SERENE-CDCD · Biosimilars and dosing
Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies: Randomized SERENE CD Trial Results
D'Haens GR, et al.
Gastroenterology 2022 · PMID 35122766 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2022.01.044 (full paper, opens in a new tab)
| Endpoint | Higher dose | Standard dose | Difference |
|---|---|---|---|
| Clinical remission, Week 4 (primary endpoint) | 44% | 44% | P=0.939 |
| Endoscopic response, Week 12 (primary endpoint) | 43% | 39% | P=0.462 |
Four doses of 160 mg added nothing over the standard 160/80 mg start.
Source: D'Haens 2022, abstract. The week-56 comparison of clinically adjusted and TDM-guided maintenance is reported in the abstract only as similar, without numbers.
Structured abstract
BackgroundAdalimumab is often escalated when Crohn's disease responds incompletely, but whether more drug from the start, or maintenance dosing guided by drug levels, improves outcomes had not been established.
MethodsPhase 3, randomised, double-blind, multicentre trial with re-randomisation at week 12 for maintenance strategy. 514 patients. Primary endpoint: Co-primary: clinical remission at week 4 and endoscopic response at week 12.
ResultsPrimary result. Clinical remission at week 4: 44% vs 44% (P=0.939). Endoscopic response at week 12: 43% vs 39% (P=0.462). Higher induction was not superior.
Take-homeExtra-intensive adalimumab induction does not beat the standard 160/80 mg regimen, and proactive TDM-guided maintenance was no better than dosing adjusted to symptoms and CRP.
| Patients | 514 |
|---|---|
| Population | Adults with Crohn's Disease Activity Index 220–450, endoscopic evidence of mucosal inflammation, and previous failure of standard therapies. |
| Comparison | Higher vs standard adalimumab induction, then clinically adjusted vs TDM-guided maintenance |
| Drugs | adalimumab |
| Classes | Anti-TNF |
| Published | D'Haens GR, et al. Gastroenterology 2022;162:1876–90. |
Key points
- Higher induction: 160 mg at weeks 0, 1, 2 and 3 (n=308). Standard: 160 mg at week 0 and 80 mg at week 2 (n=206). Then 40 mg every other week; at week 12, re-randomised to clinically adjusted (CDAI and CRP; n=92) or TDM-guided (n=92) maintenance.
- Week 56 efficacy was similar with clinically adjusted and TDM-guided maintenance (exploratory endpoints).
- Safety profiles were comparable between induction regimens; no new safety concerns.
- Standard 160/80 mg induction remains appropriate; front-loading extra adalimumab added nothing.
Limitations
- Maintenance comparison was exploratory and small (92 per arm).
- Population had previously failed standard therapies; results may differ in early disease.
- Industry funded (AbbVie).
Commentary
SERENE-CD answered a common question from fellows: should a sick patient get a bigger adalimumab loading dose? The answer was no. It also did not show a benefit of proactive therapeutic drug monitoring in maintenance over clinically guided dosing in adults, in contrast with the paediatric PAILOT trial. Reactive drug-level testing at loss of response remains standard.
Journal club
Design
Phase 3, randomised, double-blind, multicentre trial with re-randomisation at week 12 for maintenance strategy. 514 patients.
Primary result. Clinical remission at week 4: 44% vs 44% (P=0.939). Endoscopic response at week 12: 43% vs 39% (P=0.462). Higher induction was not superior.
Validity and applicability
- Maintenance comparison was exploratory and small (92 per arm).
- Population had previously failed standard therapies; results may differ in early disease.
- Industry funded (AbbVie).
Where it sits now
Extra-intensive adalimumab induction does not beat the standard 160/80 mg regimen, and proactive TDM-guided maintenance was no better than dosing adjusted to symptoms and CRP.
- 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.
- REScUE (2026): After secondary loss of response to ustekinumab, IV reinduction plus every-4-week dosing is no better than reinduction plus every-8-week dosing, and few patients regain remission either way.
- LIBERTY-CD (2024): After IV infliximab induction, subcutaneous infliximab 120 mg every 2 weeks maintains remission and endoscopic response in Crohn's disease, an option for patients who prefer injections to infusions.
- VISIBLE 2 (2022): After two IV doses, vedolizumab 108 mg SC every 2 weeks maintains remission in Crohn's disease better than placebo, so patients can switch to home injections.
Questions for discussion
- Higher induction raised drug exposure but not remission. What does this say about the exposure–response link seen in observational drug-level studies?
- Both maintenance strategies could escalate. Why might TDM-guided dosing fail to beat clinically adjusted dosing when the comparator can also escalate?
- The co-primary endpoints were at weeks 4 and 12. Could a benefit of front-loading appear later, or only in a subgroup such as high inflammatory burden?