Safety and Tolerability of Infliximab Therapy: Suggestions and Criticisms Based on Wide Clinical Experience

Abstract

Infliximab, an IgG1 monoclonal chimeric antibody against tumor necrosis factor (TNF)-α, represents the main biological drug employed for the treatment of several immuno-mediated inflammatory disorders. Infliximab infusion can be complicated by clinically heterogeneous adverse reactions, potentially interfering with the course of treatment. We analysed the adverse events recorded in 49 patients affected by different chronic inflammatory disorders (rheumatoid arthritis, seronegative spondiloarthritis, Behçet's disease, Wegener's granulomatosis, Churg-Strauss' syndrome, Cogan's disease) who were receiving a total of 709 infliximab infusions, in order to correlate the development of infliximab reactions and their features to some potential risk factors. We displayed a lower frequency of infusion reactions (1.5%; 11 out of 709 infusions) than those previously reported. However, patients suffering from rheumatoid arthritis and/or patients who underwent re-treatment after a long period, showed a higher prevalence of infliximab-related reactions. In conclusion, in our experience infliximab treatment is rarely complicated by adverse reactions which are, more importantly, almost always mild. Some good clinical practices, such as the low rate of infusion, pre-treatment with anti-histamine and prednisone in all patients, chronic immunosuppressive therapy and avoidance of long intervals between infusions may represent a combined useful strategy to reduce the frequency of infliximab reactions and to increase safety.

Long-Term Anti-TNF-α Treatments Reverse the Endothelial Dysfunction in Rheumatoid Arthritis: The Biological Coherence between Synovial and Endothelial Inflammation

“…Remarkably, the infliximab-treated patients who exhibit a loss of efficacy manifested a restored response after they were moved to adalimumab therapy (18,(21)(22).…”

“…Furthermore, the finding of a sudden decrease or absence of FMD may be regarded as suggestive of a pathophysiological role of other cytokines, in particular IL1, in the presence of a cytokine network unbalance, concurrent with the TNFa block given by the biological agent (20)(21)(22)(23).…”

Immediate adverse reactions to biologicals: from pathogenic mechanisms to prophylactic management

“…Taking a thorough history, particularly including atopic status and any previous allergic reactions, is one of the most useful risk-assessment tools in drug allergy. However, a similar prevalence of atopy and previous adverse drug reactions in reactive and unreactive patients was seen [6].…”

“…In fact, with reference to rituximab, whereas patients with B cell malignancies and RA developed rituximab-specific antibodies in 1 and 4%, respectively [21], ADAs have been reported in about 25% of patients with primary Sjogren's syndrome and antineutrophil cytoplasmic auto-antibody-associated vasculitis and in up to 40% of patients with systemic lupus erythematosus (SLE) [22][23][24]. Concerning infliximab, we observed a higher incidence of ATI in patients suffering from RA (62.5%) than in patients with seronegative spondyloarthropaties (SpA) or vasculitis (37.5%) [6]. The reason for the variable occurrence of ADAs in different disorders is unclear but may be related to the pathogenic mechanisms of the disease itself.…”

Immunotherapies in Dermatologic Disorders

“…However, the probability and intensity of adverse reactions tends to increase with higher dosage. 96 Infliximab is approved for the treatment of psoriasis and psoriatic arthritis. Patients with psoriasis can achieve significant improvement with this immunotherapy.…”