Introduction
Ozanimod (OZA) is approved for the treatment of moderately to severely active (mod/sev) ulcerative colitis (UC). OZA demonstrated superior efficacy vs placebo in the 52-wk phase 3 True North (TN) study in adults with mod/sev UC and demonstrated durable efficacy over ~3 years of continuous treatment in the open-label extension (OLE). Previous analyses reported greater clinical and mucosal efficacy during TN in patients (pts) who were biologic-naive vs biologic-experienced.
Aims & Methods
The goal of the present analysis was to evaluate the effect of prior biologic exposure on the durability of OZA efficacy in pts with mod/sev UC. Pts who achieved clinical response with or without remission after 52 wk of continuous OZA treatment during TN and entered the OLE were evaluated (data cutoff: 10 January 2022). Symptomatic clinical response and remission were evaluated through OLE W94, and clinical response, clinical remission, endoscopic improvement, and corticosteroid (CS)–free remission were evaluated at OLE W46 and W94 using observed case (OC) and nonresponder imputation (NRI) analyses. Data were analyzed in pts with and without prior biologic exposure at baseline. Pts exposed to only a Janus kinase inhibitor were not included in this analysis.
Results
In all, 128 pts with prior biologic information entered the OLE after achieving clinical response on continued OZA at TN Week (W) 52 (biologic-naive, n=82; biologic-experienced, n=46). Baseline pt characteristics in TN were generally balanced between both groups, except for longer disease duration, higher CS use at screening, and higher prior immunomodulator use in biologic-experienced pts. Complete and partial Mayo scores were higher in biologic-experienced pts at OLE entry. The proportions of pts with symptomatic response at OLE W5 were 100% (OC) in both biologic-naive and -experienced pts. At OLE W5, 90.8% (OC) of biologic-naive pts and 72.1% (OC) of biologic-experienced pts achieved symptomatic remission. Rates of symptomatic clinical response and clinical remission (OC) were maintained through OLE W94. In pts with clinical response with or without remission at TN W52, the proportions of biologic-naive and -experienced pts achieving clinical response, clinical remission, endoscopic improvement, and CS-free remission at OLE W46 and W94 are shown in the Table. Overall, greater efficacy was observed in biologic-naive vs -experienced pts across all endpoints. Notably, pts in clinical remission at TN W52 showed similar efficacy rates in both biologic-naive and -experienced pts, whereas biologic-naive pts demonstrated greater efficacy than biologic-experienced pts in those without clinical remission at TN W52. Similar patterns were seen using NRI analysis.
| Efficacy at OLE W46 and OLE W94 by biologic exposure at baseline and clinical response at W52/OLE entry (OC analysis) | Biologic-naïve (n=82)
Clinical response at TN W52a | Biologic-experienced (n=46)
Clinical response at TN W52a | Biologic-naive (n=58)
Clinical remission at TN W52b | Biologic-experienced (n=22)
Clinical remission at TN W52b | Biologic-naive (n=24)
Clinical response (without remission) at TN W52c | Biologic-experienced (n=24)
Clinical response (without remission) at TN W52c |
Clinical response,a % (n/N) | OLE W46 | 95.2 (60/63) | 96.8 (30/31) | 95.7 (44/46) | 100.0 (17/17) | 94.1 (16/17) | 92.9 (13/14) |
| OLE W94 | 90.9 (50/55) | 92.0 (23/25) | 95.0 (38/40) | 92.3 (12/13) | 80.0 (12/15) | 91.7 (11/12) |
Clinical remission,b % (n/N) | OLE W46 | 77.8 (49/63) | 61.3 (19/31) | 82.6 (38/46) | 82.4 (14/17) | 64.7 (11/17) | 35.7 (5/14) |
| OLE W94 | 70.9 (39/55) | 64.0 (16/25) | 77.5 (31/40) | 69.2 (9/13) | 53.3 (8/15) | 58.3 (7/12) |
Endoscopic improvement,d % (n/N) | OLE W46 | 82.6 (57/69) | 68.8 (22/32) | 86.3 (44/51) | 88.9 (16/18) | 72.2 (13/18) | 42.9 (6/14) |
| OLE W94 | 73.7 (42/57) | 71.4 (20/28) | 78.0 (32/41) | 78.6 (11/14) | 62.5 (10/16) | 64.3 (9/14) |
CS-free remission,e % (n/N) | OLE W46 | 74.6 (47/63) | 61.3 (19/31) | 80.4 (37/46) | 82.4 (14/17) | 58.8 (10/17) | 35.7 (5/14) |
| OLE W94 | 69.1 (38/55) | 64.0 (16/25) | 75.0 (30/40) | 69.2 (9/13) | 53.3 (8/15) | 58.3 (7/12) |
aClinical response: decrease from baseline in the 3-component Mayo score (sum of RBS, SFS, and MES) of ≥2 points and ≥35% and reduction of ≥1 point in RBS or an absolute RBS of ≤1 point. bClinical remission: RBS=0, SFS ≤1 point (and a decrease of ≥1 point from baseline SFS), and MES ≤1. cMet criteria for clinical response but not clinical remission. dEndoscopic improvement: MES ≤1 point. eClinical remission while off CS for ≥12 wk. MES, Mayo endoscopy subscore; RBS, rectal bleeding subscore; SFS, stool frequency subscore. |
Conclusion
Clinical and symptomatic outcomes were maintained in biologic-naive and -experienced pts with mod/sev active UC receiving ~3 years of continuous OZA treatment. Greater efficacy was generally observed in biologic-naive pts; however, biologic-naive and -experienced pts who achieved clinical response with remission at TN W52 had similar efficacy during the OLE.
Disclosure
The study was funded by Bristol Myers Squibb, Princeton, NJ, USA.
SV: received research funding from AbbVie, Galapagos, Johnson & Johnson, Pfizer, and Takeda; received consulting and/or speaking fees from AbbVie, Abivax, AbolerIS, AgomAb, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Eli Lilly, Falk Pharma, Ferring, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Hospira, IMIDomics, Janssen, Johnson & Johnson, Materia Prima, MiroBio, Morphic Therapeutic, MRM Health, MSD, Mundipharma, Pfizer, ProDigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts Pharma AG, and Zealand.
AA: consulted for AbbVie, Bristol Myers Squibb, DiaSorin, Eli Lilly, Gilead, Janssen, Pfizer, Takeda, and TLL Pharmaceuticals; received speaker fees from AbbVie, Bristol Myers Squibb, Janssen, Pfizer, and Takeda.
DCW: received honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Arena, Celgene/Bristol Myers Squibb, Janssen, Pfizer, Prometheus, Takeda, and UCB.
MR: served on advisory boards and consulted for AbbVie, Alfasigma, Allergan, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Gilead, Janssen, Miraca Labs, Pfizer, Prometheus, Seres, Salix, Takeda, Target RWE, and UCB.
DM, HW, and AJ: employees and/or shareholders of Bristol Myers Squibb.
JFC: received research grants from AbbVie, Janssen, and Takeda; received payment for lectures from AbbVie, Allergan, Amgen, Bristol Myers Squibb, Ferring, Shire, and Takeda; received consulting fees from AbbVie, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Enterome, Ferring, Genentech, Gilead, Iterative Scopes, Ipsen, Immunic, Imtbio, Inotrem, Janssen, Landos, LimmaTech Biologics AG, Medimmune, Merck, Novartis, O Mass, Otsuka, Pfizer, Shire, Takeda, TiGenix, and Viela Bio; holds stock options in Intestinal Biotech Development.