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To the Editor:

We read with great interest the article by Wasserman and colleagues¹ on infusion related reactions to infliximab in patients with rheumatoid arthritis (RA). The authors did not assess any potential correlation between the frequency of infusion reactions and clinical response. However, some evidence of the relationship between infusion reactions and clinical response could be observed in the first 14 weeks. With regard to demand for escalating the infliximab dose from 3 mg/kg to 5 mg/kg at Week 14, the patients are separated into 2 groups, responders and nonresponders. The difference in the number of patients experiencing at least one infusion reaction during the first 14 weeks between the 2 groups may be significant.

The authors mention that there was no relationship between infusion reactions and prednisone dose. However, it is not reported if there was any difference in infusion reactions between patients with prednisone treatment and those without.

The results of study showed that pretreatment with antihistamine failed to reduce the frequency of infusion reactions in patients without previous reactions at infusions 3 and 4. However, other forms of pretreatment, such as steroids, may be more beneficial than diphenhydramine.

Although there are no reports of studies of infliximab treatment in patients with RA that indicate the association of infusion reactions with clinical response and standard steroid therapy, the trials of infliximab in patients with Crohn's disease (CD) have revealed some interesting results. In a prospective observational study of infliximab infusions in patients with CD², the duration of response to subsequent infusions decreased once an infusion reaction occurred. In the ACCENT I trial³, the incidence of infusion reactions was 23% among CD patients receiving steroids alone, compared with 32% of patients not taking corticosteroids or immunosuppressives. Further, premedication with a high dose of intravenous corticosteroids seems to reduce the frequency of infusion reactions. In a study of CD patients reported by Farrell, et al⁴, 6 of 39 (15%) patients with 200 mg intravenous hydrocortisone premedication experienced infusion reactions, in comparison to 10 of 41 (24%) patients with no hydrocortisone premedication. Perhaps 2 doses of oral corticosteroids administered 12 hours and 2 hours before infliximab infusion are more effective in reducing the frequency of infusion reactions. A 2-dose premedication regimen of oral corticosteroids (methylprednisolone 32 mg) roughly 12 and 2 hours before administration of intravenous contrast material provides more significant protection against contrast reactions than a single-dose premedication regimen 2 hours before contrast administration⁵.

In any case, the important point is that infliximab is well tolerated in patients with RA. Infusion related reactions are mild, and few patients stop therapy due to infusion reactions.

GRIGORIOS T. SAKELLARIOU, MD; IOANNIS CHATZIGIANNIS, MD, Director, Department of Rheumatology, St. Paul's Hospital, 551 34, Thessaloniki, Greece. E-mail: sakelgr@otenet.gr or sakellariou.doc@mycosmos.gr

REFERENCES

1. Wasserman MJ, Weber DA, Guthrie JA, Bykerk VP, Lee P, Keystone EC. Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number. J Rheumatol 2004;31:1912-7.

2. Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 2003;348:601-8.

3. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomized trial. Lancet 2002;359:1541-9.

4. Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology 2003;124:917-24.

5. Lasser EC, Berry CC, Talner LB, et al. Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material. N Engl J Med 1987;317:845-9.