Adverse Events in Patients With Rheumatoid Arthritis and Psoriatic Arthritis Receiving Long-Term Biological Agents in a Real-Life Setting

Abstract

Background: Biological agents used for the treatment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are associated with serious adverse effects (SAEs). Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third line therapies due to a relative lack of long-term safety data. Objective: To determine the frequency and severity of adverse effects associated with the long-term use of biologics in the treatment of PsA and RA, and possible risk factors for such events in a real-life setting. Methods: We conducted a longitudinal study in PsA and RA patients only taking long-term biological agents from 2003 to 2011. Sources of information included dispensing pharmacy data and interviews with patients. Research staff conducted telephone interviews with patients inquiring about any apparent medication-related adverse drug reactions (ADRs) or SAEs. ADR/SAE’s data was based on pharmacy reports. We conducted a multivariate analysis to identify the factors associated with the risk of ADRs. Results: Of the 305 patients identified, we interviewed 268 patients. Most of these were taking adalimumab 127 (47.4%), 52 (19.4%) etanercept, 42 (15.7%) infliximab, 25 (9.3%) rituximab, 10 (3.7%) abatacept, 9 (3.4%) efalizumab, and 3 (1.1%) tocilizumab. Of the 268 patients, 116 (43.3%) experienced one or more adverse events related to biological agents with 1.6 events per patient, and of these 29 (25%) experienced one or more SAEs, with majority subjected to hospitalizations. The most frequently reported ADRs were administration site reactions as observed in 73 patients (27.2%), infections in 30 patients (11.2%), effects on nervous system in 22 patients (8.2%), and 15 (5.6%) patients withdrew due to ADRs. The use of rituximab was related with less risk of ADR [PR 0.42, 95% CI 0.18–0.96; p = 0.04] than other agents. No other predisposing factors were associated with risk of ADR. The monitoring of patients (medical consultation and laboratory test) was only completed by 48 patients (30.4%). Conclusion: These data showed the early biological experience in Brazil that were associated with ADRs, withdrawals due to ADRs and SAEs. The quantification of adverse effects (serious or nonserious) considering close monitoring and patients’ perceptions are increasingly important for future decision-making.

Adverse drug reactions associated with the use of biological agents

“…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].…”

“…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]. Death does not correspond to an adverse event but rather to a fatal outcome that can also be explained by the underlying disease of the patient.…”

“…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.…”

“…The incidence in our study was determined in a general manner for all ADRs, while the Spanish study only considered serious ADRs [19]. In Brazil, in patients with rheumatoid arthritis and psoriatic arthritis, 55.2% and 19.8% of ADRs were secondary to adalimumab and etanercept, respectively [22]. In Spain, in patients with rheumatoid arthritis, 35.1% and 21.6% of ADRs were due to adalimumab and etanercept, respectively [13].…”

Editorial: New Horizons in Health-Promoting Technologies: From Development to Rational Use

“…New technologies are registered based on controlled and randomized clinical trials, in which, in most cases, they fail to capture important safety results that only appear in real-life studies ( Lopes et al., 2014 ; Fulone et al., 2018 ; De Carmago et al., 2019 ). In addition, in the case of new cancer medicines, often licensed on the basis of limited information, which can cause concern and wasted resources ( Pontes et al., 2020 ).…”