P515 Infliximab desensitization in patients with Inflammatory Bowel Diseases: a safe therapeutic alternative
Hammoudi, N.(1)*;Hassid, D.(1);Bonnet, J.(1);Tran Minh, M.L.(1);Baudry, C.(1);Chedouba, L.(1);Vauthier, A.(1);Gornet, J.M.(1);Allez, M.(1);
(1)APHP Saint Louis, Gastroenterology, Paris, France;
Background
Infliximab (IFX) is a humanized monoclonal anti-TNF antibody widely used for the treatment of Inflammatory Bowel Diseases (IBD). Hypersensitivity reactions (HSR) to the administration of the drug are not rare. Their occurrence usually leads to permanent 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. Clinical data on IBD were collected. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after were collected. Clinical outcome and recurrence of HSR were evaluated.
Results
From 2005, 27 patients (Female: 18 (66%), Median age at IBD diagnosis: 18.1 (15.6-28.2)) were included. Among these 27 patients, 26 (96%) had Crohn’s Disease, 17 (62%) a history of surgery, 14 (52%) an ileal disease location and 7 (26%) were smokers. It was an immediate HSR in most patients, classified as severe (n=13) or moderate (n=12), and a delayed HSR in only 2 patients. Eleven (41%) patients were treated with immunosuppressants as combination therapy at time of HSR. In most cases (n=18, 66%), HSR occurred at IFX reintroduction after a drug interruption, and in most of these cases after one or two infusions. For 9 (33%) patients, HSR occurred during a maintenance treatment with IFX after a median time of 38 months with 5 moderate and 4 severe reactions.
Desensitization was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants as combination therapy.
IFX was well tolerated, without recurrence of HSR in 19 (70%) patients, and 12 had a clinical response at 6 months. Eight were still treated with IFX (30%) at 1 year. Eight (30%) patients presented a HSR at first (n=2), second (n=4) or third (n=2) IFX perfusion. Five were moderate with only cutaneous manifestations and 3 were severe. None led to intensive care unit transfer or death. All led to definitive drug discontinuation.
Female gender and young age at desensitization were significantly associated with long term continuation of IFX (p=0.05 and p=0.03 respectively).
ADA and IFX trough levels were available for 14 patients at time of desensitization. All except 2 had ADA. Among patients who were treated with IFX for a long-term period, 7 had drug levels available at desensitization and 6 months later. All had ADA at baseline. At 6 months, four reduced their level of ADA, 2 had no ADA and 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.