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.

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of 5 mg folic acid (FA) daily and serum concentrations of folate, unmetabolized folic acid (UMFA), interleukin (IL)-6, IL-8, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α); and mRNA expression of dihydrofolate reductase (DHFR), methylene tetrahydrofolate reductase (MTHFR), IL8, IFNG and TNFA genes. Total serum folate and folate forms were measured in 27 patients with HS (21 users [HS-U] and 6 non-users [HS-NU] of supplemental FA) and 54 healthy controls not consuming 5 mg/day supplemental FA. Each patient was matched to two controls based on age, sex and body mass index. The mononuclear leucocyte mRNA expression of relevant genes and their products were determined. Serum folate, UMFA, 5-methyl-tetrahydrofolate (5-methyl-THF) and tetrahydrofolate (THF) concentrations were significantly higher in HS-U compared with matched healthy controls (p<0.001, n=42). HS-NU had lower serum folate concentrations than matched healthy controls (p=0.044, n=12). HS-U and HS-NU presented similar hematological and biochemical markers profiles. No differences were found between HS-U and HS-NU for cytokine serum concentrations and mRNA expression genes. DHFR mRNA expression was higher in HS-U than in HS-NU. The use of high daily doses of FA for treatment of patients with HS may be excessive and is associated with elevated serum UMFA and elevated DHFR mRNA expression. It is not known whether long-term high-dose FA use by patients with HS might have adverse health effects.

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