Immunogenicity of Infliximab Among Patients With Behçet Syndrome: A Controlled Study

Abstract

BackgroundImmunogenicity of tumor necrosis factor alpha inhibitors (TNFis) has been recognized as an important problem that may cause loss of efficacy and adverse events such as infusion reactions. TNFis are being increasingly used among patients with Behçet syndrome (BS) and scarce data exist on this topic.ObjectiveWe aimed to investigate the prevalence of anti-infliximab (IFX) antibodies in patients with Behçet syndrome together with suitable controls.MethodsWe collected serum samples from 66 consecutive Behçet syndrome patients (51 M, 15 F, mean age 37 ± 9 years) who were treated with IFX. Additionally, similarly treated 27 rheumatoid arthritis, 53 ankylosing spondylitis, 25 Crohn’s disease patients, and 31 healthy subjects were included as controls. Samples were collected just before an infusion, stored at −80°C until analysis, and serum IFX trough levels and anti-IFX antibodies were measured by ELISA. We used a cut-off value of 1 μg/ml for serum IFX trough level, extrapolating from rheumatoid arthritis studies.ResultsAnti-IFX antibodies were detected in four (6%) Behçet syndrome, five (18.5%) rheumatoid arthritis, three (12%) Crohn’s disease, and one (2%) ankylosing spondylitis patient. The median serum IFX trough level was significantly lower in patients with anti-IFX antibodies compared to those without antibodies [2.32 (IQR: 0.6–3.6) vs. 3.35 (IQR: 1.63–5.6); p = 0.019]. The serum IFX trough level was lower than the cut-off value in 6/13 (46%) patients with anti-IFX antibodies and in 25/158 (16%) patients without anti-IFX antibodies (p = 0.015). Among the four Behçet syndrome patients with anti-IFX antibodies, two experienced relapses and two had infusion reactions.ConclusionsImmunogenicity does not seem to be a frequent problem in Behçet syndrome patients treated with IFX, but may be associated with relapses and infusion reactions, when present.

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

“…This drug, with anti-inflammatory and immunosuppressive functions, also has important collateral effects, especially in pediatric age since it blocks growth, delays bone development, and causes weight gain and mood instability. Therefore, the identification of cytokines as therapeutic targets has great relevance: examples of this are canakinumab and anakinra, inhibitors of soluble IL-1β and its receptor, respectively; infliximab and certolizumab, which bind TNF-α; tocilizumab, which blocks IL-6 ( Table 1 ) [ 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , …”

Recent Insights into the Management of Behçet Syndrome

“…Immunogenicity of infliximab in BS patients was evaluated in a controlled study. 51 Serum samples from 66 consecutive BS patients (51 M, 15 F, mean age 37±9) treated with infliximab were compared with similarly treated rheumatoid arthritis, ankylosing spondylitis and Crohn's disease patients. Anti-infliximab antibody levels in BS (6%) were lower than rheumatoid arthritis (19%) and Crohn's disease (12%) but slightly higher than ankylosing spondylitis (2%).…”