Introduction:
As head-to-head comparisons of Janus kinase (JAK) inhibitors in ulcerative colitis (UC) are unavailable, their effectiveness was assessed in bio-exposed UC patients receiving tofacitinib (TOFA), filgotinib (FILGO), or upadacitinib (UPA). The aim was to evaluate short- and long-term outcomes in real-world clinical settings.
Patients and Methods:
A retrospective multicenter analysis was performed on UC patients (≥18 years) with partial Mayo score >2 who had received at least one prior biologic and started TOFA, FILGO, or UPA.
Following regimen were applied for TOFA (10mg b.i.d at W8: 5mg or 10 mg b.i.d according to physician's judgement), FILGO (200mg q.d) and for UPA (45mg q.d at W8: 45mg, 30 mg or 15 mg q.d according to physician's judgement).
The primary endpoint was corticosteroid-free symptomatic remission (CFREM) at week 16. Secondary outcomes included clinical-endoscopic remission, histological-endoscopic mucosal improvement (HEMI), and drug retention. Propensity score weighting (IPTW) was applied for comparative analysis.
Results:
|
Parameter |
TOFA (n=150) |
FILGO (n=79) |
UPA (n=61) |
|
CFREM at Week 16 (%) |
38.9% |
36.8% |
60.1% |
|
Clinical-Endoscopic Remission (%) |
16.5% |
12.8% |
16.5% |
|
HEMI (%) |
4.4% |
12.7% |
11.9% |
|
Dose Maintenance Failure (%) |
58.1% |
42.3% |
30.5% |
|
Secondary Loss of Response (%) |
12.8% |
19.2% |
10.3% |
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After adjustment, drug retention was longer for UPA compared to TOFA and FILGO groups (HR = 0.42 [0.21-0.85], p = 0.016) and shorter in FILGO than in TOFA group (HR = 1.60[1.07-2.38], p = 0.021). No difference was demonstrated in terms of time to hospitalization or surgery between the 3 groups.
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UPA demonstrated the highest CFREM at week 16 (p < 0.001).
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No significant differences were observed for endoscopic or histological outcomes.
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UPA had superior long-term retention; FILGO showed shorter retention than TOFA.
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No predictors of treatment response or failure were identified across the three drugs.
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Hospitalization and surgery rates were similar across groups.
Conclusion:
Among bio-exposed UC patients, upadacitinib was found to be more effective in achieving short-term remission and maintaining long-term treatment compared to tofacitinib and filgotinib. Despite promising results, the widespread off-label dosing of JAK inhibitors underscores the need for further safety evaluations.
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