Drug concentrations, immunogenicity predict anti-TNF treatment failure

Reuters Health Information: Drug concentrations, immunogenicity predict anti-TNF treatment failure

Drug concentrations, immunogenicity predict anti-TNF treatment failure

Last Updated: 2019-03-07

By Reuters Staff

NEW YORK (Reuters Health) - About one-quarter of patients with active luminal Crohn's disease (CD) do not respond to anti-tumor necrosis factor (TNF) drugs, while about two-thirds don't achieve remission, according to new research.

The findings, online February 26 in The Lancet Gastroenterology & Hepatology, come from the largest prospective study yet of anti-TNF therapy in inflammatory bowel disease (IBD).

"Anti-TNF treatment failure is common and is predicted by low drug concentrations, mediated in part by immunogenicity," Dr. Tariq Ahmad of the University of Exeter, U.K., and colleagues write. "Clinical trials are required to investigate whether personalised induction regimens and treatment-to-target dose intensification improve outcomes."

Up to 40% of patients have a primary non-response to anti-TNF treatment, while 24% to 46% stop responding during the first year of treatment, Dr. Ahmad and his team note. To investigate factors associated with treatment failure, they enrolled 1,610 patients from 120 National Health Service trusts, including 955 on infliximab (753 on originator, 202 on biosimilar) and 655 on adalimumab.

Among patients who could be assessed, 23.8% had primary non-response at week 14, 63.1% were not in remission at week 52, and 7.8% stopped treatment due to adverse events.

Drug concentration at week 14 was independently associated with primary non-response and non-remission. Optimal drug concentrations for remission were 7 mg/L for infliximab and 12 mg/L for adalimumab.

Immunogenicity occurred in 62.8% of patients on infliximab and 28.5% with adalimumab. Taking an immunomodulator was associated with a significantly reduced risk of immunogenicity with both drugs (hazard ratio, 0.39 with infiximab, 0.44 with adalimumab).

Factors associated with low drug concentrations included obesity, smoking, low albumin concentrations, higher baseline disease activity and development of immunogenicity.

"Concomitant immunomodulator use and dose intensification in at-risk individuals during induction might improve the effectiveness and durability of treatment," Dr. Ahmad and colleagues write. "Reassuringly, treatment ineffectiveness, safety, and immunogenicity of originator infliximab are no different to the biosimilar, which removes some of the cost constraints of dose intensification. Further clinical trials are required to better understand whether these strategies can allow us to improve the effectiveness and durability of anti-TNF therapy."

Dr. Ahmad was not available for an interview by press time.

SOURCE: https://bit.ly/2TkvZ2k

Lancet Gastroenterol Hepatol 2019.

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