Rheumatoid arthritis (RA) patients with an inadequate response to the standard regimen of infliximab (RemicadeR) may benefit from a limited dose increase, according to a new study in the April issue of the journal Rheumatology.1 In order to better approximate a real-world clinical setting, the decision to increase dosage was left to individual physicians' judgment of their patients' progress rather than the therapeutic response criteria often used in clinical trials.
In the study, patients who were deemed at week 22 to have an insufficient response to 3 mg/kg infliximab every 8 weeks, plus their standard methotrexate regimen, received a dose increase of infliximab of 100 mg from week 30 onward (for a 150 lb. patient, this represents a 49% dose increase). The dose was increased in 22% of 511 patients, typically in those patients whose baseline disease activity values were highest.
The new regimen often circumvented the partial loss of response, report researchers led by Rene Westhovens, MD, rheumatologist at Universitair Ziekenhuisen Leuven, Belgium. The new study was not randomized or controlled, however, and a regression-to-the-mean-like effect could not be ruled out. "Randomized studies, including the comparison of different infliximab dose escalation regimens to appropriate controls and pharmacoeconomic objectives, are needed," the group concludes.
Significant clinical improvement
Patients' progress with respect to the American College of Rheumatology (ACR) therapeutic response criteria were assessed at week 22. At this point, 61.4%, 34%, and 14% of patients met the ACR20, -50, and -70 criteria, respectively. Moreover, 6.1% of patients were in clinical remission. A low swollen joint count at baseline correlated with improvement at week 22 for all of these measures. Finally, changes in Health Assessment Questionnaire scores between weeks 0 and 22 effectively predicted therapeutic response at week 54.
In the ATTRACT (Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy) trial,2 which is considered the benchmark study of infliximab therapy in RA, patients stayed in a single dosing regimen, which became the proposed standard of care. This regimen, however, had a tendency to be less effective than either a higher dose of 10 mg/kg every 8 weeks or a shorter perfusion interval of 3 mg/kg every 4 weeks. Some clinicians felt that this dose did not take into account which measurements of response are relevant in daily practice, and suggested that certain patients could benefit from a higher dose. The current study sought to take into account the clinical judgment of individual physicians to determine the appropriate course of therapy for their patients.
"The approach from Belgium is a reasonable one for patients who are not responding," Martin Bergman, MD, assistant clinical professor at MCP Hahnemann University in Philadelphia and rheumatologist at Taylor Hospital in Ridley Park, Pennsylvania, tells CIAOMed. The new study "suggests that all I need to do is increase the dose by 1 vial (100 mg) to get a decent response, without increasing interval," he says. "This should be more convenient to the patient, as less frequent dosing intervals will result in less frequent disruption of their daily routine, and less time off from work."
As it stands, "the current practice, for me, is completely subjective, dependent on my opinion of how active the disease remains," Dr. Bergman says. For example, he indicates that in patients who were doing relatively well, but are having a slight increase in their disease activity, he will usually increase the dose to 5mg/kg, but continue dosing on the same bimonthly interval.
"If there is a greater increase in disease activity, sometimes I will keep them on the same 3mg/kg dose but increase the frequency to every 6 weeks," he says, "but in most cases, when there is significant activity, I'll do both. If at around 3 months I haven't seen any response, I'll switch to a different agent."
References:
- Durez P, Van den Bosch F, Corluy L, et al. A dose adjustment in patients with rheumatoid arthritis not optimally responding to a standard dose of infliximab of 3 mg/kg every 8 weeks can be effective: a Belgian prospective study. Rheumatology. 2005;44:465-468.
- Maini R, St Clair EW, Breedveld F et al. Infliximab (chimeric anti-tumor necrosis alpha monoclonal antibody) versus placebo in rheumatoid arthritis receiving concomitant methotrexate: a randomized phase III trial. ATTRACT Study Group. Lancet. 1999;354;1932-1939.