STOCKHOLM, Sweden—Treatment-limiting infusion reactions to infliximab (Remicade®, Centocor Inc) are significantly less likely in rheumatoid arthritis (RA) patients who are also taking low-dose glucocorticoids (GCs). Furthermore, such treatment-limiting reactions "have become significantly less common during the past 5 years," perhaps because clinicians are better at diagnosing the first signs of infusion reactions and either reducing the infusion rate or taking other preventive measures.

Jenny Augustsson, MD, reported in Annals of the Rheumatic Diseases,¹  "The use of daily low-dose glucocorticoids is associated with a lower risk for treatment-limiting infusion reactions to infliximab."

NNT to prevent a treatment-limiting infusion reaction is 25

Dr. Augustsson and colleagues at Karolinska University Hospital in Stockholm, Sweden, identified a registry-based cohort of 43 patients with immediate-type infusion reactions. They compared these patients with the entire cohort (N = 639) and with a nested matched control group (n = 43).

The investigators compared use of oral GCs, health-assessment questionnaire, 28-joint count-based disease activity score, duration of disease, and number of failed disease-modifying antirheumatic drugs (DMARDs). The rate of infusion reactions in the cohort was 4.6% in patients taking low-dose GCs compared with 8.6% in patients without GC treatment (P = .057). The rate of infusion reactions in the nested matched control group was 35% in GC-treated patients compared with 64% in nonGC-treated patients (P = .017).

Kaplan-Meier analysis showed that the use of low-dose GCs was associated with a significantly lower risk for treatment-limiting infusion reactions (P = .04). The proportion of infusions associated with treatment-limiting reactions decreased from 5.92% in the year 2000 to 1.14% in 2003. The researchers suggest that this might be partly due to "increased experience among physicians choosing the right pharmacological treatment for each patient," partly due to staff now experienced in recognizing the early signs of an infusion reaction in time to lower the infusion rate before the need for stopping treatment, or partly due to "subtle changes in the manufacturing process of the drug that might have decreased the risk of immunological reactions."

Daily low-dose GCs appeared to provide additional protection. "We demonstrated a clear protective effect of daily low-dose oral prednisolone which indicates a reduction in the risk for an infusion reaction by about half," Dr. Augustsson said. The number-needed-to-treat (NNT) with low-dose GC for a 5-year period to prevent one treatment-limiting infusion was 25. The researchers point out that while many physicians "tend to decrease or stop treatment with glucocorticoids, due to a fear of long-term side effects, when the patient receives a positive response to DMARD treatment," low-dose prednisolone also has been shown to slow radiographic progression in early RA.

The mechanism for the protective effect against infliximab infusion reactions is unknown but might involve human antichimeric antibodies, which tend to be lower in patients who have taken GCs. The authors suggest that another possible explanation for the reduction in infliximab infusion reactions might be that patients not taking GCs might have higher inflammatory burdens and be more susceptible to adverse events, or that "chronic immunological activity itself may predispose to immunological adverse events."

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