Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis

Abstract

ObjectivesTo investigate the possible role of baseline plasma tumour necrosis factor alpha levels (baseline-TNF) on the clinical response to infliximab in patients with rheumatoid arthritis (RA).MethodsPatients with RA refractory to methotrexate received 3, 6, or 10 mg/kg of infliximab every 8 weeks, in a randomised, double-blind manner: the RISING study. Clinical response (disease activity score in 28 joints based on C-reactive protein or American College of Rheumatology core set) at week 54 and serum infliximab levels were compared in three patient groups with low, intermediate, or high baseline-TNF (TNF-low, TNF-int, or TNF-high).ResultsIn TNF-low patients, the clinical response to different doses of infliximab was comparable, whereas TNF-int patients exhibited a dose-dependent trend. In contrast, TNF-high patients (approximately 13% of the total patients) had a clinical response to 10 mg/kg significantly better than the response to 3 and 6 mg/kg of infliximab. In TNF-high patients, the median trough serum levels of infliximab were below the detection limit (<0.1 μg/ml) at 3 and 6 mg/kg but were greater than 2 μg/ml at 10 mg/kg, whereas the levels were approximately 1 μg/ml for each dosage group in TNF-low patients.ConclusionIn patients with RA, baseline-TNF is significantly associated with the clinical response to infliximab in patients with a high baseline-TNF. A higher dose of infliximab may be necessary in these patients, whereas lower doses of infliximab are sufficient for those with a low baseline-TNF. Baseline-TNF may be a useful measure for personalising the treatment of RA using infliximab.

Viewpoint on handling anti-TNF failure in psoriasis

“…increasing the dose or shortening of the administration interval between infusions) has been associated with a significantly increased clinical response compared to changing to another anti-TNF [2]. Another study also reported dose escalation to be a good choice in patients negative for ADAs with low serum infliximab levels [26]. Unfortunately, due to governmental reimbursement restrictions, dose escalation could not be performed in our patient.…”

“…No ADAs were detected, but TSDLs were subtherapeutic. Potential explanations for low TSDLs without ADA formation include patient non-compliance, or an inadequate drug dosage for the degree of inflammation as has been described for infliximab [7,26]. Thus, patient 7 was treated with an increased dose of etanercept.…”

Prediction of Clinical Response After 1 Year of Infliximab Therapy in Rheumatoid Arthritis Based on Disease Activity at 3 Months: Posthoc Analysis of the RISING Study

“…The protocol of the RISING study has been reported previously 3,12 . Patients with active RA, despite MTX treatment, were treated with a standard-dose of IFX (3 mg/kg) at baseline, W2, and W6, after which they were randomized into 3 groups and treated with 3 mg/kg, 6 mg/kg, or 10 mg/kg every 8 weeks from W14 to W46.…”

“…We previously reported that plasma TNF-α levels at baseline were correlated with the clinical responses in both standard-and escalated-dose treatments of IFX 12 . Further, several reports have shown that serum IFX levels and anti-IFX antibodies (ATI) are correlated with clinical response to IFX therapy 3,13,14,15 .…”

Positive association between serum thymic stromal lymphopoietin and anti-citrullinated peptide antibodies in patients with rheumatoid arthritis

“…The present study suggests that a TSLP blockade could also have therapeutic potential for patients with RA. If TSLP has become a therapeutic target, we think that measurement of serum TSLP might be useful for determination of drug doses in a manner similar to infliximab [16].…”