TAXITMust knowUC and CD · Drug monitoring
Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease
Vande Casteele N, et al.
Gastroenterology 2015 · PMID 25724455 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2015.02.031 (full paper, opens in a new tab)
| Endpoint | Trough-based | Clinically based | Difference |
|---|---|---|---|
| Clinical and biochemical remission, 1 year (primary endpoint) | 69% | 66% | P=0.686 |
| Relapse during the year, Lower is better | 7% | 17% | 9 (7%) vs 21 (17%) patients; P=0.018 |
After the shared optimisation phase, continued trough-based dosing did not raise remission over clinically based dosing, though relapses were fewer.
Source: Vande Casteele 2015, abstract. Randomised: 128 trough-based, 123 clinically based.
Structured abstract
BackgroundInfliximab dosing is usually adjusted on symptoms. Whether targeting a trough level improves remission, or simply uses the drug more efficiently, had not been tested in a randomised trial.
Methods1-year randomised controlled trial at a single tertiary referral centre (Leuven, Belgium), after an open optimisation phase. 263 patients. Primary endpoint: Clinical and biochemical remission 1 year after the optimisation phase.
ResultsPrimary result. 69% with trough-based dosing vs 66% with clinically based dosing; P=0.686 (not significant).
Take-homeA one-time optimisation to an infliximab trough of 3–7 µg/mL is worthwhile (fewer relapses, lower cost when levels are high), but repeated proactive trough-based dosing did not increase 1-year remission.
| Patients | 263 |
|---|---|
| Population | Adults with Crohn's disease (178) or ulcerative colitis (85) with a stable response to maintenance infliximab. All were first dose-adjusted to a trough of 3–7 µg/mL; 251 were then randomised. |
| Comparison | Continued trough-based (proactive) dosing (n=128) vs dosing based on clinical features (n=123) |
| Drugs | infliximab |
| Classes | Anti-TNF |
| Published | Vande Casteele N, et al. Gastroenterology 2015;148:1320–9.e3. |
Key points
- At screening, only 43.7% (115/263) had a trough of 3–7 µg/mL.
- Of 76 patients with a trough below 3 µg/mL, 69 (91%) reached target after dose escalation; in Crohn's disease this raised remission from 65% to 88% (P=0.020) and lowered median CRP (4.3 to 3.2 mg/L; P<0.001). No such change was seen in UC.
- Of 72 patients with a trough above 7 µg/mL, 67 (93%) reached target after dose reduction, cutting drug cost by 28% (P<0.001) without loss of control.
- Relapse during the year: 17% (21 patients) with clinically based dosing vs 7% (9) with trough-based dosing; P=0.018.
- TAILORIX (122 biologic-naive adults with active Crohn's disease on infliximab plus an immunosuppressant) found no benefit from escalating on symptoms, biomarkers and drug levels vs symptoms alone: 33% (15/45) and 27% (10/37) vs 40% (16/40) reached sustained steroid-free remission with no ulcers at week 54; P=0.50 (PMID 29317275).
Limitations
- Single centre; patients were already in stable response on maintenance infliximab.
- All patients were optimised before randomisation, so the trial compared strategies after both arms had reached target.
- Composite remission endpoint; no endoscopic outcome.
Commentary
TAXIT is the first randomised trial of proactive therapeutic drug monitoring (TDM) in adult IBD. Its practical legacy is the optimisation phase: many patients on maintenance infliximab are outside the 3–7 µg/mL range, escalation helps those with low troughs in Crohn’s disease, and de-escalation is safe and saves money in those with high troughs.
The randomised comparison was negative, as was TAILORIX during induction and early maintenance, and adult guidelines have generally favoured reactive testing at loss of response. Later evidence: in NOR-DRUM B, a larger multi-disease maintenance trial with a structured algorithm for dose and interval changes, proactive TDM did improve sustained disease control. Higher targets are often used for perianal disease (see PISA-II).
Journal club
Design
1-year randomised controlled trial at a single tertiary referral centre (Leuven, Belgium), after an open optimisation phase. 263 patients.
Primary result. 69% with trough-based dosing vs 66% with clinically based dosing; P=0.686 (not significant).
Validity and applicability
- Single centre; patients were already in stable response on maintenance infliximab.
- All patients were optimised before randomisation, so the trial compared strategies after both arms had reached target.
- Composite remission endpoint; no endoscopic outcome.
Where it sits now
A one-time optimisation to an infliximab trough of 3–7 µg/mL is worthwhile (fewer relapses, lower cost when levels are high), but repeated proactive trough-based dosing did not increase 1-year remission.
- NOR-DRUM B (2021): In patients on maintenance infliximab, scheduled drug-level monitoring with a dosing algorithm kept more patients in sustained disease control over a year than standard dosing without levels.
- PISA-II (2022): For a high perianal fistula with a single internal opening, surgical closure after seton and short anti-TNF gives more MRI healing and fewer reinterventions than anti-TNF alone, and MRI healing predicts durable closure.
Questions for discussion
- Both arms were optimised to 3–7 µg/mL before randomisation. What question did the randomised phase actually answer?
- Relapses were fewer with trough-based dosing although remission was similar. Which outcome would you use to justify proactive monitoring?
- How does TAXIT fit with TAILORIX and SERENE-CD, which also found no clear benefit from proactive, level-guided dosing?