Introduction Loss of response to Infliximab or Adalimumab therapy is commonly encountered during the course of treatment in patients with refractory Crohn’s disease (CD). The aim of this study was to evaluate the safety and efficacy of dose intensification; defined as either double-dosing or decreasing interval of anti-tumour necrosis factor (TNF) therapy in patients with refractory CD, who have lost response to standard dose treatment.
Methods A retrospective interrogation of our local inflammatory bowel disease database at Queen Elizabeth Hospital, Woolwich was undertaken to identify all patients who had had either dose-doubling or decreased dosing intervals of their anti-TNF therapies. Clinic letters, hospital notes, biochemical, endoscopic and radiological data were recorded and disease severity scores calculated using the Harvey-Bradshaw Index. We present our data describing efficacy and safety of these biologic agents at higher dosage.
Results A total of sixteen patients were in our study, 9(56%) female and 7(44%) male and the mean age was 38 years (range 21 – 68 years). Median disease duration was 6 years (range 2 – 13 years). There were 12 patients who were initially started on Infliximab while 4 had Adalimumab as their initial biologic therapy. 11(69%) patients had dose-doubling and 5(31%) patients had decreased dosage intervals due to secondary loss of response to initial anti-TNF at standard dosage regimen. Early response to dose-escalation was experienced by 9/16 (56%) patients while 7/16(44%) patients failed to respond to alteration in anti-TNF therapy regimen. Of the nine patients who initially showed response to intensified regimens, sustained clinical remission was maintained in 5(31%) patients at 12 months and this cohort was successfully weaned of biologic therapy. There was secondary loss of response in 4(25%) patients after median of 7.5 months (range 6–10) at this intensified regimen. No adverse effects were noted in our cohort of patients at this intensified regimen.
Conclusion Our experience of managing CD patients who have failed on their initial standard dose biological therapies has showed that there is certainly value in trialling either increased dosage or decreased dosing intervals of anti-TNF agent. Five patients achieved sustained clinical response and 4 patients had a median further 7 months of disease control prior to relapse. Higher anti-TNF dosage appears to be well tolerated and safe in CD. Of the patients who did fall in the latter two groups, there was a tendency towards reducing the dosing intervals as the more successful strategy above dose-doubling; however this was not statistically significant.
Disclosure of Interest None Declared.
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