Review and Expert Opinion on Prevention and Treatment of Infliximab-related Infusion Reactions

L.L.A. Lecluse; G. Piskin; J.R. Mekkes; J.D. Bos; M.A. de Rie

Disclosures

The British Journal of Dermatology. 2008;159(3):527-536. 

In This Article

Abstract and Introduction

Infliximab (Remicade®; Schering-Plough, Kenilworth, NJ, U.S.A.) is a chimeric monoclonal antibody that acts as a tumour necrosis factor-α inhibitor. Infliximab is registered for the treatment of rheumatoid arthritis, psoriatic arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis and plaque-type psoriasis. Like other foreign protein-derived agents, infliximab may lead to infusion reactions during and after infusion. Infusion reactions occur in 3-22% of patients with psoriasis treated with infliximab. Most of these reactions are mild or moderate and only few are severe. Nevertheless, they may lead to discontinuation of treatment. As infliximab for psoriasis is prescribed as a last resort and is in most cases very effective, discontinuation of treatment is undesirable. With proper care and prevention of the infusion reactions the need to discontinue treatment with infliximab can be diminished. The objective of this article is to present a guideline for the management of infliximab-related infusion reactions, based on the best available evidence. This guideline can be used in patients with psoriasis as well as in dermatology patients receiving infliximab for off-label indications such as hidradenitis suppurativa or pyoderma gangrenosum.

Infliximab (Remicade®; Schering-Plough, Kenilworth, NJ, U.S.A.) is a chimeric monoclonal antibody (75% human, 25% mouse) that acts as a tumour necrosis factor-α inhibitor. Infliximab is registered for treatment of rheumatoid arthritis (RA), psoriatic arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis and plaque-type psoriasis. In dermatology it is also used for off-label indications such as hidradenitis suppurativa and pyoderma gangrenosum among others.[1] Infliximab has proven to be very effective in the treatment of moderate to severe chronic plaque-type psoriasis. In several randomized controlled trials (RCTs) around 80% of patients showed an improvement of at least 75% in the Psoriasis Area and Severity Index (PASI 75) after 10weeks of treatment, and more than half of the patients even showed an improvement of more than 90% (PASI 90).[2,3,4]

During and after the intravenous administration of infliximab infusion reactions can occur, comparable with what happens when using other foreign protein-derived treatments. Infusion reactions during the infusion or in the first 24h afterwards are defined as acute reactions.[5,6] The majority occurs during or in the first 2h after the infusion. Symptoms include 'flushing', chest tightness, dizziness, shortness of breath, headache, hypo/hypertension, nausea, sweating, rise in temperature and (other) symptoms of anaphylaxis, like urticaria and bronchospasms.[3,5,7] Delayed reactions are reactions that occur between 24h and 14days after an infusion, the majority occurring after 5-7days.[5] In most cases symptoms include arthralgia, myalgia, influenza-like symptoms, headache, tiredness and 'rash' or urticaria.[4,5,8]

Infusion reactions appear in 3-22% of patients with psoriasis who are treated with infliximab;[7] in placebo arms this is approximately 0-2%.[3,4] The reactions can be subdivided into mild, moderate or severe reactions. Most reactions are mild or moderate and only few are severe.[3] The severity of infusion reactions is assigned by the physician based on the patient's signs and symptoms; however, they do not always fit neatly into the definition of mild, moderate or severe reactions.[6] Mild reactions can be defined as reactions that are self-limiting and resolve spontaneously after temporary cessation of the infusion or reduction of the infusion speed. Moderate reactions are those that require closer attention and an extended observation period and often discontinuation of the infusion. Serious reactions involve respiratory symptoms or a symptomatic blood pressure drop and need for close monitoring, often for 24h and occasionally requiring hospital admission.[9] A severe infusion reaction can be anaphylactic or anaphylactoid and should be treated as such (Fig. 1). In these cases infliximab should be stopped immediately.[5]

Flowchart for the management of infliximab infusion reactions. aThe infusion rates advised are based on the dose of infliximab (xmg) being dissolved in 250mL of 0·9% saline. BP, blood pressure; i.m., intramuscular.

In an RCT with infliximab 1% of patients with psoriasis developed a severe infusion reaction; similar percentages are seen in patients who are treated with infliximab for other indications.[4] Also the symptoms[3,4] and mechanisms of infusion reactions are thought to be comparable for all patients treated with infliximab, independent of indication for use. The exact mechanisms of infusion reaction development, however, are not yet clear, although several factors and possible mechanisms have been suggested. These include anaphylactic/anaphylactoid reactions, serum sickness-like reactions and development of IgG antibodies against infliximab. These factors and mechanisms will be described in more detail.

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