency (EMA). Given the peculiarity of the safety profile of biological medical products (originator and biosimilars), the evaluation of their tolerability represents an important component of pre-marketing and post-marketing clinical development. For example, infliximab products may cause adverse drug reactions (ADRs) including acute infusion reactions, delayed hypersensitivity reactions, and loss of efficacy, as a direct consequence of immunogenicity. Therefore, specific contraindications, special warnings and precautions have been introduced in the infliximab Summary of Product Characteristics (SPC).ObjectiveThe aim was to assess the magnitude of preventable ADRs in individual case safety reports (ICSRs) having infliximab as a suspected drug across Italy (using the spontaneous reporting systems), and the probability of reporting infections, infusion reactions, lack of efficacy, and hypersensitivity for originator and biosimilars of infliximab.MethodsWe analyzed ADRs reported across the 2015–2017 period in the databases of five Italian regions: Campania, Lombardy, Sicily, Tuscany, and Veneto. Preventability of ADRs was assessed using the P-method. To compare the probability of reporting infections, infusion reactions, lack of efficacy, and hypersensitivity as ADRs as opposed to other types of ADRs between originator and biosimilars of infliximab, we used the reporting odds ratio (ROR). For descriptive purposes, the number of ICSRs involving infliximab, the number of infliximab vials distributed in the aforementioned Italian regions and the relative reporting rate stratified by semester were reported.ResultsFrom October 2015 to October 2017, 459 ICSRs reported infliximab as a suspected drug (222 ICSRs related to infliximab originator and 237 to infliximab biosimilars). In the same period, 81,906 vials of infliximab were distributed, resulting in a reporting rate of six ICSRs/1000 vials. Overall, 34 cases (7.41%) were categorized as preventable. The most frequently detected critical criteria were “documented hypersensitivity to administered drug or drug class,” “inappropriate prescription for patient’s underlying medical condition” and “incorrect dose.” Biosimilars had, in adjusted analyses, an increased probability of being reported as suspected in ICSRs reporting infusion reactions (ROR 4.09; 95% confidence interval [CI] 1.26–13.32) when compared to Remicade®. On the contrary, they had a decreased probability of being reported as suspected in ICSRs reporting infections or lack of efficacy (ROR 0.33; 95% CI 0.12–0.89; ROR 0.35; 95% CI 0.20–0.61).ConclusionOur study demonstrates that, along with a rapid increase in the utilization of infliximab biosimilars across Italy, there was also an increase in reporting ADRs induced by infliximab biosimilars. Of the reported ADRs, 7.4% were considered preventable. In adjusted analyses, infliximab biosimilars were shown to have ...

Quinolones-Induced Musculoskeletal, Neurological, and Psychiatric ADRs: A Pharmacovigilance Study Based on Data From the Italian Spontaneous Reporting System

“…ICSRs were screened among those reported in the Campania spontaneous reporting system from January 2001 to April 2019. matter of fact, the risk of ADR for women of developing an ADR is 1.5-to 1.7-fold higher compared to men (Rademaker, 2001;Zopf et al, 2008). This was previously reported for other drug classes-induced ADRs in other studies (Scavone et al, 2018b;Mascolo et al, 2019). Furthermore, Tomé AM et al found a higher prevalence of quinolones-induced ADRs in female patients (Tomé and Filipe, 2011).…”

Infliximab biosimilar CT-P13 is effective and safe in treating inflammatory bowel diseases: a real-life multicenter, observational study in Italian primary inflammatory bowel disease centers

“…This result deserves an adequate analysis. From October 2015 to October 2017, a rapid increase in the utilization of biosimilar IFX CT-P13 was recorded across Italy [33]. However, this increase was also associated with an increase in the reports of AE induced by IFX biosimilars [33].…”

“…From October 2015 to October 2017, a rapid increase in the utilization of biosimilar IFX CT-P13 was recorded across Italy [33]. However, this increase was also associated with an increase in the reports of AE induced by IFX biosimilars [33]. This seems to contrast with a recent study by Gonçalves et al , who found a similar antigenic profile for IFX originator and IFX biosimilar CT-P13 [34].…”

Biopharmaceuticals safety perception in Slovakia: considerations and real-life pharmacovigilance data

“…With a rapid increase in the utilization of biosimilars, there is also an increase in reporting ADRs induced by respective agents. In the frame of a recently published Italian real-world data analysis, infl iximab biosimilars were shown to have an increased probability of being reported as suspected drugs in infusion reactions along with a decreased probability of being reported as suspected drugs in cases of lack of effi cacy or infection (25). We must admit that the perceptiveness of the Slovak healthcare community towards the reported ADR remains still low, especially, when compared to other European countries (26,27).…”