Stability of infliximab dosing in inflammatory bowel disease: results from a multicenter US chart review

Background Infliximab (IFX) therapy escalation during maintenance treatment occurs frequently in clinical practice in patients with ulcerative colitis (UC). Outcomes for these patients have not been described. Aim To describe the prevalence of, and outcomes after, IFX escalation during maintenance therapy in patients with moderate-severe UC. Methods Retrospective observational study of clinical outcomes in ambulatory patients with moderate-severe UC treated with maintenance IFX. Results Fifty-six ambulatory patients received IFX for moderate-severe UC; fifty (89%) responded and proceeded to maintenance therapy. Mean duration of maintenance therapy was 14 months, with mean follow-up of 38 months. Twenty-seven patients (54%) required IFX therapy escalation after a mean of 6 maintenance infusions. Clinical remission was noted in 36% of the entire cohort (18/50) at 12 months; 19% in the escalation group, and 56% in the non-escalation group. Patients who required IFX escalation were less likely to be in clinical remission at 12 months (OR 0.2, 95% CI 0.1-0.6, p=0.01) when compared to those who did not. During the follow-up period, 27% of patients required a colectomy, and the mean time to colectomy was 17 months. Patients in the escalation group required a colectomy in 33% of cases, compared with 21% of non-escalation patients. Conclusions A significant proportion of ambulatory patients with UC treated with maintenance IFX required therapy escalation over time. This was associated with lower remission, and higher colectomy, rates.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Outcomes after escalation of infliximab therapy in ambulatory patients with moderately active ulcerative colitis

Rostholder

Ahmed

Cheifetz

et al. 2012

“…Data from randomised controlled trials (RCTs) and population‐based case series have reported that only ~40% of patients remain in remission or maintain a sustained response at 1 year . This gradual loss of response in many patients has led to empiric biologic dose escalation and a ‘dose‐creep’ phenomenon seen in practice There are many reasons for this secondary loss of response, but often the development of neutralising antibodies in the patient against the therapeutic protein plays a role …”

Section: Introductionmentioning

confidence: 99%

Review article: immunogenicity of anti‐TNF biologics in IBD – the role of patient, product and prescriber factors

Moss

Brinks

Carpenter

2013

SUMMARY BackgroundAnti-drug antibodies (ADAs) to biologic therapies contribute to the loss of response and infusion reactions to anti-TNF drugs in patients with inflammatory bowel disease (IBD). The reasons behind this immunogenicity are complex, and have not been the focus of a dedicated review for prescribers. AimTo provide an overview of the patient, product and prescriber factors, which have been associated with the immunogenicity of anti-TNF therapy, and draw conclusions for clinical practice. MethodsReview of representative observational studies and clinical trials from the IBD and other literature, which report associations with ADA development, with a focus on infliximab and adalimumab. ResultsADAs develop in 10-20% of patients receiving anti-TNF maintenance therapy, and these patients are three times more likely to lose response as ADA-negative patients. Patient genotype plays a role in ADA risk in a minority of patients, but age or disease type is not a major factor. Drug mishandling, such as agitation or freeze-thaw cycles, can induce protein aggregates, which are known to be immunogenic. Prescription of maintenance therapy with concomitant immunomodulators, and achieving suitable trough drug levels, reduces the risk of ADAs in patients with IBD. ConclusionsPatients and prescribers can take several steps to reduce the risk of development of anti-drug antibodies to anti-TNF antibodies. Further research is required to determine if immunogenic factors identified in other situations apply to use of anti-TNFs in IBD.

“…An increasing number of studies have reported high rates of loss of response to infliximab during maintenance treatment, which is similar to the results of studies on CD . Retrospective multicentre studies conducted in community clinics and university hospitals, have reported that up to 40% of patients with UC experienced loss of response to infliximab, which was more common than that reported in patients with CD . By analogy with the data available in CD patients, it is hypothesised that dose doubling or interval shortening are as effective in restoring the response to infliximab .…”

Section: Discussionmentioning

confidence: 57%

The outcome of infliximab dose doubling in 157 patients with ulcerative colitis after loss of response to infliximab

Dumitrescu

Amiot

Seksik

et al. 2015