Patients on high-dose infliximab may develop antibodies that reduce efficacy

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Patients on high-dose infliximab may develop antibodies that reduce

efficacy



Mar 15, 2006



Gandey







Montreal, QC - Researchers say they may be narrowing in on a possible

causal relationship between the presence of high concentrations of

antibodies to infliximab (Remicade, Centocor) and the need for

escalating doses in patients with rheumatoid arthritis (RA). " This is

the first time in RA that we are seeing a need for higher doses of

infliximab, " lead author Dr Boulos Haraoui (Hospitalier de

l'Université de Montréal, QC) told rheumawire. " The development of

more antibodies may explain why. " The findings are published in the

January 2006 issue of the Journal of Rheumatology [1].

The researchers explain that because infliximab is a chimeric

molecule that is partially of murine origin, some patients develop

human antichimeric antibodies. They suggest that the incidence of

anti-infliximab antibody development depends on the dose and dosing

regimen of infliximab, as well as use of concomitant corticosteroids

or other immunosuppressant medications.

In this Amgen-sponsored study, the researchers evaluated whether

infliximab at doses greater than 3 mg/kg every eight weeks is

associated with differences in baseline clinical characteristics or

anti-infliximab antibodies.

The team looked at 51 consecutive RA patients treated with infliximab

at a single center. They retrospectively evaluated baseline clinical

characteristics and anti-infliximab levels. They divided patients in

two groups. Group 1 achieved and maintained clinical responses with

infliximab. Group 2 patients required higher doses.

Group 2 patients included those who required a dose increase to

achieve or maintain a clinical response. Group 2a patients did not

achieve a clinical response by week 14 but subsequently achieved a

clinical response to a higher dose of infliximab. Group 2b patients

achieved an initial clinical response by week 14, but later required

a dose increase to maintain this response.

Infliximab levels and anti-infliximab antibodies in patients with RA



Clinical characteristics

Group 1 (n=19)

Group 2 (n=32)

Group 2a (n=32)

Group 2b (n=21)

Serum samples tested, mean (standard deviation)

3.1 (1.1)

3.5 (0.9)

3.5 (1.0)

3.6 (0.8)

Patients with >1 informative sample, n (%)

14 (74)

19 (58)

8 (73)

11 (50)

Patients with anti-infliximab antibodies, n (%)

4 (29)

9 (47)

4 (50)

5 (45)

Maximum µg/mL concentration, mean (SD)

7.5 (4.8)

18.3 (8.9)

15.3 (12.9)

20.7 (4.2)

Levels >8 µg/mL, %

25

78

75

80



To download table as a slide, click on slide logo below

The researchers found that 63% of patients required an increased dose

of infliximab. They observed no statistically significant differences

in baseline or clinical characteristics between those who required

dose escalation and those who did not.

They identified anti-infliximab antibodies in 47% of Group 2 vs 27%

of Group 1 patients. The researchers found the highest antibody

concentrations in Group 2 patients (mean + SD: 18.3+8.9 g/mL vs 7.5

+4.8 g/mL; p=0.02). They observed that patients who developed anti-

infliximab antibodies were about 10 years younger and were taking

less prednisone at the time of infliximab initiation.

During an interview with rheumawire, Haraoui pointed out that this

finding presents unique challenges for clinicians. " It is very hard

for the practicing physician. For one, the assay we used is not

readily available so it would be difficult to initiate this kind of

testing. " And he adds that as higher doses of infliximab become

required for some patients, the economic burden can be overwhelming.

" Switching to another anti-TNF may be the best option. "

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