TNF-guided infliximab dose escalation does not improve RA remission rates
medwireNews: Adjustment of infliximab dosing based on serum tumor necrosis factor (TNF)-α levels has no impact on rates of remission and sustained treatment discontinuation among patients with rheumatoid arthritis (RA), indicate results from the RRRR trial.
The open-label randomized study included 337 Japanese patients with an inadequate response to methotrexate and no prior infliximab exposure who were given infliximab 3 mg/kg at weeks 0, 2, and 6 followed by either TNF-guided dosing (programmed treatment group), or standard treatment with infliximab 3 mg/kg every 8 weeks (control group) from week 14 onwards. Participants in clinical remission (SDAI≤3.3 points) at week 54 discontinued infliximab.
In the programmed treatment group, 51 patients had low TNF-α levels (<0.55 pg/mL) and received infliximab 3 mg/kg every 8 weeks throughout the study, while 68 patients had intermediate TNF-α levels (0.55 to <1.65 pg/mL) and were given the TNF inhibitor at a dose of 6 mg/kg every 8 weeks for the guided dosing period, and 51 patients had high TNF-α levels (≥1.65 pg/mL) and received infliximab 6 mg/kg at week 14 followed by a further dose increase to 10 mg/kg at 22 weeks and every 8 weeks thereafter.
As reported in the Annals of the Rheumatic Diseases, a comparable 39.4% of 170 patients in the programmed treatment arm and 32.3% of 167 patients in the control group were in clinical remission at week 54 and discontinued infliximab.
There was no significant difference in the proportion of patients who achieved sustained infliximab discontinuation for 1 year – the primary endpoint of the trial – in the programmed treatment and control groups, at 23.5% and 21.6%, respectively.
These findings “did not support our initial hypothesis that deep remission and subsequent sustained discontinuation of [infliximab] can be achieved by intensive and finely tuned treatments with appropriate doses of TNF inhibitors,” write the RRRR (Remission induction by Raising the dose of Remicade in RA) investigators.
Nevertheless, Yoshiya Tanaka (University of Occupational and Environmental Health, Kitakyushu, Japan) and colleagues note that incidence rates of infection and other adverse events were similar across the treatment groups, “suggesting that dose escalation was tolerated in the study.”
In an exploratory analysis, Tanaka et al found that having a baseline SDAI score below 26.0 points was associated with a significantly increased likelihood of achieving sustained infliximab discontinuation for 1 year in both groups, implying that “the success of sustained discontinuation of [infliximab] depends on disease activity at baseline.”
They conclude that “in order to facilitate decision-making by patients and rheumatologists, more efforts are needed to determine the patient profile most likely to benefit from discontinuation of biological DMARDs.”
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