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REMICADE - Delayed Hypersensitivity Reactions

Last Updated: 11/03/2021


  • REMICADE is contraindicated in patients with previous severe hypersensitivity reaction to infliximab or any of the active ingredients of REMICADE or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness).1
  • REMICADE has been associated with hypersensitivity reactions that vary in their time of onset and required hospitalization in some cases. Most hypersensitivity reactions (including anaphylaxis, urticaria, dyspnea, and/or hypotension), have occurred during or within 2 hours of REMICADE infusion.1
  • In some cases, serum-like reactions have been observed in patients after initial REMICADE therapy (ie, as early as after the second dose), and when REMICADE therapy was reinstituted following an extended period without REMICADE treatment. Symptoms associated with these reactions include fever, rash, headache, sore throat, myalgias, polyarthralgias, hand and facial edema and/or dysphagia. These reactions were associated with a marked increase in antibodies to infliximab, loss of detectable serum concentrations of infliximab, and possible loss of drug efficacy.1
  • REMICADE should be discontinued for severe hypersensitivity reactions.1
  • In Ps studies, approximately 1% of REMICADE-treated patients experienced a possible delayed hypersensitivity reaction, generally reported as serum sickness or combination of arthralgia and/or myalgia with fever and/or rash. These reactions generally occurred within 2 weeks after repeat infusion.1
  • Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions.1
  • Reports of delayed hypersensitivity reactions (DHR) or serum sickness-like reactions in patients receiving REMICADE have also been described in the published literature.2-4


Retrospective Studies

Bonner et al (2004)2 retrospectively reviewed the adverse reactions in 75 patients with Crohn’s disease (CD) to determine if time interval to follow-up REMICADE infusions was associated with an increased risk of delayed hypersensitivity reactions or other infusion reactions.

  • After an REMICADE-free interval of ≥8 weeks, the first follow-up infusion was assessed for reactions.
  • A total of 56 patients received REMICADE infusions (dose not reported) at 0, 2, and 6 weeks. Twelve patients received 1 initial infusion, and 7 patients received 2 initial infusions. Of these patients, 16 received maintenance therapy every 8 weeks, while 59 patients received follow-up infusions on an as needed basis, varying from 3-55 months. Eleven (14.7%) patients experienced DHR and 8 (10.7%) had infusion reactions.
  • The increasing time interval between the infusions increased the risk of DHR, however, it did not change the risk of immediate infusion reactions.
  • Risk of DHR was: 5.3% at 2-11 months, 33% at 12-23 months, and 50% at ≥24 months (P<0.002). Patients were 21.4 (95% confidence interval [CI], 2.9-154.1; P=0.002) times more likely to have a DHR when a ≥12-month time interval elapsed. Similarly, patients with prior reactions were 27.5 (95% CI, 2.3-331.5; P=0.009) times more likely to have a DHR, after adjusting for immunosuppressives, number of previous infusions, gender, and age.

Cheifetz et al (2003)3 evaluated the incidence and management of acute infusion reactions to REMICADE in a retrospective study of 165 patients with CD who had received a total of 479 REMICADE infusions.

  • Over the 2.5-year assessment period, 3 delayed infusion reactions (reactions >24 hours postinfusion) were observed.
  • All patients received only a single induction infusion of REMICADE for luminal CD.
  • One patient was retreated with REMICADE and subsequently developed a delayed infusion reaction that resolved without treatment.
  • Of the remaining 2 patients, 1 patient developed a DHR after the induction dose and was retreated without problems. The other patient experienced a DHR after the fourth REMICADE infusion, 8 weeks after the third infusion. Symptoms for both patients included jaw tightness, arthralgias, myalgias, and fever.
  • Additionally, another patient who experienced a DHR was referred to the center and was successfully retreated with a concomitant 1-week course of diphenydramine and acetaminophen.

Panaccione (2002)4 described the clinical course of 6 patients who experienced a delayed-type hypersensitivity reaction following a repeat infusion of REMICADE after a period of no REMICADE treatment.

  • The reactions occurred at a median of 28 weeks (range, 12-48 weeks) following the initial infusion of REMICADE (dose not reported).
  • All patients were treated with a 1-week course of corticosteroids to manage their symptoms.
  • Five of the 6 patients were retreated with REMICADE and were given a 3-day short course of corticosteroid prophylaxis, with the first dose given the day prior to the infusion. All 5 patients tolerated retreatment with REMICADE using this prophylactic regimen. In addition, patients were able to achieve a clinical response, lasting a median of 18 weeks (range, 6-30 weeks).
  • Of the 5 patients, 3 continued to receive REMICADE every 6-8 weeks under the cover of corticosteroid prophylaxis. Additionally, response/remission was maintained without any adverse events.


A literature search of Ovid MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 06 October 2021. Summarized in this response are retrospective studies that evaluated the incidence of DHR after the administration of REMICADE.


1 REMICADE (infliximab) [Prescribing Information]. Horsham, PA: Janssen Pharmaceuticals, Inc; https://imedicalknowledge.veevavault.com/ui/approved_viewer?token=7994-faa9e14b-9f63-4a89-bee0-a157cd9277bb .
2 Bonner G, Cruz-Correa M. Delayed hypersensitivity reactions following REMICADE infusion. Analysis of Risk Factors. Abstract 105573 presented at: Digestive Disease Week; May 16-19, 2004; New Orleans, LA.
3 Cheifetz A,  Smedley M,  Martin S, et al. The incidence and management of infusion reactions to REMICADE: A large center experience. Am J Gastroenterol. 2003;98:1315-1324.
4 Panaccione R. Overcoming “delayed-type hypersensitivity reactions” in patients receiving repeated doses of REMICADE: A report of 5 cases. Digestive Disease Week; May 19-22, 2002; San Francisco, CA.