FRI0477 Immunogenicity of infliximab among patients with behcet’s syndrome: a controlled study

Background Immunogenicity of anti-TNFs has been recognised as an important problem that may cause loss of efficacy and adverse events such as infusion reactions. Anti-TNFs are being increasingly used among patients with Behcet’s syndrome (BS). Objectives We aimed to investigate the prevalence of anti-drug antibodies against infliximab (IFX) in patients with BS together with controls. Methods We collected serum samples from 66 consecutive BS patients (51 M, 15 F and mean age 37±9 years) who were treated with IFX. IFX was used for eye involvement in 43, vascular involvement in 12, nervous system involvement in 8 and arthritis in 2 patients. Additionally, 53 ankylosing spondylitis (AS), 25 Crohn’s disease (CD) and 27 rheumatoid arthritis (RA) patients, and 31 healthy subjects were included as controls. We included patients who had received at least 4 cycles of IFX. Samples were collected just before an infusion, stored at −80 o C until analysis, and serum IFX trough levels and anti-IFX antibodies were measured by ELISA at the same time. We used a cut-off value of 1 µg/mL for serum IFX trough level, extrapolating from RA studies. After serum sampling, we continued to follow up patients. Results Anti-IFX antibodies were detected in 4 (6%) BS, 5 (18.5%) RA, 3 (12%) CD, and 1 (%2) AS patient, and in none of the healthy subjects. The mean number of IFX cycles was 19±14 in BS, 21±13 in RA, 19±21 in CD, and 33±18 in AS patients. Allergic reactions had occurred in 9 (14%) BS, 6 (22%) RA, 5 (20%) CD, and 4 (7.5%) AS patients. 3/6 RA patients and 3/5 CD patients who had experienced an allergic reaction had anti-IFX antibodies whereas none of BS and AS patients did. 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 patients with anti-IFX antibodies and in 25/158 without anti-IFX antibodies (46% vs 16%; p=0.015). We were able to get samples before at least 2 consecutive infusions in 27 BS patients and the presence of anti-IFX antibodies was consistent across the samples in all of these patients. We were able to get samples before the infusion and at week 2 in 5 BS patients. Serum IFX level was below 1 µg/mL before IFX and above 1 µg/mL at week 2 in all of these 5 patients. During a median follow up of 1.5 years, 2/4 BS patients with anti-IFX antibodies had flares. Among the 62 patients without anti-IFX antibodies, 49 are still on IFX and IFX was stopped due to remission in 12 and due to infusion reaction in one patient. Overall, 5 infusion reactions occurred during the follow up (4 without anti-IFX antibodies and 1 with anti-IFX antibodies; 6.5% vs 25%). Conclusions Immunogenicity does not seem to be an important problem in BS patients treated with IFX. The frequency of anti-IFX antibodies was lower than RA and CD patients. This might be related to concomitant immunosuppressive and corticosteroid use among BS patients. The presence of anti-IFX antibodies may not be associated with efficacy loss in BS. However, longer follow-up is needed to make that statement as BS has a relapsing-remitting course. Disclosure of Interest None declared