Abstract Background We performed a systematic review and network meta-analysis to compare the short and long-term efficacy of thethree available JAK inhibitors (JAKi) (Tofacitinib/TOFA, filgotinib/FILGO, upadacitinib/UPA) in patients with moderate-to-severe UC. Methods We performed a systematic review and network meta-analysis (PRISMA guidelines) of randomized controlled trials led in adults, evaluating the efficacy of JAKi in moderate-to-severe UC. The outcome mesures were 1) steroid-free symptomatic remission (CFREM) after induction therapy (partial Mayo score ≤ 2), 2) clinical remission per modified Mayo score after induction therapy, 3) CFREM at one year among induction-responders, 4) CFREM at one year among patients in clinical remission after induction. The network meta-analysis was carried out according to a random effects model. The results are presented as relative risk (RR) with95% confidence interval. The SUCRA ranking method was used to rank the treatments. Results Nine studies were included in this network meta-analysis, including a total of 2015 patients.TOFA 10mg bid, FILGO 200 mg qd and UPA 45mg qd were more effective than placebo to induce CFREM and CFREM with endoscopicimprovement. Side-by-side comparisons between JAKi found a higher efficacy of UPA 45 mg qd versus FILGO 200 mg qd (RR = 0.220.10; 0.45) for induction but no other significant difference between JAKi. SUCRA ranking hierarchizes induction therapiesas following : UPA 45 mg qd (0.99), TOFA 10mg bid (0.75), FILGO 200 mg qd (0.27) and placebo (0.01). Among induction-responders, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd, FILGO 100 mg qd,UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with the following SUCRA ranking :UPA 30mg qd (0.85), TOFA 10mg bid (0.80), FILGO 200 mg qd (0.64), TOFA 5mg bid (0.56), UPA 15 mg (0.44), and placebo (0.01). Among patients in CFREM after induction phase, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd,FILGO 100 mg qd, UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with a differentranking (SUCRA) : TOFA 10 mg bid (0.84), FILGO 200 mg bid (0.74), TOFA (5mg bid) (0.66), UPA 30mg qd (0.63), UPA 15 mg (0.44) and placebo (0.09). Conclusion While this network meta-analysis confirms the efficacy of JAKi to induce and maintain CFREM in moderate-to-severe UC,UPA seems to be the most effective JAKi to induce and maintain CFREM. However, once CFREM achieved after induction, continuingthe same dose than during induction such as TOFA (10mg bid) or FILGO 200 mg seems to be more effective than reducing the dose (UPA 30 mg or UPA 15 mg) to maintain remission highlighting the dose-efficacy relationship of JAKi. Conflict of interest: Buisson, Anthony: Consulting fees from: Abbvie, AlfaSigma, Amgen, Arena, Biogen, Celltrion, CTMA, Ferring, Galapagos, Guty Care, Janssen, Hikma, Lilly, Mylan, Nexbiome, Pfizer, Roche, Takeda, Tillotts Lecture fees from: Abbvie, AlfaSigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Hikma, Janssen, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma Research fundings from: Abbvie, AlfaSigma, Celltrion, Janssen, Lessaffre, Lilly, Pfizer, Takeda Guilmoteau, Thomas: No conflict of interest Hupé, Marianne: No conflict of interest Pereira, Bruno: No conflict of interest
Buisson et al. (Thu,) studied this question.