Demographic and clinical characteristics of the 38 patients included are shown in table 1. Four patients were lost to follow‐up before week 54: one wanted to become pregnant, one preferred to be treated in a hospital nearby and two because of comorbidities.
There was a significant decrease in BASDAI, morning stiffness, global disease activity and C‐reactive protein after 24 and 54 weeks of treatment (table 1) and all pre‐treatment samples showed undetectable infliximab levels and no anti‐infliximab. We did not detect anti‐infliximab in the presence of infliximab.
After 24 weeks, 24 patients (63%) met ASAS‐20 response criteria. Responders showed higher mean serum trough infliximab levels, and only two patients (8%) showed anti‐infliximab, compared with 5 (36%) of the non‐responders (p
After 54 weeks of treatment, ASAS‐20 response criteria were met by 21 patients (53%). The mean serum trough infliximab level for responders was significantly (p<0.01) higher that that of the non‐responders (8.2 mg/l vs 6.3 mg/l; figure 1) and anti‐infliximab was significantly (p<0.04) more often found in non‐responders. Only 5% (1 of 21) of the responders showed anti‐infliximab, compared with 59% (10 of 17) of the non‐responders.
In total, 9% (1 of 11) patients with detectable anti‐infliximab was classified as a responder at week 54, compared with 74% (20 of 27) of patients without anti‐infliximab (figure 2).
After correction for probable confounding variables such as gender and human leucocyte antigen B27 (HLA‐B27), the absence of anti‐infliximab remained a significant determinant for ASAS‐20 response, with an odds ratio (OR) of 100 (95% CI 5.2 to 1000). Remarkably, the presence of anti‐infliximab was significantly associated with the absence of HLA‐B27 (OR
7.1; 95% CI 1.1 to 47.6; Pearson χ2
Two weeks after the infusion of week 24, significantly lower infliximab levels were measured (20 mg/l compared with 51 mg/l; p<0.01) in patients who developed anti‐infliximab within 54 weeks of treatment.
In 12 patients, dose was increased within the 54 weeks, because of insufficient clinical response. Nine (75%) of these patients showed anti‐infliximab antibodies. Increase in dose did not result in a significant increase of the serum trough infliximab level (p
0.33), or a significant decrease in the anti‐infliximab level (p
0.90) and BASDAI (p
0.39). However, 2 of 12 patients reported longer duration of effect.
Infusion reactions occurred in six patients. Most reactions were mild, and all patients recovered after supportive therapy. Treatment with infliximab was stopped in each case. Every infusion reaction was preceded by development of anti‐infliximab and consequently undetectable serum trough infliximab levels. All antibodies to infliximab consisted of IgG1 and IgG4 subtypes. Although these infusion reactions resemble a type 1 allergic reaction, no IgE was detected. One patient's pre‐infusion serum contained an anti‐infliximab level of 6.4 g/l, indicating that approximately half of his total serum IgG consisted of infliximab‐specific antibodies.