NOR-DRUM BUC and CD · Drug monitoring
Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial
Syversen SW, et al.
JAMA 2021 · PMID 34932077 (PubMed, opens in a new tab) · doi 10.1001/jama.2021.21316 (full paper, opens in a new tab)
| Endpoint | Proactive TDM | Standard therapy | Difference |
|---|---|---|---|
| Sustained disease control, No disease worsening over 52 weeks (primary endpoint) | 73.6% | 55.9% | Adjusted difference 17.6% (95% CI 9.0–26.2); P<0.001 |
The result is pooled across six diseases, and the comparator was no monitoring at all rather than reactive testing.
Source: Syversen 2021, abstract (full analysis set of 454 patients; 167 vs 127 patients reached the endpoint). The difference is adjusted.
Structured abstract
BackgroundProactive drug monitoring, with scheduled drug and antibody levels and dose adjustment, had been proposed to optimise infliximab, but whether it improved outcomes during maintenance therapy was unclear.
MethodsRandomised, parallel-group, open-label trial (20 Norwegian hospitals); 52 weeks. 458 patients. Primary endpoint: Sustained disease control without disease worsening over 52 weeks (disease-specific composite scores, or patient and physician agreement on worsening leading to a major treatment change).
ResultsPrimary result. 73.6% (167 patients) with proactive TDM vs 55.9% (127) with standard therapy; adjusted difference 17.6% (95% CI 9.0–26.2); P<0.001.
Take-homeIn 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.
| Patients | 458 |
|---|---|
| Population | Adults on maintenance infliximab for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn's disease or psoriasis. 454 included in the full analysis set. |
| Comparison | Proactive TDM (scheduled drug and antidrug antibody levels with dose and interval adjustment; n=228) vs standard infliximab therapy without level monitoring (n=230) |
| Drugs | infliximab |
| Classes | Anti-TNF |
| Published | Syversen SW, et al. JAMA 2021;326:2375–84. |
Key points
- Adverse events: 60% (137) with TDM vs 63% (142) with standard therapy.
- The companion NOR-DRUM A trial tested proactive TDM during infliximab induction (411 adults): week 30 clinical remission 50.5% (100/198) vs 53.0% (106/200); adjusted difference 1.5% (95% CI −8.2 to 11.1); P=0.78 (PMID 33944876).
- So proactive TDM helped in maintenance but not during induction.
- Results are pooled across six immune-mediated diseases; the comparator was no monitoring, not reactive TDM.
Limitations
- Open-label.
- Mixed population; IBD-specific effects cannot be read reliably from the pooled result.
- Compared with no monitoring rather than reactive TDM; long-term complications and cost-effectiveness were not assessed.
Commentary
NOR-DRUM B is the largest randomised trial supporting proactive therapeutic drug monitoring (TDM) in adults. Earlier adult trials, TAXIT and TAILORIX (PMID 29317275), did not show a benefit, while the paediatric PAILOT trial did.
How to use it: proactive monitoring during infliximab maintenance is reasonable. Many clinicians use it selectively, for example when a loss of response would be costly (few remaining options, previous antidrug antibodies) or when infliximab is given without an immunomodulator. NOR-DRUM A shows that scheduled levels during induction alone add little. The authors called for trials comparing proactive with reactive TDM and for cost-effectiveness data.
Journal club
Design
Randomised, parallel-group, open-label trial (20 Norwegian hospitals); 52 weeks. 458 patients.
Primary result. 73.6% (167 patients) with proactive TDM vs 55.9% (127) with standard therapy; adjusted difference 17.6% (95% CI 9.0–26.2); P<0.001.
Validity and applicability
- Open-label.
- Mixed population; IBD-specific effects cannot be read reliably from the pooled result.
- Compared with no monitoring rather than reactive TDM; long-term complications and cost-effectiveness were not assessed.
Where it sits now
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.
- TAXIT (2015): 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.
- PAILOT (2019): In children on adalimumab, proactive trough monitoring with dose adjustment to 5 µg/mL kept far more patients in steroid-free remission than reactive testing.
Questions for discussion
- Results were pooled across six diseases. How confident are you that the effect applies to IBD specifically?
- The comparator had no drug levels at all. How might the result differ against reactive drug monitoring, which is common practice?
- The companion NOR-DRUM A trial found no benefit during induction. Why might proactive monitoring help in maintenance but not in induction?