Summary

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• In rheumatoid arthritis (RA), Crohn’s disease (CD) and psoriasis (Ps) clinical trials, re-administration of REMICADE after a period of no treatment resulted in a higher incidence of infusion reactions relative to regular maintenance treatment. In general, the benefit-risk of re-administration of REMICADE after a period of no-treatment, especially as a re-induction regimen given at weeks 0, 2 and 6, should be carefully considered. In the case where REMICADE maintenance therapy for Ps is interrupted, REMICADE should be reinitiated as a single dose followed by maintenance therapy.¹
• In a clinical trial of patients with moderate to severe Ps designed to assess the efficacy of long-term maintenance therapy versus re-treatment with an induction regimen of REMICADE following disease flare, 4% (8/219) of patients in the re-treatment induction therapy arm experienced serious infusion reactions versus <1% (1/222) in the maintenance therapy arm. Patients enrolled in this trial did not receive any concomitant immunosuppressant therapy. In this study, the majority of serious infusion reactions occurred during the second infusion at Week 2. Symptoms included, but were not limited to, dyspnea, urticaria, facial edema, and hypotension. In all cases, REMICADE treatment was discontinued and/or other treatment instituted with complete resolution of signs and symptoms.¹
• In Ps studies, approximately 1% of REMICADE-treated patients experienced a possible delayed hypersensitivity reaction, generally reported as serum sickness or a combination of arthralgia and/or myalgia with fever and/or rash. These reactions generally occurred within 2 weeks after repeat infusion.¹
• Clinical data pertaining to the reinduction of infliximab therapy after a drug-free period in patients with RA is available in the published literature.^2,3

CLINICAL DATA

ATTRACT

Buch et al (2004)² conducted an independent study of 17 patients at a site in Leeds who completed the ATTRACT study and continued treatment with methotrexate (MTX) alone.

The ATTRACT trial was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the safety and efficacy of infliximab in 428 patients with active RA despite treatment with MTX.^4-6

Study Design/Methods

• All patients in ATTRACT received treatment with MTX and were randomized to 1 of 5 treatment groups: infliximab 3 mg/kg or infliximab 10 mg/kg infused every 4 or 8 weeks, or placebo infused every 4 weeks.
• Patients initially received infliximab infusions at weeks 0, 2, and 6, and maintenance treatment based on their randomization schedule.
• Of the 428 patients who were randomized, 259 patients continued into the second year of treatment, and 216 patients completed the second year of therapy.

Results

• All patients relapsed and were restarted on infliximab 3 mg/kg at weeks 0, 2, and 6 and then every 8 weeks thereafter.
• Mean time to flare ranged between 13.5 and 15 weeks among the 5 treatment groups.
• Fifteen patients received infliximab and 2 patients received other treatments. Of the infliximab-treated patients, ACR-N response at 9 months after reinduction was comparable to previous response in 12 patients, worse in 2 patients, and not reported in 1 patient who stopped treatment due to an attempted pregnancy. No infusion reactions or adverse events were observed.

Case Report

Toki et al (2008)³ described a case of 65-year-old female patient with RA who discontinued infliximab due to an infusion reaction after a drug-free interval of more than 1 year.

• Following an inadequate response to prednisolone and MTX, infliximab 3 mg/kg was added at weeks 0, 2, and 6, and every 8 weeks thereafter.
• Despite a significant decrease in disease activity, infliximab was discontinued due to the occurrence of interstitial pneumonitis after 6 infusions.
• Following her recovery, she was treated with MTX and etanercept.
• infliximab was readministered after a 14 month interval due to a lack of efficacy with etanercept. Measures taken for infusion reaction prophylaxis included adjusting the infusion rate and premedication with a combination of H1 and H2 receptor antagonists and hydrocortisone.
• The first infusion was uneventful with a subsequent decrease in swelling and tenderness. However, infliximab was discontinued after the patient developed severe urticaria and pruritus 60 minutes after the start of the second infusion. A complete resolution of infusion-related symptoms was noted after treatment with intravenous diphenhydramine 5 mg with lactated Ringer's solution.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 24 July 2024.