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Copyright ©The Author(s) 2021.
World J Gastroenterol. Oct 7, 2021; 27(37): 6231-6247
Published online Oct 7, 2021. doi: 10.3748/wjg.v27.i37.6231
Table 2 A list of the main trials looking at both reactive and proactive therapeutic drug monitoring
Ref.
Study design; n
Population studied
Type of intervention
Primary outcome
Results
Vande Casteele et al[16], 2015 (Proactive)Prospective single center study RCT, n = 263Adults with mod to severe UC responders to infliximab (IFX)IFX. Target 3-7 μg/mL during maintenance phase. Clinical vs concentration-based dose escalationClinical and biochemical remissionFewer flares in concentration-based group. No difference in remission rates at 1 yr
Papamichael et al[73], 2017 (Proactive)Retrospective multi-center RCT, n = 264Adults with CD + UCIFX 5-10 μg/mLTreatment failureNeed for IBD related hospitalization or surgery. Adverse eventsProactive was associated with better clinical outcomes, including greater drug durability, less need for IBD-related surgery or hospitalization
Perinbasekar et al[74], 2017 (Proactive)Retrospective single center study, n = 127Adult IBD patients initiating treatment with either IFX or adalimumab (Ada)IFX target ≥ 3 μg/mL; Ada target ≥ 5 μg/mLClinical response at 1 yr. Endoscopic response. Persistence with anti-TNF at 1 yrPersistence with therapy and clinical and endoscopic response were superior for proactive compared to control patients treated with infliximab
Bernardo et al[75], 2017 (Proactive)Retrospective single center study, n = 117Adult IBD patients on treatment with infliximabClinical based vs proactive TDM. (1) Target IFX CD 3-7 μg/mL; (2) Target IFX UC 5-10 μg/mL; (3) Target Ada CD 5-7 μg/mL; and (4) Target Ada UC 7-9 μg/mLAt 48 wk (1) Clinical remission; (2) Rates of hospitalizations; (3) Rates of surgery; and (4) Therapeutic failureNo difference noted in relation to outcomes. Higher rates of drug escalation in proactive group. Longer period of remission in proactive group
D’Haens et al[12], 2018 (Proactive)Prospective multi-center RCT, n = 122Adults with mod to severe luminal CD biologic naïve on infliximab maintenanceDose escalation using combined approach of clinical + TDM vs symptom-based approach. IFX target > 3 μg/mL during maintenance phaseSustained steroid-free clinical remission at weeks 22-54 and mucosal healing at week 54No difference in terms of rates of steroid-free remission
Papamichael et al[10], 2018 (Proactive vs reactive)Retrospective multicenter study, n = 102Adult IBD patients on infliximabReactive TDM followed by subsequent proactive TDM vs reactive testing IFX target 5-10 μg/mLTreatment failure. IBD related hospitalization and surgeryProactive monitoring after reactive testing associated with greater drug persistence and fever IBD related hospitalizations
Papamichael et al[11], 2019 (Proactive)Retrospective multicenter study, n = 382IBD patients on maintenance therapy with adalimumabProactive vs reactive TDM. Ada > 10 μg/mLTreatment failureProactive associated with lower risk of treatment failure
Assa et al[14], 2019 (Proactive)Prospective multi-center RCT, n = 78Ages 6-17 yr with CD with response to adalimumabAda target trough levels ≥ 5 μg/mLSustained steroid-free clinical remission (weeks 8-72)Higher rates of steroid free clinical remission in proactive group
Strik et al[76], 2019 (Proactive)Retrospective multi-center RCT, n = 80 UC + CD in clinical remission on infliximab maintenance therapyDashboard driven dose escalation with TDM vs non TDM. IFX level > 3 μg/mLClinical remissionDashboard-guided dosing resulted in a significant higher proportion of patients who maintained clinical remission during 1 yr of treatment
Danese et al[70], 2020 (Proactive)Prospective multi-center RCT, n = 184Clinical responders from induction phase of SERENE-CDClinical based group vs proactive TDM (TL 5-10 μg/mL) adalimumab every week or every other weekClinical remission and endoscopic response and remission at 1 yrNo difference in terms of clinical end points
Fernandes et al[15], 2020 (Proactive)Prospective study, n = 205IBD patients completing infliximab induction therapyProspective arm (TDM-based dose escalation) vs retrospective arm (non-TDM). IFX levels 3-7 μg/mL CD; IFX levels 5-10 μg/mL UCNeed for surgery, hospital admission, treatment endrates of mucosal healing at 2 yr of treatmentProactive TDM associated with fewer surgeries and higher rates of mucosal healing
Bossuyt et al[71], 2020 (Proactive vs reactive)Prospective multi-center RCTAll IBD patients on infliximab therapy > week 14Using point of care testing at the time of infusion > proactive vs reactive TDMClinical remissionDiscontinuation of infliximab. Composite end points of IBD related hospitalizations and surgeries, change of treatmentNo difference in terms of rate of clinical remission or treatment discontinuationUltra-proactive not superior to reactive
Afif et al[67], 2010 (Reactive)Retrospective study, n =155IBD patients who had infliximabMeasurements of human anti-chimeric antibodies (HACAs) and infliximab concentrationsLoss of response. Change in treatmentMeasurement of both antibody and drug levels lead to improved response
Steenholdt et al[66], 2014 (Reactive)Prospective RCT, n = 69CD patients failing on infliximab therapyInfliximab intensification vs algorithm defined using TDMClinical and economic outcomes at week 20Lower healthcare costs in algorithm-based group. Similar rates of clinical response and remission
Kelly et al[63], 2017 (Reactive)Retrospective study, n = 312Primary responders on infliximab who underwent dose escalationTDM vs clinical based dose escalation of infliximabEndoscopic remissionClinical responseHigher rates of endoscopic remission with TDM
Pouillon et al[77], 2018 (Reactive)Retrospective single center study, n = 226IBD patients who completed maintenance phase of TAXITClinical based vs trough concentration-based dosing of infliximab, infliximab level 3-7 μg/mLIBD related hospitalization and surgery. Steroid use. Mucosal healingSimilar rates of mucosal healing in both groups. Higher rates of treatment discontinuation in clinic-based group