Introduction The increasing use of anti-TNF drugs in Crohn's disease reflects their efficacy. Unfortunately, even with scheduled maintenance therapy, secondary loss of response is common affecting approximately 10%–15% of patients/year. Increasing drug levels, whether by doubling the dose or decreasing the interval, recaptures response in approximately 75% of patients. However, both of these strategies have cost implications. Anecdotal reports suggest that in patients losing response on maintenance infliximab (IFX) 5 mg/kg, a temporary increase to double doses (DD; 10 mg/kg) can lead to subsequent recapture of response at the lower dose. In a small cohort, we have previously shown that this strategy was not viable in the majority of patients. We now present an extended cohort across two centres with longer follow-up.
Methods We performed a retrospective review across two tertiary centres of all patients with Crohn's disease who had received temporary increases to DD of IFX for loss of response. Demographic data, HBI prior to the first infusion at the higher dose and prior to the first infusion at the lower dose, and ability to continue on IFX at 5 mg/kg were recorded.
Results 34 patients (18M:16F, median age 24 (range 12–51)) received DD IFX for loss of response. Median disease duration was 3 years (range 0–32) and the median time to dose increase from starting IFX was 12 months (range 3–60). All had received standard induction doses of IFX at 5 mg/kg on weeks 0, 2 and 6 and were on scheduled maintenance therapy. The dose interval prior to dose increase was 8 weeks for 24 patients, 7 weeks for 1, and 6 weeks for 9. 26 patients were on concurrent immunomodulators and 8 were not. One patient received 4 DD, 27 received 2 DD and six patients 1 DD. Dose increase was effective in the short term with the median HBI falling from 6 (range 0–27) prior to the first infusion at 10 mg/kg, to 1 (0–7) prior to the first infusion back at the standard dose (5 mg/kg) (p=0.003). However, only seven patients remained on IFX at the end of follow-up (median 13 months (range 8–25)). The median interval to discontinuing IFX was 4 months after the first DD (1–19). Of those who discontinued, four had infusion reactions while the others failed to maintain a response to IFX.
Conclusion Because of the limited treatment options available in Crohn's disease, attempting to recapture response in patients on IFX is appropriate. However, while temporary double-dosing is effective in the short term, it does not deliver long term disease control after subsequent dose reduction. Whether dose reduction is possible after prolonged dose increase remains to be answered.
Competing interests None declared.