Safety Profile of Biologics Used in Rheumatology: An Italian Prospective Pharmacovigilance Study

Abstract

Post-marketing surveillance activities are essential to detect the risk/benefit profile of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthritis. The aim of this study was to evaluate adverse events (AEs) in patients treated with bDMARDs in rheumatology during a prospective pharmacovigilance study from 2016 to 2018. Descriptive statistical analyses were performed to evaluate bDMARDs-related variables of patients without AEs/failures vs patients with AEs and failures. The risk profile among biologics was assessed by comparing patients treated with each bDMARD to patients treated with etanercept. A total of 1155 patients were enrolled, mostly affected by rheumatoid arthritis (46.0%). AEs and failures were experienced by 8.7% and 23.3%, respectively. The number of comorbidities significantly influenced the onset of AEs, while anxiety-depressive, gastrointestinal disease, and fibromyalgia influenced onset of failures. The probability of developing an AE was significantly lower in patients treated with secukinumab, while the probability of developing treatment failure was significantly lower in patients treated with golimumab, secukinumab and tocilizumab. A total of 216 AEs were reported (25.5% serious), mostly regarding infections (21.8%), musculoskeletal (17.6%) and skin (16.2%) disorders. Serious AEs included neutropenia (12.7%), lymphocytosis (9.1%) and uveitis (7.3%). The obtained results revealed known AEs but real-world data should be endorsed for undetected safety concerns.

Adverse drug reactions associated with the use of biological agents

“…ADRs associated with biotech drugs occur more frequently in women, as documented in other studies conducted in Spain (82.9%) [13], the United States (75.5%) [14] and Italy (54.3-71.3%) [4,15], in agreement with the present finding. This is probably because many of the pathologies for which biotech drugs are used have a known predominance in women, including autoimmune diseases such as rheumatoid arthritis [16,17] or oncological diseases [18], which expose women to a greater probability of use and of developing ADRs.…”

“…In the present study, the main biotech drugs related to ADRs were adalimumab and etanercept, in agreement with other studies [13,15,22], but the incidence per 100 patients per year was higher than that reported in Spain in patients with rheumatoid arthritis (8.1 for adalimumab and 5.1 for etanercept) [19]. The incidence in our study was determined in a general manner for all ADRs, while the Spanish study only considered serious ADRs [19].…”

“…70.2% vs. bDMARD: 17.5%) and 12.3% were type B (sDMARD: 8.1% vs. bDMARD: 4.2%); no other ADR types were observed [25]. In addition, according to severity, 22.6% of the reports were classified as serious, consistent with what was found in Italy (9.8-25.5%) [15,23], Japan (18.5-23.4%) [20,26], Spain (21.7%) [19], Brazil (25.0%) [22] and Korea (32.3%) [12]. Among severe reactions, the possibility of developing cancer, infections, hypersensitivity reactions and major cardiovascular events is described in the literature [10,12,14,19,22], and fatalities can also occur, which in this report corresponded to 0.1% of all ADRs, a rate lower than that documented in another study [27].…”

“…The ADRs most documented in different studies are those related to infections [14,15,[19][20][21], general manifestations or those associated with the administration of biotech drugs [12,22,23] and those related to the skin or subcutaneous tissues [4,12,23,24]. However, the present study found that the most common ADRs were those related to the respiratory tract, diverging with what was found in other studies where their frequency was much lower (16.8 vs. 3.8-10.8%) [4,12,24], probably because we included in this category infections such as pneumonia and bronchitis, among others, which increased the proportion of respiratory tract-related ADRs.…”

“…In Spain, in patients with rheumatoid arthritis, 35.1% and 21.6% of ADRs were due to adalimumab and etanercept, respectively [13]. In Italy, Barbieri et al studied patients with inflammatory arthritis and found that 27.3% and 19.0% of ADRs were due to etanercept and adalimumab, respectively [15]. However, many studies also report a high proportion of ADRs secondary to infliximab [3,19,27], which was not observed in the present study due to the low use of this drug in Colombia.…”