Introduction
While three JAK inhibitors are now available in Ulcerative Colitis (UC), the hierarchy of these treatments according to their effectiveness, remains to be determined.
Aims & Methods
In the JAKARTA study, we aimed to compare the effectiveness of the three available JAK inhibitors (tofacitinib/TOFA, filgotinib/FILGO and upadacitinib/UPA) in bio-exposed patients with UC.
In this retrospective multicenter study (12 centres), we included all consecutive patients with UC ≥18 years-old, partial Mayo score > 2 who had started TOFA, FILGO or UPA after receiving ≥ 1 biologic between JAN2019 and JUN2022. Acute severe UC were excluded.
Following regimen were applied for TOFA (10mg b.i.d until W8 and 5mg or 10 mg b.i.d according to physician’s judgement), FILGO (200mg q.d) and UPA (45mg q.d until W8 and 45mg, 30 mg or 15 mg q.d according to physician’s judgement).
The primary endpoint was symptomatic remission (partial Mayo score ≤ 2) without corticosteroids (CFREM) at W16. Secondary endpoints were clinical and endoscopic remission (CFREM + endoscopic Mayo score ≤ 1), histological and endoscopic mucosal improvement (HEMI) (= clinical-endoscopic and histological remission (Nancy index ≤ 1)), drug retention (treatment discontinuation-free survival using Kaplan-Meier curve), time to colectomy, time to UC-related hospitalization and secondary loss of response among patients in CFREM at W16.
All the comparisons were performed using propensity scores adjustment (IPTW).
Results
A total of 290 patients were included: 150, 79 and 61 in TOFA, FILGO, and UPA arms, respectively. The 3 groups were comparable except for higher proportion of patients with previous exposure to > 3 biologics in UPA group (p < 0.001). TOFA 10 mg b.i.d was continued until W16 in 47.0% of patients. FILGO was maintained at 200 mg in 97.5%. UPA was diminished at 30 mg and 15 mg at W8 in 55.6% and 3.3% of patients, respectively.
After IPTW, CFREM at W16 was higher in UPA (60.1%) compared to TOFA (38.9%) or FILGO groups (36.0%) (p = 0.026 and 0.016, respectively). No predictive factor of efficacy/ failure was identified with these 3 JAK inhibitors.
We failed to show any significant difference regarding clinical-endoscopic remission (UPA:16.5%, TOFA:16.5%, FILGO:12.8%) or HEMI (UPA:11.9%, TOFA: 4.4, FILGO: 12.7%) at W16.
Among patients who reduced the dose to the recommended maintenance regimen (TOFA 5 mg b.i.d and UPA 30 or 15 mg q.d) between W8 and W16, the need for dose re-escalation to the induction dose was 33.8% (27/80) for TOFA, 14.7% (5/34) for UPA30mg and 50.0 % (1/2) for UPA 15 mg. After adjustment, drug retention was longer for UPA compared to TOFA (HR = 0.38 [0.17-0.85], p = 0.019) and FILGO groups (HR = 0.17 [0.08-0.65], p < 0.001) and shorter in FILGO than in TOFA group (HR = 1.57[1.02-2.41], p = 0.038).
No difference was demonstrated in terms of time to hospitalization or surgery between the 3 groups.
Among patients achieving CFREM at W16 (regardless of the dose), secondary loss of response (symptomatic relapse) was similar for TOFA:12.8% (N=47 patients), FILGO: 19.2% (N = 26 patients) and UPA: 10.3% (N = 29 patients) (p=ns after IPTW).
Conclusion
In this real-world evidence multicenter study, UPA was the most effective JAK inhibitor in UC at short and long-term but the large use of off-label maintenance doses in current practice needs further safety investigations.
Disclosure
Consulting fees from: Abbvie, Amgen, Arena, Biocon, Biogen, Celltrion Healthcare, CTMA, Ferring, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pfizer, Roche, Sandoz, Takeda et Tillotts
Lecture fees from : Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Ferring, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma
Research grants/fundings from: Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda
