Authors
P. BOSSUYT (1), S. CLAEYS (2), S. D'HAENS (3), E. HOEFKENS (3), B. STRUBBE (3), D. MARICHAL (2), L. POUILLON (3), H. PEETERS (2) / [1] Imelda GI Clinical Research Center, Department of Gastroenterology, Imeldaziekenhuis, Bonheiden, Belgium., Bonheiden, Belgium, Department of gastroenterology, [2] St-Lucas IBD Clinic, Department of Gastroenterology, AZ Sint-Lucas, Gent, Belgium., Gent, Belgium, Department of Gastroenterology, [3] Imelda GI Clinical Research Center, Department of Gastroenterology, Imeldaziekenhuis, Bonheiden, Belgium., Bonheiden, Belgium, Department of Gastroenterology
Introduction
Higher infliximab (IFX) drug levels are associated with better outcomes over time in patients with inflammatory bowel disease (IBD). Algorithm based personalized dosing of IFX may prevent loss of response.1 When incorporating point of care testing (POCT) for IFX, ultraproactive therapeutic drug monitoring (TDM) with ad-hoc dose optimisation is possible.
Aim
We aimed to compare the use of an ultraproactive TDM dosing algorithm based on POCT with the use of reactive TDM, by looking at clinical outcomes at 1 year in IFX-treated patients with IBD.
Methods
This was a pragmatic cluster randomized clinical trial in two large IBD centers. All IBD patients with maintenance IFX treatment were prospectively included between June and August 2018. In cohort A, an ultra-proactive TDM algorithm was applied as follows. All patients had an ELISA TL measurement at baseline, of which the result determined the follow-up pathway: (A) TL between 3-7μg/mL: continuation at same dose and interval; (B) TL >7μg/mL: interval prolongation allowed; (C) TL <3μg/mL: interval shortening with minimum 2 weeks, with the next IFX TL measured using a POCT. (i) If the POCT showed an IFX TL <3μg/mL, dose was optimized ad hoc using a linear dosing formula (Dosen = (TLtarget * Dosen-1) / TLmeasured), followed by a new POCT test at next visit with the same interval. (ii) If the POCT showed an IFX TL ≥3µg/mL, no additional dose was given and routine TL testing with ELISA was retaken at next visit. This algorithm was repeated at each visit. In cohort B, a reactive TDM approach was applied with TL measurement only at physician’s discretion (retrospectively assessed to avoid treatement bias). Primary endpoint was failure of IFX therapy, defined as IFX discontinuation, IBD surgery, IBD hospitalization, add-on IBD treatment, and allergic reaction to IFX. Secondary endpoints included sustained clinical remission (phycisian’s global assessement <1 at each visit) and mucosal remission (endoscopy and/or fecal calprotectin) between 6 and 12 months after initiation of the trial.
Results
One hundred eightyseven patients were included (cohort A/B: 115/72, M/F: 95/92, CD/UC: 135/51). Both cohorts had comparable baseline characteristics for disease type, disease duration, IFX duration, and previous treatment. Cohort A had more TL measurements compared with cohort B (8.8/patient/year vs 1/patient/year; p<.0001) leading to a significant higher number of dose optimizations: interval shortening 48% vs 15% (p<.0001), interval prolongation 21% vs 6% (p=.004), bidirectional 13% vs 1% (p=.006). In cohort A, POCT was required in 27% after the first round of ultraproactive TDM and in a mean of 6.3% (SD 1.9%) in the subsequent rounds. Ad-hoc extra dosing was required in 13% of the POCT. After one year of follow-up, no difference was seen in IFX failure 19% vs 10% (p=.08) or IFX discontinuation 11% vs 6% (p=.18) between cohort A and B. Sustained clinical remission rates were comparable in both cohorts (75% vs 83%; p=.17). Mucosal remission data were available in 71 patients (38%). In this subgroup, mucosal remission was more frequently seen in the reactive TDM cohort (79%) than in the ultraproactive TDM cohort (52%) (p=.021).
Conclusions
This is the first clinical trial comparing an ultraproactive TDM dosing regimen including POCT with reactive TDM dosing during maintenance therapy with IFX in IBD. Although ultraproactive TDM dosing leads to more dose flexibility compared with reactive TDM, this does not result in better clinical outcomes. The value of ultraproactive TDM during induction therapy requires further investigation. 1 Strik et al. Journal of Crohn’s and Colitis 2019:13(S063)
