Personalized Anti-TNF Therapy in Crohn's Disease (PANTS)
Research type
Research Study
Full title
Investigation of the clinical, serological and genetic factors that determine primary non-response, loss of response and adverse drug reactions to Anti-TNF drugs in patients with active luminal Crohn's Disease.
IRAS ID
115956
Contact name
Tariq Ahmad
Contact email
Sponsor organisation
Royal Devon and Exeter Hospital NHS Foundation Trust
Research summary
Summary of Results
PANTS enrolled 1610 patients in total; 955 patients treated with infliximab (of which 753 with originator (generic infliximab) and 202 with biosimilar (cheaper version, developed later)) and 655 treated with adalimumab.
295 /1241 patients didn't respond to drug (Primary non-response) when assessed at week 14
764/1211 patients didn't get better (were in non-remission) when assessed at week 54 ,
Adverse events stopped 126/1610 patients.
The only factor independently associated with primary non-response was low drug concentration at week 14.
The optimal week 14 drug concentrations associated with remission at both week 14 and week 54 were 7 mg/L for infliximab and 12 mg/L for adalimumab.Continuing standard dosing regimens after primary non-response was rarely helpful.
Similarly, week 14 drug concentration was also independently associated with non-remission at week 54.
The proportion of patients who developed anti-drug antibodies (immunogenicity) was 62·8% (95% CI 59·0-66·3) for infliximab and 28·5% (24·0-32·7) for adalimumab.For both drugs, suboptimal week 14 drug concentrations predicted immunogenicity, and the development of anti-drug antibodies predicted subsequent low drug concentrations.
Combination immunomodulator (thiopurine or methotrexate) therapy mitigated the risk of developing anti-drug antibodies.
For infliximab, multivariable analysis of immunomodulator use, and week 14 drug and anti-drug antibody concentrations showed an independent effect of immunomodulator use on week 54 non-remission
REC name
South West - Cornwall & Plymouth Research Ethics Committee
REC reference
12/SW/0323
Date of REC Opinion
23 Jan 2013
REC opinion
Further Information Favourable Opinion