medwireNews: The clinical benefit of infliximab dose escalation in people with rheumatoid arthritis (RA) may be limited to the initial two escalations, US study findings indicate.
Stanley Cohen (Metroplex Clinical Research Center, Dallas, Texas, USA) and colleagues report that “[t]here does not appear to be a clinical benefit in infliximab dose escalations above the equivalent of 5 to 7 mg/kg.”
Their findings are based on an analysis of 185 patients (72% women, mean age 58 years) enrolled in the US Corrona RA registry who began infliximab treatment at a dose of 3 mg/kg every 8 weeks and subsequently received at least one dose escalation of the tumor necrosis factor inhibitor within 12 months of initiation.
Dose escalation was defined as an increase of more than 1 mg/kg in dose and/or an increase in the frequency of infusion by at least 1 week, with all doses standardized to mg/kg every 8 weeks to allow for direct comparisons.
The researchers report that patients who received two infliximab dose escalations (n=101) – typically from 3 mg/kg to 5 or 7 mg/kg every 8 weeks or from 3 mg/kg every 8 weeks to 5 mg/kg every 8 weeks then every 6 weeks – had a mean estimated CDAI that was a significant 7.63 points lower than the baseline value of 23.68 points at the time of the first dose escalation and a further 2.85 points lower at the second escalation.
In the patients who received three dose escalations (n=42), the mean estimated CDAI had fallen by a significant 4.24 points from a pretreatment value of 22.69 points at the time of dose escalation one and by a further 6.55 points up to escalation two. However, it then increased by an estimated 4.29 points between the second and third dose escalation.
And for those patients who received four or more dose escalations (n=12), the estimated mean CDAI remained stable over time, “demonstrating little impact from dose escalations,” in this group, Cohen and team remark.
When the investigators compared mean CDAI with actual infliximab dose rather than the number of escalations, they found that predicted mean disease activity decreased when the dose was increased from 3 mg/kg to 5 mg/kg every 8 weeks but then remained stable up to a dose of 10 mg/kg every 8 weeks.
The researchers also found that “[d]ose escalation had little impact on mean HAQ scores.” Specifically, the scores were stable among patients who received two or three dose escalations, but initially decreased then gradually increased from the second through the fifth dose escalation among the patients who received four or more escalations.
Writing in Clinical Rheumatology, Cohen et al say that their study “supports the practice of infliximab dose escalation but suggests that there may be diminishing clinical benefit beyond the initial dose escalations.”
They continue: “This may have important clinical implications, as higher doses may be associated with increased toxicity and cost while only maintaining disease activity levels.”
And the authors conclude: “As multiple other options exist for the treatment of RA, consideration of switching therapy after 1 to 2 dose escalations is supported by these observations.”
By Laura Cowen
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