Introduction Infliximab(IFX) and adalimumab(Ada) are established treatments for IBD.However, immunogenicity can lead to anti-drug antibodies(ADAb) which is associated with a poor clinical response.Little is known regarding the factors which influence ADAb formation or the long term outcomes.
Methods Patients with detectable ADAb between May 2012 and October 2014 were identified.Assays had been performed using LISA-Tracker DUO Kits which detects free drug levels(DLs) and ADAb only.Patients were analysed for disease phenotype, prior anti-TNF treatment and ADAb formation,and the use of concomitant immunomodulation(IM).
Results 330 IFX DLs and ADAb levels from 199 patients and 143 Ada DLs and ADAb levels from 105 patients were analysed.21 positive ADAb, 19 IFX(9.5%) and 2 Ada(1.9%),were detected with a median ADAb of 141.8 U/ml(range 11–200),all DLs were >1.0μg/ml. 47.6% were male, age range 21–84,median 33.85.7% had Crohn’s Disease.In the majority of patients DL and ADAb were measured due to loss of response(66.7%). 6/19 patients who had IFX ADAb had prior exposure to IFX and 1 had prior exposure to Ada.Time to antibody detection ranged from 2–140 weeks(median 14).Of the 6 patients who had previous exposure to IFX,median time to ADAb detection was 6 weeks.Both patients who developed Ada ADAb had prior exposure to Ada,one also had prior exposure to IFX. 18/21 patients were prescribed concomitant IM(2 methotrexate, 16 thiopurines).8/16 on thiopurines had subtherapeutic TGNs(< 240 pmol/8 x108RBC).
IFX ADAb group(n = 19):11 patients were switched to Ada, all of whom had a clinical response(mean HBI at week 26 = 2.1, no ADAb detected). 1 was switched out of class to vedolizumab and responded well. 3 stopped biologic treatment,1 patient continued on IFX at their own request and 1 patient was dose escalated but failed to respond. 2 patients had concomitant IM optimised,1 of whom on subsequent ADAb testing showed loss of ADAb.
Ada ADAb group(n = 2):1 patient stopped anti-TNF due to recurrent infections and the other was lost to follow up.
Conclusion 42.9% of patients with ADAb had been exposed to anti-TNF previously,all with a gap of >6 months prior to repeat exposure suggesting this is a risk factor for earlier ADAb formation.
All patients switched to Ada from IFX responded well without developing ADAb,highlighting that switching to another anti-TNF is an acceptable option before switching out of class.
Our use of concomitant IM is high but 50% of this cohort had subtherapeutic TGNs.The 2 patients in whom a thiopurine was optimised achieved clinical remission while remaining on IFX. However the level at which TGNs should be targeted in this context is still unclear
Disclosure of Interest B. Warner: None Declared, E. Johnston: None Declared, J. Digby-Bell: None Declared, Z. Arkir: None Declared, N. Unsworth: None Declared, S. Anderson: None Declared, J. Sanderson: None Declared, P. Irving Grant/research support from: PI has been advisor to, in receipt of educational or research grants from, or invited lecturer for Abbvie, Falk, Ferring, Genetech, Hospira, Merck, Pharmacosmos, Shire, Takeda, Tillotts, Topivert, Vifor and Warner Chilcott, Paid instructor for: as above