Side Effects of Injected or Infused Biologic Drugs

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Biologic drugs, which have been marketed for certain types of inflammatory arthritis since 1998, are administered either by infusion or self-injection. Side effects, which can occur with these drugs, are referred to as infusion reactions or injection site reactions. Sounds scary, doesn't it? But, you should know that the reactions are rarely severe and often pass without any intervention.

Common Infusion Side Effects

Common problems related to infusion reactions may include headache, nausea, urticaria (hives), pruritus (itching), rash, flushing, fever, chills, tachycardia (rapid heartbeat), and dyspnea (difficulty breathing).

While it is rare, severe reactions or anaphylactic reactions can occur. In such cases, tightness of the chest, bronchospasm, hypotension (low blood pressure), diaphoresis (sweating), or anaphylaxis (a severe allergic reaction to a foreign protein that results from previous exposure to it) may occur. If a severe reaction develops, the biologic treatment should be stopped immediately and emergency care provided. In some cases, pre-medication with acetaminophen, an antihistamine, and a short-acting corticosteroid may help to prevent infusion reactions.

According to the authors of Rheumatoid Arthritis: Early Diagnosis and Treatment, clinical trial data revealed that while about 20% of patients treated with Remicade (infliximab) had an infusion reaction, less than 1% of Remicade-treated patients experienced a severe infusion reaction and only 2.5% of infusion reactions among Remicade-treated patients led to discontinuation of the drug. Typically, infusion reactions associated with Remicade occur during the infusion or within two hours after the infusion is completed.

Let's consider what the prescribing information for other biologic drugs revealed, keeping in mind that different clinical trials cannot be compared (e.g., Remicade trial results cannot be compared to Simponi trial results) and clinical trial data may not match up to the actual frequency in real practice.

  • Simponi Aria: In the controlled phase of Trial 1 (through week 24), 1.1% of Simponi Aria infusions were associated with an infusion reaction compared with 0.2% of infusions in the control group. Rash was the most common infusion reaction. No serious infusion reactions were reported.
  • Orencia (Abatacept): Orencia studies III, IV, and V revealed that acute infusion reactions were more common among Orencia-treated patients compared to placebo (9% vs. 6% respectively). The most frequently reported events were dizziness, headache, and hypotension (1-2%). Fewer than 1% of Orencia-treated patients discontinued use of the drug due to an acute infusion reaction. Anaphylaxis occurred in less than 0.1% of patients treated with Orencia.
  • Actemra (Tocilizumb): In the 24-week controlled clinical studies, acute infusion reaction occurred in 7-8% of patients, depending on which of the two dosages of Actemra was used, compared to 5% in the placebo group. The most frequent event during the infusion was hypertension (1%). The most frequent events within 24 hours of the infusion were headache (1%) and skin reactions (1%). The events did not cause discontinuation or limitation of treatment.
  • Rituxan (Rituximab): Administration of Rituxan can result in serious, including fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion.

In the Rituxan RA pooled placebo-controlled studies, acute infusion reactions (fever, chills, rigors, pruritus, urticaria or rash, angioedema, sneezing, throat irritation, cough, or bronchospasm, with or without associated hypotension or hypertension) were experienced by 27% of Rituxan-treated patients following their first infusion, compared to 19% of the placebo group.

The incidence of the acute infusion reactions following the second infusion of Rituxan or placebo decreased to 9% and 11%, respectively. Serious acute infusion reactions were experienced by <1% of patients in either treatment group. Dose modification was needed in 10% of Rituxan-treated patients vs. 2% of the placebo group.

Common Injection Side Effects

With biologic drugs that are administered subcutaneously, injection site reactions can occur but typically no treatment is required and discontinuation of the drug is not necessary.

Researchers also have looked at clinical trial data to assess the frequency of injection site reactions. While it offers some idea, remember, different clinical trials cannot be compared and the clinical trial data is not necessarily indicative of what occurs in a real practice.

  • Enbrel (Etanercept): In placebo-controlled trials for rheumatologic conditions, approximately 37% of patients treated with Enbrel developed injection site reactions. All injection site reactions were described as mild to moderate (erythema, itching, pain, swelling, bleeding, bruising) and generally did not lead to drug discontinuation. Injection site reactions, mostly lasting 3 to 5 days, generally occurred in the first month and subsequently decreased in frequency.
  • Humira (Adalimumab): In placebo-controlled trials, 20% of patients treated with Humira developed injection site reactions (erythema, itching, hemorrhage, pain or swelling), compared to 14% of patients receiving placebo. Most injection site reactions were described as mild and generally did not necessitate drug discontinuation.
  • Simponi (Golimumab): In the controlled Phase II/III trials, 3.4% of Simponi-treated patients had injection site reactions compared with 1.5% in the control group. Most of the injection site reactions were mild and moderate, with the most frequent manifestation being erythema.
  • Cimzia (Certolizumab Pegol): There was a mention of the possibility of injection site reaction with Cimzia in the prescribing information, described as rare, but no extensive details were provided.
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Article Sources
  • Cush, Weinblatt, Kavanaugh. Rheumatoid Arthritis: Early Treatment and Diagnosis. Third Edition. Professional Communications, Inc. 2010.