Introduction
The favorable pharmacokinetic profile of the subcutaneous formulation of infliximab (SQ IFX) could challenge the dogma of systematic combination therapy when using IFX therapy, as recommended with its intravenous route.
Aims & Methods
We aimed to demonstrate the non-inferiority of subcutaneous infliximab monotherapy (SQ IFX mono) compared with combination therapy (SQ IFX + IS) in patients with ulcerative colitis (UC).
In this multicenter (15 centers) retrospective study, we consecutively included all patients ≥18 years-old with symptomatic UC (partial Mayo score >2) who started SC infliximab 120 mg every 2 weeks, from week 6 or W10 after an IV induction regimen (2 or 3 IV infusions at 5 mg/kg at week 0, W2 ± W6). Acute severe colitis were excluded.
The primary endpoint was symptomatic remission (partial Mayo score ≤2) without steroid (CFREM) and is expressed as % of months (4-week periods) spent in CFREM (month being the statistical unit). The non-inferiority margin was predefined at -10% according to IOIBD recommendations. A priori sample-size calculation (considering hypothesis of 55% of months spent in CFREM in reference group, 90% power, one-sided 95% confidence interval due to non-inferiority design, and imbalance between groups), indicated that 2,160 months were required, i.e 210 patients. We present here the results of an interim analysis while data from half of participating centers have been collected.
Secondary endpoints (CFREM at W12, W24 and W52) and long-term outcomes (time to IFX discontinuation, to hospitalization or to colectomy) considered the patient as the statistical unit.
All comparisons were performed using propensity-score adjustment (IPTW) adjusted on age, UC duration, concomitant steroids, UC severity, prior exposure to advanced therapy.
Results
To date, 117 patients (1,137months) have been included (SQ IFX mono = 32 and SQ IFX +IS = 85 patients). The two groups were comparable except for higher rate of bio-naïve patients in SQ IFX mono (54.0% vs 33.0%, P=0.01).
Considering 1,137 months for the analysis, the percentage of months spent in CFREM within the first year (primary endpoint) was not inferior in patients treated with SQ IFX mono (65.0%) compared to those receiving SQ IFX combo (67.5%) (- 2.5% [ -7.9%; + 2.8%]; confidence interval not crossing the non-inferiority margin of -10%).
After IPTW (N = 117 patients), no difference of CFREM at W12 (69.8% vs 69.8%; p=1.0), W24 (79.4% vs 72.7%; p=0.43), and W52 (81.0% vs 73.9%; p=0.41) was seen between SQ IFX mono and SC IFX + IS, respectively, with no difference in subgroups such as bio-exposed, E3 phenotype, and prior exposure to IS.
After IPTW (N = 117 patients), long-term outcomes such as IFX discontinuation (HR = 0.94 [0.14-2.10], p = 0.88), hospitalization (HR = 0.74 [0.18-3.03], p = 0.68) and colectomy (none in the two groups) were not different between SQ IFX mono vs combo.
Digestive intolerance (6 patients, 7.0%) and haemato-toxicity (one patients, 1.2%) were observed only in combo group. No other significant difference regarding safety was observed between the two groups.
Conclusion
In this real-world multicenter study, SQ infliximab monotherapy appeared non-inferior to combination therapy in UC with no difference of effectiveness at both short and long-terms.
Disclosure
•Consulting fees from:Abbvie, Amgen, Arena, Biogen, Celltrion Healthcare, Ferring, Galapagos/AlfaSigma, GutuCare/Resilience, Hikma, J&J, Lilly, Mylan, Nexbiome, Pileje, Pfizer, Roche, Sandoz, Takeda, Tillotts
•Lecturer for Abbvie, Amgen, Biogen, Celltrion Healthcare, Ferring, Fresnius-Kabi, Galapagos/Alfa Sigma, Hikma, J&J, Lilly, Mayoli-Spindler, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor-Pharma
•Research fundings from Abbvie, Celltrion Healthcare, Galapagos/AlfaSigma, J&J, Lessaffre, Lilly, Pfizer, ScientaLab,Takeda.
REMONO-UC was an investigator-initiated study supported by Celltrion.
