Introduction
Many patients (pts) with ulcerative colitis (UC) do not achieve long-term remission with conventional therapies but are hesitant to switch to advanced therapies. Ozanimod (OZA) is an oral advanced therapy approved for the treatment of moderately to severely active UC. Durability of up to 3 years of continuous OZA treatment has been reported in the True North (TN) open-label extension (OLE).
Aims & Methods
The objective of the current analysis of the TN OLE was to assess the long-term durability of OZA treatment in pts who were inadequately controlled on conventional therapies at TN baseline. Advanced therapy–naive pts who were OZA clinical responders at TN Week 52 were grouped by baseline endoscopic disease activity as moderate (Mayo endoscopy subscore [MES]=2) or severe (MES=3). OZA efficacy (clinical remission, clinical response, corticosteroid (CS)-free remission, and endoscopic improvement) was evaluated at OLE W46 and OLE W94. Symptomatic clinical response (decrease from baseline in the combined 6-point rectal bleeding subscore [RBS] + stool frequency subscore [SFS] of ≥1 point and ≥30% and a decrease of ≥1 point in RBS or absolute RBS ≤1 point) and symptomatic clinical remission (RBS=0 and SFS ≤1 point [and decrease of ≥1 point from baseline SFS]) were assessed from OLE W5 to W94. All endpoints were assessed using observed case (OC) and nonresponder imputation (NRI) analyses.
Results
Of the 82 advanced therapy–naive pts who entered the OLE in clinical response after 52 wk of OZA treatment during TN, 45 had moderate baseline endoscopic disease and 37 had severe baseline endoscopic disease. Baseline demographic and clinical characteristics were generally similar across groups. Based on OC analysis, symptomatic clinical response and remission were observed in 100.0% and 90.5% of moderate pts, respectively, at OLE W5 and in 100.0% and 91.2% of severe pts, respectively, at OLE W5. Rates of symptomatic clinical response and remission were maintained through OLE W94. Rates of clinical remission, clinical response, CS-free remission, and endoscopic improvement at OLE W46 were similar in moderate and severe pts and were maintained through OLE W94 in the OC analysis (Table). Overall, the data followed similar patterns in the NRI analyses across endpoints.
| Efficacy during the OLE by baseline endoscopic disease activity in advanced therapy–naive pts who entered the OLE in clinical response after 52 wk of OZA treatment during TN (OC analysis) |
| Moderate disease (MES=2)
(n=45) | Severe disease (MES=3)
(n=37) |
| OLE W46 | OLE W94 | OLE W46 | OLE W94 |
Clinical
remission,a n (%) | 28/36 (77.8) | 19/29 (65.5) | 21/27 (77.8) | 20/26 (76.9) |
Clinical
response,b n (%) | 34/36 (94.4) | 24/29 (82.8) | 26/27 (96.3) | 26/26 (100) |
| CS-free remission,c n (%) | 26/36 (72.2) | 18/29 (62.1) | 21/27 (77.8) | 20/26 (76.9) |
| Endoscopic improvement,d n (%) | 35/39 (89.7) | 21/30 (70.0) | 22/30 (73.3) | 21/27 (77.8) |
| aClinical remission: RBS=0, SFS ≤1 point (and a decrease of ≥1 point from baseline SFS), and MES ≤1 point. bClinical response: decrease from baseline in the 3-component Mayo score (sum of RBS, SFS, and MES) of ≥2 points and ≥35% and a reduction of ≥1 point in RBS or absolute RBS of ≤1 point. cClinical remission at W52 while off CS for ≥12 wk. dEndoscopic improvement: MES ≤1 point. |
Conclusion
Advanced therapy–naive pts who experienced disease progression on conventional therapies had sustained efficacy on OZA for up to 3 years. Baseline endoscopic disease activity did not affect the long-term durability of OZA responders. OZA may be an appropriate advanced therapeutic option for sustaining long-term symptomatic and clinical benefit in pts with UC after loss of response to conventional treatments.
Disclosure
This study was funded by Bristol Myers Squibb, Princeton, NJ, USA.
LPB: served as a speaker, consultant, and advisory board member for AbbVie, Amgen, Biogaran, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Ferring, Forward Pharma, Genentech, H.A.C. Pharma, Hospira/Pfizer, InDex Pharmaceuticals, Janssen, Lycera, Merck, Mitsubishi, Norgine, Samsung Bioepis, Sandoz, Takeda, Theravance, Tillotts, and Vifor.
MDL: received research funding from Pfizer and Takeda; consulted for AbbVie, Bristol Myers Squibb, Calibr, Eli Lilly, Genentech, Janssen, Pfizer, Prometheus, Roche, Salix, Takeda, Target RWE, and Theravance.
BS: consulted for AbbVie, Arena, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Falk Pharma, Galapagos, Janssen, Pfizer, Prometheus, and Takeda; received speaker fees from AbbVie, CED Service GmbH, Falk Pharma, Ferring, Janssen, Novartis, Pfizer, and Takeda.
PI: received lecture fees from AbbVie, Bristol Myers Squibb, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Gilead, Janssen, MSD, Pfizer, Sandoz, Sapphire Medical, Shire, Takeda, Tillotts, and Warner Chilcott; received financial support for research from Celltrion, MSD, Pfizer, and Takeda; received advisory fees from AbbVie, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Hospira, Janssen, MSD, Pfizer, Pharmacosmos, Prometheus Biosciences, Roche, Samsung Bioepis, Sandoz, Takeda, Topivert, VH2, Vifor, and Warner Chilcott.
FC: received research support from Takeda; consulted for Arena, Celgene, GlaxoSmithKline, and Takeda.
AJ, HW, and MTO: employees and/or shareholders of Bristol Myers Squibb.
DTR: received grant support from Takeda; consulted for AbbVie, AltruBio, Aslan, Athos, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chronicles, ClostraBio, Connect BioPharma, EcoR1, Eli Lilly, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen, Kaleido Biosciences, Pfizer, Prometheus Biosciences, Reistone, Seres, Syneos, Takeda, Target RWE, and Trellus Health.
BA: received research funding from Takeda; consulted for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Medtronic, Pfizer, Samsung Bioepis, and Takeda; lectured for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, and Takeda.
