Medication persistence is highest with non-anti-TNF agents ustekinumab in Crohn’s disease and vedolizumab in ulcerative colitis compared to other biologics, according to an Australian study.

The Persistence Australian National IBD Cohort (PANIC) study, published in Alimentary Pharmacology and Therapeutics, compared medication persistence across four biologic agents in 2,499 patients with 8,219 person-years of follow-up.

The study found ustekinumab-treated patients with luminal Crohn’s disease were more likely to experience medication persistence than those treated with anti-TNF agents (HR: 1.79, 95%CI: 1.32-2.38 P < 0.01).

“Ustekinumab 12-month persistence was 80.0%, followed by vedolizumab 73.5%, infliximab 68.1% and adalimumab 64.2% (P = 0.01). Persistence of ustekinumab in luminal Crohn’s disease remained the highest as first-, second- and third-line therapies,” the study said.

In moderate-severe ulcerative colitis, vedolizumab patients were more likely to experience medication persistence than those receiving anti-TNF agents (HR: 1.67, 95%CI: 1.27-2.18 P < 0.001).

“Vedolizumab 12-month persistence was 73.4%, followed by infliximab 61.1%, and adalimumab 45.5% (P < 0.001).”

“Persistence rates of vedolizumab in moderate-severe ulcerative colitis remained the highest as first-line therapy but not in second or third lines,” the study said.

The study found no difference in persistence between infliximab and adalimumab in fistulising Crohn’s disease.

Thiopurine co-therapy increased the persistence of anti-TNF agents in both Crohn’s disease and ulcerative colitis but did not significantly affect the persistence of ustekinumab or vedolizumab.

Methotrexate co-therapy also significantly increased the persistence of anti-TNF agents in Crohn’s disease but not in ulcerative colitis.

“We hypothesise that the improved persistence of ustekinumab and vedolizumab vs anti-TNF agents may be associated with reduced immunogenicity from their production using phage display transgenic technology, in contrast to the more immunogenic mouse chimeric or humanised structures of anti-TNF agents,” the study said.

“Anti-TNF drugs also are associated with a wider range of adverse effects and less favourable safety profile, especially in vulnerable populations, which may have led to out-of-class treatment switches. “

The study identified first-line therapy as one of factors which increased the persistence of biological agents and progressive worsening of persistence with later lines of therapy.

“Not only was the second-line choice significantly poorer in persistence than the first-line choice, but third or-higher line choices were significantly worse than second line (P < 0.001).”

“This translatable observation supports the need to optimise not only the initial chosen biological agent prior to switching, but also with every subsequent selection,” the study said.

Senior investigator Professor Rupert Leong, from the Concord Repatriation General Hospital, told the limbic that medication persistence provided the best evidence in the absence of head to head trials.

He said the composite marker of efficacy and safety as well as patient and physician preferences, was a useful way of assessing and comparing different drugs.

“It is evidence to recommend starting patients on the non-anti-TNFs first but for some patients there might be different reasons to select an anti-TNF first, for example if they have got extraintestinal manifestations that are very much TNF driven.”

“So, for example, ankylosing spondylitis where anti-TNFs are also indicated for treatment of that condition. Vedolizumab or ustekinumab would not be effective for some of those severe extraintestinal manifestations.”

Professor Leong said the Australian data was useful given a lot of patients go onto first line therapies for these newer non-anti-TNF agents here.

In comparison, there is less first line evidence on the non-anti-TNF drugs in Europe due to prescribing restrictions.

Disclosures: Professor Leong has served as a speaker and/or an advisory board member for AbbVie, Arena, Aspen, BMS, Celgene, Chiesi, Ferring, Gutagen, Hospira, Janssen, MSD, Novartis, Pfizer, and Takeda, and has received research funding from Shire, Janssen and Takeda.