Infliximab desensitization in patients with inflammatory bowel diseases: a safe therapeutic alternative

Abstract

Background

Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR.

Methods

We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated.

Results

From 2005 to 2020, 27 patients (Crohn’s Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first (n = 2), second (n = 4) or third (n = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX.

Conclusion

IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics.

What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation.

What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity.

How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug.

Keywords:

• Anti-TNF
• infliximab
• hypersensitivity reaction
• desensitization

Author contributions

MA designed the study and interpreted the data; NH: performed the statistical analyses, interpreted the data and wrote the manuscript; DH collected the data and wrote the manuscript; PH performed the trough levels and anti-drug antibodies dosages, AV collected the data, JB, MLTM, CB, NL, TA, JMG, JB and LC included patients and reviewed the final version of the manuscript. All authors read and approved the final manuscript.

Disclosure statement

NH has served as a consultant/advisory board member to Abbvie, Janssen and Lilly and as speaker for Galapagos and Takeda. MA has served as a consultant/advisory board member to Abbvie, Amgen, Biogen, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Celsius, Celltrion, Egle Therapeutics, Endpoint health, Ferring, Galapagos, Genentech, IQVIA, Janssen, Lilly, Novartis, Pfizer, Roche, Takeda, Tillots; speaker for CME activities for Abbvie, Galapagos, Genentech, Janssen, Pfizer, Roche, Takeda, Tillots; grant support from Janssen, Takeda, Genentech/Roche. MLTM received honoraria from Abbvie and Janssen. JMG has been a speaker and/advisory board member for Abbvie, Amgen, Celltrion, Takeda, Janssen and Sanofi Genzyme. DH, JB, CB, AV, LC, PH, NL, TA have no disclosure related to this work.

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.