Immunogenicity of Infliximab Among Patients with Behcet’s Syndrome: A Controlled Study

Sinem Nihal Esatoglu¹, Fatma Nihan Akkoc¹, Yesim Ozguler¹, Fatma Ozbakir², Okan Kadir Nohut², Dilsen Cevirgen³, Vedat Hamuryudan¹, Ibrahim Hatemi⁴, Aykut Ferhat Celik⁵, Hasan Yazici¹ and Gulen Hatemi¹, ¹Istanbul University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey, ²Istanbul University, Cerrahpasa Medical Faculty, Central Research Laboratory, Istanbul, Turkey, ³Istanbul University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of and Rheumatology, Istanbul, Turkey, ⁴Istanbul University, Cerrahpasa Medical School, Istanbul University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Gastroenterology, Istanbul, Turkey, ⁵Istanbul University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Gastroenterology, Istanbul, Turkey

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: Ankylosing spondylitis (AS), Behcet's syndrome, Crohn's Disease, immune response and infliximab

Session Information

Date: Tuesday, November 7, 2017

Title: Vasculitis Poster III: Other Vasculitis Syndromes

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

Immunogenicity of anti-TNFs has been recognized as an important problem that may cause loss of response and adverse events such as infusion reactions. We aimed to investigate the prevalence of anti-drug antibodies against infliximab (IFX) in patients with Behçet’s syndrome (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 receiving IFX. IFX was used for severe 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^oCuntil analysis, and serum IFX trough levels and anti-IFX antibodies were measured by ELISA at the same time. We reviewed the charts of these patients regarding demographic and clinical characteristics, concomitant DMARDs, the number of IFX treatment cycles, responsiveness to IFX and allergic reactions. We used a cut-off value of 0.5 μg/mL for serum IFX trough level, extrapolating from RA studies. After serum sampling, we continued to follow up patients regarding allergic reactions and treatment efficacy.

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. During follow up, 2/4 BS patients with anti-IFX antibodies had flares. Allergic reactions occurred in 9 (14%) BS, 6 (22%) RA, 5 (20%) CD, and 4 (7.5%) AS patients. 3/5 RA patients and 3/3 CD patients who experienced an allergic reaction had anti-IFX antibodies whereas none of BS and AS patients did.

Concomitant DMARDs were used in 46 (74%) BS, 17 (67%) RA, 22 (84%) CD, and 7 (13%) AS patients. Overall, 6 (46%) patients with anti-IFX antibodies were not on DMARDs. The median serum IFX trough level was significantly lower in patients with anti-IFX antibodies compared to those without antibodies (0.17 (IQR: 0.08-0.28) vs 0.12 (IQR: 0.03-1.18; p=0.042). The serum IFX trough level was lower than the cut off value in all of the 13 patients with anti-IFX antibodies and in 89% of patients without anti-IFX antibodies (p=0.64).

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 0.5 μg/mL before IFX and above 0.5 μg/mL at week 2 in all of these 5 patients.

Conclusion:

BS patients had a lower frequency of anti-IFX antibodies compared to RA and CD patients and similar to AS patients. This might be related to the similar comparative low B cell activity in these 2 conditions. Due to the small number of BS patients with anti-IFX antibodies, we could not conclude on the effect of immunogenicity on the treatment response. The low serum IFX levels even in patients without anti-IFX antibodies and good drug response deserves further attention.

Disclosure: S. N. Esatoglu, None; F. N. Akkoc, None; Y. Ozguler, None; F. Ozbakir, None; O. K. Nohut, None; D. Cevirgen, None; V. Hamuryudan, None; I. Hatemi, None; A. F. Celik, None; H. Yazici, None; G. Hatemi, None.

To cite this abstract in AMA style:

Esatoglu SN, Akkoc FN, Ozguler Y, Ozbakir F, Nohut OK, Cevirgen D, Hamuryudan V, Hatemi I, Celik AF, Yazici H, Hatemi G. Immunogenicity of Infliximab Among Patients with Behcet’s Syndrome: A Controlled Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/immunogenicity-of-infliximab-among-patients-with-behcets-syndrome-a-controlled-study/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunogenicity-of-infliximab-among-patients-with-behcets-syndrome-a-controlled-study/