Intensive monitoring of adverse drug reactions in patients receiving pharmacological treatments for rheumatoid arthritis and other rheumatologic diseases, with particular focus on biotechnological drugs: The ASTRAGALUS study

Objectives: ASTRAGALUS is a three-year observational study, which has been started in 2010 in Tuscany to investigate the incidence and clinical features of adverse events (AEs) in patients receiving biologic drugs for rheumatologic disorders. Methods: Patients are being enrolled in four Rheumatology Units at the Hospitals of Pisa, Firenze, Siena and Arezzo. Medical records of (table present) eligible patients have been checked to collect retrospective information on their clinical history (adverse events, drug treatments and dose regimens, concomitant therapies, disease course, laboratory data). Patients will be then followed-up prospectively for up three years through scheduled visits. All diseases and adverse events are classified by MedDRA Term dictionary. Patients currently or formerly receiving treatments with biologic drugs (infliximab, etanercept, adalimumab, rituximab, tocilizumab, abatacept and anakinra) have been requested to read and sign informed consent to participate to the study. AEs are classified as adverse drug reactions (ADRs) when they scored at least as possible upon evaluation by Naranjo algorithm for causality assessment. The present analysis reports the first 10 months of observation. Results: Patients recorded in the study database were 396 (259 females; mean age: 54.90 ± 13.78). 444 AEs have been recorded, 35 of which were classified as serious. Patients with at least one AE were 190, and 120 were classified as having experienced ADRs. Table I summarizes the number of patients with at least one ADR and their frequency in subgroups receiving the different biologic drugs under evaluation (Table I). The AEs more commonly recorded in the database were: inflammatory condition (65 cases), oropharyngeal pain (52), cough (50), infectious disease (47), fever (37), transaminase increased (31), diarrhea (24), reaction related to infusion (19), dysuria (18) and leukopenia (11). Serious ADRs associated with biologic treatments were: angioedema, hemorrhagic cystitis, lung infection, Guillaine-Barre syndrome and salivary gland cancer for adalimumab; Prinzmetal angine for tocilizumab; squamous cell carcinoma, skin ulcer, myocardial infarction and pericardial effusion for etanercept; respiratory failure for rituximab; pericarditis, pleural effusion and infusion reaction for infliximab. Conclusions: Overall, according to the present preliminary analysis, biologic medications are frequently associated with the development of adverse reactions, which are mild to moderate in severity. However, serious reactions may also occur. Our data confirmed also the development of infectious diseases and infusion reactions as prominent issues related to these therapies. Accordingly, a careful monitoring of patients receiving biologic drugs is required for an early identification and management of potentially harming adverse effects.