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Infliximab Administration Reactions– Studies of Infusion and Hypersensitivity Reactions

Administration-related reactions, including infusion reactions and hypersensitivity reactions, in patients treated with infliximab have been reported in published postmarketing studies. A summary of these published reports is provided in this section. These reports are presented in chronological order with the most recent date of publication first. References to additional publications discussing infusion reactions and infliximab are provided here for your convenience. ^{11582,  11583,  11584,  11585,  11586,  11587,  11509,  11589,  11590,  11591,  8081,  11708} 

The inclusion of postmarketing reports in this section should not be read to rule out the existence of other reports of administration-related reactions, published or otherwise.

Studies of Infusion Reactions and Hypersensitivity Reactions

Infusion reactions and hypersensitivity reactions with infliximab have been reported in published postmarketing reports.

Domenech, et al., 2010 (Study of Infusion Reactions After Infliximab Reintroduction in Inflammatory Bowel Disease)

Domenech, et al., conducted a retrospective review using clinic data and identified all patients who had initially had a complete response with a 3-dose regimen of infliximab but then had a relapse and required additional doses ≥4 months later. This timing was assessed to determine if restarting infliximab after a hiatus or gap in treatment was associated with a higher incidence of acute infusion reactions or a secondary loss of response. ¹²⁴¹⁶ 

All patients were treated with 5 mg/kg infliximab with the same initial 3-infusion induction scheme. Patients in the Continuous group (n=47) were given scheduled maintenance treatment, and patients in the Reintroduced group (n=29) received an induction regimen and at reintroduction followed scheduled infusions. The time since last infusion in the Reintroduction group ranged from 4 months to 47 months, with a median 13 months since last infusion. Eighty-one percent of patients in the Continuous group and 63% of patients in the Reintroduced group were premedicated with IV hydrocortisone from the first infliximab infusion, but this difference was not statistically significant (P=0.07). Fifty-six percent of patients in the Reintroduced group and 70% in the Continuous group had both concomitant immunomodulators and premedication with hydrocortisone, 27% in the Reintroduced group and 9% in the Continuous group had only concomitant immunomodulators, 7% in the Reintroduced group and 11% in the Continuous group had only premedication with hydrocortisone, and 10% of patients in both groups had neither immunomodulators or hydrocortisone. From the year 2004 on, all patients were pretreated with 200 mg of IV hydrocortisone before every infliximab infusion.

The immunogenic adverse events that occurred in the patients reintroduced to infliximab therapy were compared to the adverse events in a group of patients treated with continuous infliximab maintenance therapy. Thirteen patients (17%) developed acute infusion reactions, 5 in the Reintroduced treatment group (17%) and 8 in the Continuous treatment group (17%), and a delayed hypersensitivity reaction occurred in 1 patient in the Continuous treatment group. The use of concomitant immunomodulators and/or pretreatment with hydrocortisone was inversely associated with acute infusion reaction.¹²⁴¹⁶  In all clinical studies submitted for registration, approximately 20% of infliximab-treated patients experienced an infusion reaction compared to approximately 10% of patients receiving placebo.³²⁰⁴ 

Lees, et al., 2009 (Study in Inflammatory Bowel Disease)

Lees, et al., conducted a retrospective review of case records for 202 patients treated with infliximab at 2 hospitals in Edinburgh between 1999 and 2007.¹¹⁸²⁸  The 202 patients, who collectively received a total of 718 infusions, included 157 with Crohn’s disease (CD), 42 with ulcerative colitis, and 3 with another disease. Median follow-up was 2.4 years and ranged from 1 to 4.9 years for a total of 620 patient-years of follow-up. The median age at the onset of infliximab therapy was 30.8 years; 13.5% of patients were under the age of 18 at the time of first treatment. Thirty of the 157 patients with CD were started on another anti-TNF drug following discontinuation of infliximab.

Twenty acute infusion reactions occurred in 19 of 202 patients (9.4%). In 11 of these cases (55%), the infusion was discontinued. Four infusion reactions were serious, including 3 cases requiring hospital admission and 1 case of anaphylaxis requiring adrenaline. One patient developed a serum sickness-like reaction 4 days post infusion reaction. Two infusion reactions occurred after first infliximab infusion; for the remainder, median time since last infusion was 63.0 days (interquartile range [IQR] 37.0-156.5). The median number of prior infusions was 3.5 (IQR 2.0-6.5). Of 17 cases where details of concomitant medication were available, infusion reactions occurred in the presence of concomitant immunosuppressants in 16 of 17 cases (concomitant medication details were unavailable in 3 nonserious cases). All patients received preinfusion hydrocortisone, and 2 patients also received preinfusion chlorpheniramine. Five patients were successfully reinfused with infliximab, 1 with preinfusion chlorpheniramine. One patient experienced a mild infusion reaction upon reinfusion.¹¹⁸²⁸  In all clinical studies submitted for registration, approximately 20% of infliximab-treated patients experienced an infusion reaction compared to approximately 10% of patients receiving placebo.³²⁰⁴ 

Lichtenstein, et al., 2009 (Inflammatory Bowel Disease-Subgroup Analyses Across Four Phase 3 Randomized Trials)

The safety and efficacy of concomitant immunomodulator and infliximab therapy was evaluated in an integrated analysis of data from 4 Phase 3 clinical trials of infliximab, including ACCENT I and ACCENT II (luminal and fistulizing Crohn’s disease trials (including all randomized patients including induction, maintenance, and crossover) and ACT 1 and ACT 2 (ulcerative colitis trials).¹²⁴¹³  Individual trial descriptions and infusion reaction data can be found in  Infliximab and the Risk of Administration Reactions in Patients With Crohn’s Disease - Clinical Trial Information and  Infliximab and the Risk of Administration Reactions in Patients With Ulcerative Colitis - Clinical Trial Information. Clinical trial data from 1383 placebo or infliximab-treated IBD patients were pooled and analyzed to evaluate impact of concomitant immunomodulator use and compare certain safety events, including infusion reactions and immunogenicity.

Of the infliximab-treated patients who received concomitant immunomodulators, 12.5% (47⁄376) experienced infusion reactions, while 22.0% (139⁄631) of infliximab-treated patients without immunomodulators experienced an infusion reaction. When these data were evaluated based on the number of infusions received, similar trends were observed. Infusion reactions occurred in 2.6% (61⁄2320) of infusions in infliximab-treated patients who received concomitant immunomodulators compared with 5.0% (199⁄3987) of infusions in patients who did not receive immunomodulators. Most infusion reactions were mild-to-moderate in nature and serious infusion reactions occurred in less than 0.1% (1⁄2320) of infusions in infliximab treated patients who received concomitant immunomodulators and 0.1% (4⁄3987) of infusions in patients did not receive immunomodulators.¹²⁴¹³ 

Approximately 20% of REMICADE-treated patients in all clinical studies experienced an infusion reaction compared to approximately 10% of placebo-treated patients. Serious infusion reactions occurred in <1% of patients and included anaphylaxis, convulsions, erythematous rash and hypotension. Approximately 3% of patients discontinued REMICADE because of infusion reactions, and all patients recovered with treatment and/or discontinuation of the infusion.³²⁰⁴ 

Immunogenicity data from this study can be found in  Infliximab Administration Reactions - Studies of Immunogenicity.

Russo, et al., 2009 (Study in Ulcerative Colitis)

In conducting a retrospective study of infliximab in patients with ulcerative colitis, Russo, et al., compiled data via web-based questionnaire directed at gastroenterologists in the United Kingdom.¹¹⁸⁵⁸  Results from 38 patients at 6 hospitals were analyzed. All patients were on the recommended induction and maintenance regimen of infliximab 5 mg/kg at Weeks 0, 2, and 6, followed by infusions every 8 weeks.

A total of 352 infusions were administered. One patient experienced a mild infusion reaction, and another experienced a mild delayed hypersensitivity reaction. Details of these reactions were not provided, but neither patient discontinued treatment.

Caspersen, et al., 2008 (Study in Inflammatory Bowel Disease)

In a study designed to assess infliximab treatment in Danish patients with inflammatory bowel disease (IBD), Caspersen, et al., reviewed charts of 651 patients treated for IBD between 1999 and 2005.¹²⁰⁶³  A total of 3351 infusions were administered in this cohort (dosing regimen not specified); the median number of infusions was 3 (range 1 to 42). A number of patients were taking other medications at some point during their infliximab treatment; 447 were receiving azathioprine (AZA), and 64 were receiving methotrexate (MTX). (It was not specified whether any patients were taking both.)

A total of 111 patients experienced 146 infusion reactions collectively, the most common reactions being anaphylaxis, headache, nausea, and itching rash. Symptoms were considered anaphylactic if 3 or more of the following symptoms were present: headache, nausea, rash, flushing, chest pain, dyspnea, tachycardia, bradycardia, angioedema, urticaria, itching, hypotension, or hypertension. The symptoms of flushing and chest pain, flushing and dyspnea, or urticaria and dyspnea also were considered anaphylactic. Infliximab was discontinued in 24 of the patients with infusion reactions.

De Oliveira, et al., 2008 (Study in Psoriasis)

De Oliveira, et al., reported on their experience with infliximab in 19 patients with long-standing moderate-to-severe psoriasis that was refractory to other systemic treatments.¹¹⁸⁶⁰  All patients were treated with infliximab 5 mg/kg at Weeks 0, 2, and 6, and then every 8 weeks. No concomitant medications were administered. Four patients experienced infusion reactions within 1 hour of infusion, with a range of symptoms that included flushed skin, dyspnea, irregular heart rates, and chest tightness. Infliximab was discontinued in 2 of these patients, 1 after 2 infusions and 1 after 4 infusions. Twelve patients experienced delayed infusion reactions such as influenza-like symptoms, joint pain, vomiting and diarrhea, and uterine bleeding. It was not clear whether any of these patients discontinued treatment with infliximab.

Moss, et al., 2008 (Study in Crohn’s Disease)

Moss, et al., conducted a retrospective study to evaluate long-term outcomes in patients with CD who experienced infusion reactions to infliximab.¹¹⁸⁶¹  They reviewed the charts of 287 patients who received infliximab at a Boston medical center from 2000 to 2006 and were followed for at least 1 year. Over this time-frame, infliximab was administered either as “on-demand” or on a “maintenance” basis. The patients had received 2715 infusions, collectively, with 162 infusion reactions documented across 51 patients. Among the 51 patients who developed at least one infusion reaction, 31 experienced acute reactions, and 20 experienced delayed reactions. Reactions were mild in 15 patients, moderate in 34 patients, and severe in 2 patients. One patient required epinephrine for an anaphylactic reaction, and another developed severe bronchospasm with hypoxia. The most common infusion reactions were urticaria/rash and myalgia/arthralgia, followed by cardiopulmonary symptoms such as chest pain and dyspnea. Of the patients who experienced a primary response to infliximab, 67% discontinued treatment. Discontinuation numbers were not provided for the entire study population.

Takeuchi, et al., 2008 (Study in Rheumatoid Arthritis)

Takeuchi, et al. (2008), conducted a postmarketing surveillance study in 5000 Japanese rheumatoid arthritis (RA) patients treated with infliximab.⁸⁰⁹⁵  Patients treated with 3 mg/kg infliximab at Weeks 0, 2 and 6, and every 8 weeks thereafter, between July 2003 and December 2004, were enrolled, and each patient was followed for 6 months. Infusion reactions occurred in 484 (9.7%) of the 5000 patients. In all clinical studies submitted for registration, approximately 20% of infliximab-treated patients experienced an infusion reaction compared to approximately 10% of patients receiving placebo.³²⁰⁴  In this study, the majority of infusion reactions were not serious and included fever (2.4%), hot flashes (1.6%), and rash (1.5%). Serious infusion reactions occurred in 24 patients (0.5%), with decrease in blood pressure (9 cases) and anaphylactic/anaphylactoid symptoms (9 cases) occurring most frequently. Demographic analysis showed that serious infusion reactions were more common in patients that previously participated in an infliximab clinical trial or in patients using >8 mg/week of MTX (P<0.001).

Figueiredo, et al., 2008 (Study in Rheumatoid Arthritis)

Figueiredo, et al. (2008), studied 152 RA patients treated with infliximab at Montpellier Teaching Hospital between 2000 and 2003.⁸⁰⁹⁶  Thirty-five patients (23%) experienced an infusion reaction. In all clinical studies submitted for registration, approximately 20% of infliximab-treated patients experienced an infusion reaction compared to approximately 10% of patients receiving placebo.³²⁰⁴  In this study, infusion reactions were controlled by reducing the infusion rate, discontinuing the infusion, or through the use of antihistamines and steroids. The infusion reactions, which were generally mild and transient, occurred most frequently during the third infusion. Ten patients (6.6%) discontinued treatment because of an infusion reaction. Patients that developed an infusion reaction had more frequently a history of allergy (P<0.001).

de Ridder, et al., 2008 (Study in Pediatric Crohn’s Disease)

In a retrospective study designed to evaluate duration of efficacy of infliximab 5 mg/kg in pediatric patients with Crohn’s disease (CD) in the Netherlands, records of 66 patients with fistulizing or severe luminal CD who initially responded to infliximab were reviewed. Eight of 66 patients experienced an immediate allergic reaction during infusion with infliximab. Symptoms were resolved with intravenous corticosteroids and antihistamines in 7 patients. The eighth patient also required epinephrine; treatment with infliximab was discontinued. The reaction in this patient was preceded by a 9-year, infliximab-free treatment regimen. No prophylactic medications were administered prior to this infusion. Two other patients discontinued treatment due to allergic reactions: 1 discontinued after the fourth infusion, and 1 discontinued after the 20th infusion.¹¹⁷²¹ 

Voulgari, et al., 2008 (Study in Psoriatic Arthritis)

Voulgari, et al., conducted a prospective, uncontrolled, open-label, 3-year study of 32 patients with psoriatic arthritis (PsA) that was refractory to at least 2 disease-modifying antirheumatic drugs. Participants were drawn from a cohort of 221 patients with PsA identified in an epidemiologic study by the same authors. Infliximab 5 mg/kg was administered at Weeks 0, 2, and 6, then every 8 weeks. Five patients experienced immediate hypersensitivity reactions and discontinued treatment. No additional details on the infusion reactions were provided.¹¹⁷²⁶ 

Kristensen, et al., 2008 (Study in Psoriatic Arthritis)

In an analysis of efficacy and safety data regarding TNF-α inhibitors in clinical practices in southern Sweden, Kristensen, et al., reviewed data on 261 patients with PsA who were being treated with TNF-α inhibitors for the first time. Eligible patients were those who exhibited high disease activity and/or unacceptable steroid use and were naive to biologic therapy. The TNF-α inhibitors were administered as add-on therapy. Those patients receiving infliximab 3 mg/kg (n=114) were infused at Weeks 0, 2, and 6, and then every 8 weeks. Depending on response, dosage and frequency could be increased to as much as 500 mg every 4 or 8 weeks. The average dose at 6 months was 5 mg/kg every 8 weeks. Two of the 114 infliximab patients experienced severe infusion reactions. No additional details about these patients were provided in the published study.¹¹⁷²⁸ 

Cheung, et al., 2008 (Study in Ankylosing Spondylitis)

Cheung, et al., reported 16 patients (of 27) that had one or more minor, nonserious, adverse events, including 3 patients with infusion reactions during treatment with infliximab.¹¹⁵⁹³  Twenty-seven patients were treated with infliximab 5 mg/kg at Weeks 0, 2, 6, and every 6 weeks thereafter. Most patients were males (78%) and had long-standing severe, established disease with a mean duration from onset of symptoms of 16.3 years (range 0.7-53.7). Infusion reactions for these patients were not further described.

Augustsson, et al., 2007 (Study in Rheumatoid Arthritis)

In a retrospective study, Augustsson, et al. (2007), identified 43 patients with immediate-type infusion reactions from the Stockholm TNF-α follow-up registry (STURE) out of a cohort of 672 patients treated with infliximab between 1999 and 2004.⁸⁰⁹⁷  The most common infusion reaction symptoms were shortness of breath/chest pressure, flushing, urticaria, and pruritus. In the cohort, 50% of the patients were on daily oral low-dose glucocorticoids, and 4.6% of patients on concurrent glucocorticoids had an infusion reaction as compared with 8.6% without glucocorticoid treatment. In all clinical studies submitted for registration, approximately 20% of infliximab-treated patients experienced an infusion reaction compared to approximately 10% of patients receiving placebo.³²⁰⁴ 

Chevillotte-Maillard, et al., 2005 (Study in Ankylosing Spondylitis and Rheumatoid Arthritis)

In an observational cohort study designed to evaluate the survival and safety of infliximab in older compared with younger patients, Chevillotte-Maillard, et al., report 6 allergic reaction in patients treated with infliximab at its recommended dosing.¹¹⁵⁹⁴  Older patients were defined as those starting infliximab treatment at 70 years of age or older, whereas younger patients were defined as those under the age of 70 at treatment start. In total, 83 patients — 60 with rheumatoid arthritis (RA) and 23 with ankylosing spondylitis (AS) — were followed for 1 year with the study end point defined as infliximab withdrawal. During follow-up, 30 patients (36.1%) withdrew infliximab treatment; of these, 6 patients withdrew treatment due to allergic reactions. However, there was no significant difference in the percentage of allergic reactions in older patients (9.1%) compared with younger patients (6.9%) (P=0.59).

Borrelli, et al., 2004 (Study in Pediatric Crohn’s Disease)

Borrelli, et al., conducted a trial of infliximab 5 mg/kg in 18 patients with severe pediatric CD and suboptimal response to conventional treatment. Four patients experienced infusion reactions with symptoms of dyspnea, cough, and shivers. Symptoms were alleviated by temporarily stopping infusion and then resuming at a lower rate. One patient also received diphenhydramine.¹¹⁷²³ 

Lamireau, et al., 2004 (Study in Pediatric Crohn’s Disease)

The French-Speaking Group for Pediatric Gastroenterology, Hepatology, and Nutrition review board conducted a retrospective study of pediatric patients (ages 3 to 17) with refractory CD who were treated with infliximab. Lamireau, et al., collected data on 88 patients; the mean value for each parameter was compared from Day 0 to Day 90. Dosage was 5 mg/kg except in 3 patients who received doses of 3.8 mg/kg, 4.5 mg/kg, and 7.3 mg/kg. A total of 450 infusions were administered; 13 patients experienced 16 infusion reactions collectively. Reactions associated with the first infusion included hypotension, headache, fatigue, and pruritus. Reactions stemming from subsequent infusions also included shivers, chest tightness, fever, flushing, nausea, and tachycardia. All reactions were considered limited but prompted one or more of the following: reduction in flow rate or administration of antihistamines, analgesics, or corticosteroids. Two patients exhibited symptoms suggestive of delayed hypersensitivity; 1 experienced polyarthralgia and fever 10 days after the third infusion, and the other experienced polyarthralgia and fever 14 days after the second and third infusions. Another patient developed a rash suggestive of lupus erythematosus after a second infusion without additional symptoms or presence of nuclear antibodies. The patient received 2 additional infusions over the next 6 months, and the rash disappeared spontaneously during that time period.¹¹⁷²⁴ 

Temekonidis, et al., 2003 (Study in Ankylosing Spondylitis)

In an open-label, 12-month study, Temekonidis, et al., reported 3 allergic reactions in 25 patients (24 male, 1 female) with severe refractory AS.¹¹⁵⁹⁵  In this study, patients were treated with infusions of infliximab 5 mg/kg at Weeks 0, 2, 6, and every 8 weeks thereafter. In addition to routine blood and urine analysis, serum samples were collected before each infusion to evaluate the autoantibody profile of each patient. Infliximab treatment was generally well tolerated. Adverse events (AEs) included mild allergic reactions (2 cases in 2 patients). Another patient experienced a severe immediate hypersensitivity reaction after the third dose of infliximab. This patient subsequently withdrew from the study. The authors reported that all AEs were resolved.

Baeten, et al., 2003 (Study in Ankylosing Spondylitis)

In a long-term, safety follow-up of 107 patients treated with infliximab for spondyloarthropathies, including AS, Baeten, et al., reported 1 infusion reaction to infliximab.¹¹⁵⁹⁶  Here, 107 patients were treated with infliximab for a total of 191.5 patient-years. Patients were monitored for all serious and/or treatment-related adverse events. A total of 20 adverse events were recorded during the follow-up period, including 1 infusion reaction. One 28-year-old female with active AS was treated with infliximab 5 mg/kg every 8 weeks after induction for a total of 28 weeks of treatment. This patient developed a mild infusion reaction that did not lead to discontinuation of infliximab therapy.

Cezard, et al., 2003 (Study in Pediatric Crohn’s Disease)

In a prospective study of 21 patients (age 13 to 17 years) with severe CD, Cezard, et al., administered infliximab 5 mg/kg, documenting 1 anaphylactic reaction during the second infusion. The patient was treated with corticosteroids, and the infusion was stopped. A total of 87 infusions (2 to 7 per patient) were administered during the course of this study.¹¹⁷²² 

Salvarani, et al., 2003 (Study in Psoriatic Arthritis)

In a 30-week, multicenter, prospective, open-pilot study evaluating the safety and efficacy of infliximab for treatment of psoriatic arthritis, Salvarani, et al., treated 16 patients whose disease was active despite treatment with methotrexate (MTX) for at least 6 months. Patients received infliximab 3 mg/kg at Weeks 0, 2, 6, 14, 22, and 30, while continuing on MTX. Four patients experienced infusion reactions; in 2 patients, these reactions were reported as severe. The severe reactions involved symptoms of dyspnea, bronchospasm, and hypotension. One reaction occurred after the first infusion; the other occurred after the fifth infusion. Symptoms were not resolved by slowing the infusion rate, and treatment was suspended. The 2 other patients experienced mild headache and nausea related to infusion of infliximab; their symptoms were resolved by slowing the infusion rate.¹¹⁷²⁷ 

Cheifetz, et al., 2003 (Study in Crohn’s Disease)

In a study designed to assess the incidence and management of infusion reactions to infliximab, Cheifetz, et al., conducted a retrospective study of 165 patients treated for Crohn’s disease (CD) at a New York clinical infusion center for a period spanning 2.5 years.¹¹⁸⁶²  Patients received 479 infusions of infliximab 5 mg/kg collectively; a total of 26 infusion reactions were documented. Fifteen infusion reactions were considered mild, 6 were considered moderate, and 5 were considered to be severe. All mild and moderate reactions resolved after treatment with acetaminophen, antihistamines, corticosteroids, and/or epinephrine. Infusions were successfully restarted at a slower rate in all but 1 case. Of the 5 patients who suffered severe infusion reactions, 2 were retreated without further reactions, 1 experienced a second severe reaction upon retreatment and discontinued infliximab, and the other 2 patients were discontinued without an attempt at retreatment.

Three delayed hypersensitivity reactions, defined as any infliximab-related event occurring >24 hours after infusion, were documented over the follow-up period of 2.5 years. All were in patients who had received only 1 induction dose for luminal CD. Symptoms resolved in all 3 patients without treatment. Another patient who developed a delayed hypersensitivity reaction was a referral from another clinic; the patient was retreated with infliximab along with concomitant administration of an antihistamine and acetaminophen.

Brockbank, et al., 2001 (Study in Psoriatic Arthritis)

In a study of 15 patients with psoriatic arthritis who had failed at least 2 disease-modifying antirheumatic drugs, infliximab 5 mg/kg was administered at Weeks 0, 2, 6, and then every 6 or 8 weeks depending on response. One patient experienced a severe allergic response to infliximab and was discontinued from the study. Additional details were not provided.¹¹⁷³⁰ 

Hyams, et al., 2000 (Study in Pediatric Crohn’s Disease)

In a chart review of 19 pediatric patients (ages 9 to 19 years) with active CD receiving a total of 60 infusions of infliximab 5 mg/kg, Hyams, et al., noted infusion reactions in 3 patients. One patient experienced dyspnea during the first infusion, which was stopped. The infusion was readministered uneventfully 1 week later with diphenhydramine pretreatment. A second patient experienced mild dyspnea and diffuse erythema during the second infusion. This infusion was also stopped and readministered uneventfully 1 week later with diphenhydramine pretreatment. In both cases the patients recovered from the reaction. A third patient experienced diffuse erythema, facial edema, and dyspnea during the second infusion, which was stopped. The patient recovered uneventfully, and treatment with infliximab was discontinued.¹¹⁷³¹ 

Case Reports of Infusion Reactions and Hypersensitivity Reactions

Infusion reactions and hypersensitivity reactions with infliximab have been reported in published case reports. The inclusion of case reports in this section should not be read to rule out the existence of other reports of administration-related reactions, published or otherwise.

Toki, et al., 2008 (Case Report in Rheumatoid Arthritis)

A 65-year-old woman with rheumatoid arthritis who had been on an infliximab hiatus for >1 year experienced an infusion reaction that led to discontinuation.¹¹⁸⁶³  Toki, et al., reported on this case in Japan of a woman who had previously been treated with infliximab 3 mg/kg at Weeks 0, 2, and 6, and then every 8 weeks. Infliximab was added to the previous regimen of methotrexate and corticosteroids. Infliximab was discontinued after 6 infusions due to development of interstitial pneumonia. After recovery, treatment was initiated with another anti-TNF therapy, which was later discontinued. Infliximab was restarted 14 months after its discontinuation. The patient was premedicated with antihistamines and hydrocortisone. During the second infusion of infliximab, the patient experienced severe urticaria and pruritus. The infusion was stopped, and symptoms were resolved with an intravenous antihistamine.

Margo, et al., 2008 (Case Report in Crohn’s Disease)

Margo, et al. (2008), reported 11 patients with active Crohn’s disease (CD) who experienced infusion reactions after episodic infliximab treatment, 4 acute and 7 delayed.⁸⁰⁹⁸  All patients started infliximab infusions (induction and episodic treatment), then after a variable period of time, began regular therapy. The median time of interruption between episodic and scheduled infliximab infusions was 35 months (5-66 months). All patients were taking azathioprine and received 75 mg prednisolone and clemastine before infliximab treatment. After the reaction, infliximab treatment was discontinued in all 11 patients. The recommended treatment regimen for infliximab administration for CD is 5 mg/kg given at Weeks 0, 2, and 6, followed by maintenance dosing every 8 weeks.³²⁰⁴ 

Hodosi, et al., 2007 (Case Report in Psoriatic Arthritis)

Hodosi, et al., reported a severe infusion reaction in a Hungarian patient with psoriatic arthritis being treated with infliximab (unspecified dose) after experiencing frequent relapses with conventional medication. Two hours following the fourth infusion, the patient experienced dyspnea and laryngeal spasm, both of which were resolved with administration of oral antihistamine. However, 2 days later, the patient broke out in generalized erythroderma. Infliximab was discontinued, corticosteroids were administered, and methotrexate (MTX) was reintroduced. Two months later, the erythroderma was still present despite increased dosing of MTX.¹¹⁷²⁹ 

Gamarra, et al., 2006 (Case Report in Crohn’s Disease)

In a recently published case report, Gamarra, et al. (2006), described 2 patients with inflammatory bowel disease (IBD) treated with infliximab who presented with similar systemic clinical features 7 to 9 days after infliximab treatment.⁶⁰¹⁹  The patients had no adverse reaction to their induction regimen and remained free from disease-related clinical symptoms for several months without further treatment. After the reappearance of symptoms, both patients were retreated with 1 dose of infliximab. The first patient presented with high fever, chills, malaise, severe joint and bone pains, skin rash, leukocytosis, and hematuria 9 days after the infusion; the second patient presented with severe chest wall pain, high fever, nausea, vomiting, shortness of breath, joint pain, and numbness after 7 days. The first patient’s symptoms resolved after several days’ treatment with antibiotics for an assumed sepsis, while the second patient’s symptoms improved over several hours with parenteral antihistamines and intravenous corticosteroids. Both patients had a full recovery after several days.

Of note, both patients were treated episodically for Crohn’s disease (CD), and both received initial infliximab doses at Weeks 0, 2, and 6, and then again only after their disease flared. The drug holiday was several months for the first patient and 9 months for the second patient. The recommended treatment regimen for infliximab administration for CD and ulcerative colitis is 5 mg/kg given at Weeks 0, 2, and 6, followed by maintenance dosing every 8 weeks.³²⁰⁴ 

Content on this page was last reviewed on January 30, 2009.

Content on this page was last changed on May 20, 2010.

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Rejón E, Giménez MD, Mayordomo L, et al. Therapeutic efficacy and safety of multiple intravenous infusions. Scan J Rheumatol . 2004;33(5):323-326.

11591.

Aybay C, Ozel S, Aybay C. Demonstration of specific antibodies against infliximab induced during treatment of a patient with ankylosing spondylitis. Rheum Int . 2006;26(5):473-480.

11593.

Cheung PP, Tymms KE, Wilson BJ, et al. Infliximab in severe active ankylosing spondylitis with spinal ankylosis. Intern Med J. 2008;38(6):396-401.

11594.

Chevillotte-Maillard H, Ornetti P, Mistrih R, et al. Survival and safety of treatment with infliximab in the elderly population. Rheumatology (Oxford). 2005;44(5):696-697.

11595.

Temekonidis TI, Alamanos Y, Nikas SN, et al. Infliximab therapy in patients with ankylosing spondylitis: an open label 12 month study. Ann Rheum Dis . 2003;62(12):1218-1220.

11596.

Baeten D, Kruithof E, Van den Bosch F, et al. Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease? Ann Rheum Dis. 2003;62(9):829-834.

11708.

Sakellariou GT, Chatzigiannis I. Long-term anti-TNFalpha therapy for ankylosing spondylitis in two patients with chronic HBV infection. Clin Rheumatol . 2007;26(6):950-952.

11721.

de Ridder L, Rings EH, Damen GM, et al. Infliximab dependency in pediatric Crohn’s disease: long-term follow-up of an unselected cohort. Inflamm Bowel Dis . 2008;14(3):353-358.

11722.

Cezard JP, Nouaili N, Talbotec C, et al. A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factors (remicade) in severe pediatric crohn disease. J Pediatr Gastroenterol Nutr . 2003;36(5):632-636.

11723.

Borrelli O, Bascietto C, Viola F, et al. Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease. Dig Liver Dis . 2004;36(5):342-347.

11724.

Lamireau T, Cézard JP, Dabadie A, et al. Efficacy and tolerance of infliximab in children and adolescents with Crohn’s disease. Inflamm Bowel Dis . 2004;10(6):745-750.

11726.

Voulgari PV, Venetsanopoulou AI, Exarchou SA, et al. Sustained clinical response and high infliximab survival in psoriatic arthritis patients: a 3-year long-term study. Semin Arthritis Rheum . 2008;37(5):293-298.

11727.

Salvarani C, Cantini F, Olivieri I, et al. Efficacy of infliximab in resistant psoriatic arthritis. Arthritis Rheum . 2003;49(4):541-545.

11728.

Kristensen LE, Gülfe A, Saxne T, et al. Efficacy and tolerability of anti-tumour necrosis factor therapy in psoriatic arthritis patients: results from the South Swedish Arthritis Treatment Group register. Ann Rheum Dis . 2008;67(3):364-369.

11729.

Hodosi B, Szepes E, Lengyel Z. Severe side effect of infliximab in a patient with therapy resistant psoriasis and psoriatic arthritis. J Eur Acad Dermatol Venereol . 2007;21(suppl 1):16.

11730.

Brockbank JE, Lapp V, Gladman DD. Infliximab therapy in 15 patients with psoriatic arthritis (PsA) [Abstract T92]. J Rheum . 2001;28(suppl 63):62.

11731.

Hyams JS, Markowitz J, Wyllie R. Use of infliximab in the treatment of Crohn’s disease in children and adolescents. J Pediatr . 2000;137(2):192-196.

11828.

Lees CW, Ali AI, Thompson AI, et al. The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up. Aliment Pharmacol Ther . 2009;29(3):286-297.

11858.

Russo EA, Harris AW, Campbell S, et al. Experience of maintenance infliximab therapy for refractory ulcerative colitis from six centres in England. Aliment Pharmacol Ther . 2009;29(3):308-314.

11860.

De Oliveira JP, Levy A, Morel P, et al. Efficacy of infliximab for severe recalcitrant psoriasis after 6 weeks of treatment. J Dermatol . 2008;35(9):575-580.

11861.

Moss AC, Fernandez-Becker N, Jo Kim K, et al. The impact of infliximab infusion reactions on long-term outcomes in patients with Crohn’s disease. Aliment Pharmacol Ther . 2008;28(2):221-227.

11862.

Cheifetz A, Smedley M, Martin S, et al. The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol . 2003;98(6):1315-1324.

11863.

Toki H, Momohara S, Tsukahara S, et al. Infusion reaction to infliximab in a patient with rheumatoid arthritis after discontinuation over 1 year and readministration. J Rheumatol . 2008;35(9):1896-1897.

12063.

Caspersen S, Elkjaer M, Riis L, et al; Danish Crohn Colitis Database. Infliximab for inflammatory bowel disease in Denmark 1999-2005: clinical outcome and follow-up evaluation of malignancy and mortality. Clin Gastroenterol Hepatol. 2008;6(11):1212–1217.

12413.

Lichtenstein GR, et al. Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment Pharmacol Ther 30, 210–226.

12416.

Domenech E., et al. Infliximab Reintroduction is Not Associated to a Higher Rate of Immune-related Adverse Effects in Patients With Inflammatory Bowel Disease Initially Treated With a Three-infusion Induction Regimen. J Clin Gastroenterol 2010;44:34–37.

Next Page: Infliximab Administration Reactions - Studies of Immunogenicity »

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3204

Remicade [prescribing information]. Malvern, PA: Centocor Ortho Biotech Inc.; November 2009.

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6019

Gamarra RM, McGraw SD, Drelichman VS, Maas LC. Serum sickness-like reactions in patients receiving intravenous infliximab. J Em Med. 2006;31(1):41-44.

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8081

Levälampi T, Korpela M, Vuolteenaho K, Moilanen E. Infliximab treatment in patients with rheumatoid arthritis and spondyloarthropathies in clinical practice: adverse events and other reasons for discontinuation of treatment. Scand J Rheumatol . 2008;37(1):6-12.

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Takeuchi T, Tatsuki Y, Nogami Y, et al. Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67(2):189-194.

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8096

Figueiredo IT, Morel J, Sany J, Combe B. Maintenance and tolerability of infliximab in a cohort of 152 patients with rheumatoid arthritis. Clin Exp Rheumatol. 2008;26(1):18-23.

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Augustsson J, Eksborg S, Ernestam S, Gullström E, van Vollenhoven R. Low-dose glucocorticoid therapy decreases risk for treatment limiting infusion reactions to infliximab in patients with rheumatoid arthritis. Ann Rheum Dis . 2007;66(11):1462-1466.

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8098

Margo F, Marques M, Santos CC. Episodic infliximab treatment induces infusion reactions [published online ahead of print April 8, 2008]. Inflamm Bowel Dis . 2008;14(11):1608-1610. doi: 10.1002/ibd.20476.

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pubmed-record

11509

Pérez-Guijo VC, Cravo AR, Castro Mdel C, Font P, Muñoz-Gomariz E, Collantes-Estevez E. Increased efficacy of infliximab associated with methotrexate in ankylosing spondylitis. Joint Bone Spine . 2007;74(3):254-258.

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11582

Marzo-Ortega H, McConagle D, Jarrett S, et al. Infliximab in combination with methotrexate in active ankylosing spondylitis: a clinical and imaging study. Ann Rheum Dis . 2005;64(11):1568-1575.

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pubmed-freefull

11583

Nikas SN, Alamanos Y, Voulgari PV, et al. Infliximab treatment in ankylosing spondylitis: an observational study. Ann Rheum Dis. 2005;64(6):940-942.

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11584

Gossec L, Le Henanff A, Breban M, et al. Continuation of treatment with infliximab in ankylosing spondylitis: 2-yr open follow-up. Rheumatology (Oxford) . 2006;45(7):859-862.

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11585

Maksymowych WP, Jhangri GS, Lambert RG, et al .Infliximab in ankylosing spondylitis: a prospective observational inception cohort analysis of efficacy and safety. J Rheumatol . 2002;29(5):959-965.

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pubmed-freefull

11586

Keeling S, Oswald A, Russell, AS, et al. Prospective observational analysis of the efficacy and safety of low-dose (3 mg/kg) infliximab in ankylosing spondylitis: 4-year followup. J Rheumatol . 2006;33(3):558-561.

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pubmed-freefull

11587

Buch MH, Bryer D, Lindsay S, et al. Shortening infusion times for infliximab administration. Rheumatology (Oxford). 2006;45(4):485-495.

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pubmed-freefull

11589

Li EK, Griffith JF, Lee VW, et al. Short-term efficacy of combination methotrexate and infliximab in patients with ankylosing spondylitis: a clinical and magnetic resonance imaging correlation. Rheumatology (Oxford). 2008;47(9):1358-1363.

Add to Library

pubmed-freefull

11590

Rejón E, Giménez MD, Mayordomo L, et al. Therapeutic efficacy and safety of multiple intravenous infusions. Scan J Rheumatol . 2004;33(5):323-326.

Add to Library

pubmed-freefull

11591

Aybay C, Ozel S, Aybay C. Demonstration of specific antibodies against infliximab induced during treatment of a patient with ankylosing spondylitis. Rheum Int . 2006;26(5):473-480.

Add to Library

pubmed-freefull

11593

Cheung PP, Tymms KE, Wilson BJ, et al. Infliximab in severe active ankylosing spondylitis with spinal ankylosis. Intern Med J. 2008;38(6):396-401.

Add to Library

pubmed-freefull

11594

Chevillotte-Maillard H, Ornetti P, Mistrih R, et al. Survival and safety of treatment with infliximab in the elderly population. Rheumatology (Oxford). 2005;44(5):696-697.

Add to Library

pubmed-freefull

11595

Temekonidis TI, Alamanos Y, Nikas SN, et al. Infliximab therapy in patients with ankylosing spondylitis: an open label 12 month study. Ann Rheum Dis . 2003;62(12):1218-1220.

Add to Library

pubmed-freefull

11596

Baeten D, Kruithof E, Van den Bosch F, et al. Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease? Ann Rheum Dis. 2003;62(9):829-834.

Add to Library

pubmed-freefull

11708

Sakellariou GT, Chatzigiannis I. Long-term anti-TNFalpha therapy for ankylosing spondylitis in two patients with chronic HBV infection. Clin Rheumatol . 2007;26(6):950-952.

Add to Library

pubmed-record

11721

de Ridder L, Rings EH, Damen GM, et al. Infliximab dependency in pediatric Crohn’s disease: long-term follow-up of an unselected cohort. Inflamm Bowel Dis . 2008;14(3):353-358.

Add to Library

pubmed-record

11722

Cezard JP, Nouaili N, Talbotec C, et al. A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factors (remicade) in severe pediatric crohn disease. J Pediatr Gastroenterol Nutr . 2003;36(5):632-636.

Add to Library

pubmed-record

11723

Borrelli O, Bascietto C, Viola F, et al. Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease. Dig Liver Dis . 2004;36(5):342-347.

Add to Library

pubmed-record

11724

Lamireau T, Cézard JP, Dabadie A, et al. Efficacy and tolerance of infliximab in children and adolescents with Crohn’s disease. Inflamm Bowel Dis . 2004;10(6):745-750.

Add to Library

pubmed-record

11726

Voulgari PV, Venetsanopoulou AI, Exarchou SA, et al. Sustained clinical response and high infliximab survival in psoriatic arthritis patients: a 3-year long-term study. Semin Arthritis Rheum . 2008;37(5):293-298.

Add to Library

pubmed-record

11727

Salvarani C, Cantini F, Olivieri I, et al. Efficacy of infliximab in resistant psoriatic arthritis. Arthritis Rheum . 2003;49(4):541-545.

Add to Library

pubmed-record

11728

Kristensen LE, Gülfe A, Saxne T, et al. Efficacy and tolerability of anti-tumour necrosis factor therapy in psoriatic arthritis patients: results from the South Swedish Arthritis Treatment Group register. Ann Rheum Dis . 2008;67(3):364-369.

Add to Library

pubmed-record

11729

Hodosi B, Szepes E, Lengyel Z. Severe side effect of infliximab in a patient with therapy resistant psoriasis and psoriatic arthritis. J Eur Acad Dermatol Venereol . 2007;21(suppl 1):16.

Add to Library

11730

Brockbank JE, Lapp V, Gladman DD. Infliximab therapy in 15 patients with psoriatic arthritis (PsA) [Abstract T92]. J Rheum . 2001;28(suppl 63):62.

Add to Library

11731

Hyams JS, Markowitz J, Wyllie R. Use of infliximab in the treatment of Crohn’s disease in children and adolescents. J Pediatr . 2000;137(2):192-196.

Add to Library

pubmed-record

11828

Lees CW, Ali AI, Thompson AI, et al. The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up. Aliment Pharmacol Ther . 2009;29(3):286-297.

Add to Library

pubmed-freefull

11858

Russo EA, Harris AW, Campbell S, et al. Experience of maintenance infliximab therapy for refractory ulcerative colitis from six centres in England. Aliment Pharmacol Ther . 2009;29(3):308-314.

Add to Library

pubmed-record

11860

De Oliveira JP, Levy A, Morel P, et al. Efficacy of infliximab for severe recalcitrant psoriasis after 6 weeks of treatment. J Dermatol . 2008;35(9):575-580.

Add to Library

pubmed-record

11861

Moss AC, Fernandez-Becker N, Jo Kim K, et al. The impact of infliximab infusion reactions on long-term outcomes in patients with Crohn’s disease. Aliment Pharmacol Ther . 2008;28(2):221-227.

Add to Library

pubmed-record

11862

Cheifetz A, Smedley M, Martin S, et al. The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol . 2003;98(6):1315-1324.

Add to Library

pubmed-record

11863

Toki H, Momohara S, Tsukahara S, et al. Infusion reaction to infliximab in a patient with rheumatoid arthritis after discontinuation over 1 year and readministration. J Rheumatol . 2008;35(9):1896-1897.

Add to Library

pubmed-record

12063

Caspersen S, Elkjaer M, Riis L, et al; Danish Crohn Colitis Database. Infliximab for inflammatory bowel disease in Denmark 1999-2005: clinical outcome and follow-up evaluation of malignancy and mortality. Clin Gastroenterol Hepatol. 2008;6(11):1212–1217.

Add to Library

pubmed-record

12413

Lichtenstein GR, et al. Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment Pharmacol Ther 30, 210–226.

Add to Library

12416

Domenech E., et al. Infliximab Reintroduction is Not Associated to a Higher Rate of Immune-related Adverse Effects in Patients With Inflammatory Bowel Disease Initially Treated With a Three-infusion Induction Regimen. J Clin Gastroenterol 2010;44:34–37.

Add to Library