Introduction
Ozanimod (OZA) is approved in multiple countries for the treatment of moderately to severely active ulcerative colitis based on the results of the phase 3 True North (TN) clinical study. Previous data from the ongoing open-label extension (OLE) have demonstrated durability of efficacy in symptomatic, clinical, and mucosal endpoints for up to 3 years of continuous OZA treatment in patients who were clinical responders at TN Week (W) 52.
Aims & Methods
The present interim analysis of the TN OLE (data cutoff: 10 January 2022) explored whether the achievement of endpoints at TN W52, examined by increasing objectivity of the endpoint, would impact the durability of symptomatic and clinical outcomes with continuous OZA treatment up to OLE W94. OZA clinical responders at TN W52 who continued in the OLE were included in this analysis (n=131). These patients were categorized into subgroups based on the achieved endpoints of increasing objectivity (ie, clinical response, clinical remission, endoscopic improvement, complete endoscopic healing [endoscopy score = 0], histologic remission, mucosal healing, and stringent mucosal healing) at TN W52. The purpose was to determine whether these endpoints at TN W52/OLE baseline influence the proportion of patients maintaining symptomatic (ie, total/partial Mayo scores and symptomatic clinical response) and clinical (ie, clinical response, clinical remission, or corticosteroid [CS]–free remission) outcomes in the OLE. OLE outcomes were assessed up to OLE W94 using observed case (OC) and nonresponder imputation (NRI) analyses.
Results
Of the 131 patients included in this analysis, 114 (87%) completed OLE W46 and 94 (72%) completed OLE W94. Partial and total Mayo scores and symptomatic clinical responses (OC analysis) were similar and sustained over 94 wk of continuous OZA treatment during the OLE, regardless of the endpoint achieved at TN W52. Likewise, the maintenance of clinical response (OC analysis) at OLE W46 and OLE W94 was not impacted by the achievement of endpoints of increasing objectivity at TN W52 (Table). Achievement of clinical remission at TN W52 had an incremental benefit over clinical response at TN W52 for the maintenance of clinical remission and CS-free remission at OLE W94, but other endpoints of higher objectivity had no additional benefit (OC analysis) (Table). A similar pattern was observed for NRI analyses. Clinical outcomes were sustained from OLE W46 to OLE W94 regardless of the endpoint achieved at TN W52: clinical response: 71.4%–78.4%; clinical remission: 65.2%–70.0%; and CS-free remission: 63.6%–70.6%.
| Endpoints (increasing in objectivity) at TN W52 (OC analysis), % (n/N) | Clinical responsea | Clinical remissionb | CS-free remissionc |
| OLE W46 | OLE W94 | OLE W46 | OLE W94 | OLE W46 | OLE W94 |
| Clinical responsea (N=131) | 95.9 (93/97) | 91.4 (74/81) | 72.2 (70/97) | 69.1 (56/81) | 70.1 (68/97) | 67.9 (55/81) |
| Clinical remissionb (N=83) | 97.0 (64/66) | 94.4 (51/54) | 81.8 (54/66) | 75.9 (41/54) | 80.3 (53/66) | 74.1 (40/54) |
| Endoscopic improvement (MES ≤1; N=93) | 97.3 (73/75) | 95.2 (60/63) | 78.7 (59/75) | 73.0 (46/63) | 77.3 (58/75) | 71.4 (45/63) |
| Complete endoscopic healing (MES=0; N=50) | 97.6 (40/41) | 90.9 (30/33) | 82.9 (34/41) | 69.7 (23/33) | 80.5 (33/41) | 66.7 (22/33) |
| Histologic remission (Geboes index score <2.0; N=68) | 98.1 (51/52) | 95.3 (41/43) | 82.7 (43/52) | 74.4 (32/43) | 80.8 (42/52) | 72.1 (31/43) |
| Mucosal healing (MES ≤1 and Geboes index score <2.0; N=61) | 97.9 (46/47) | 94.7 (36/38) | 80.9 (38/47) | 71.1 (27/38) | 78.7 (37/47) | 68.4 (26/38) |
| Stringent mucosal healing (MES=0 and Geboes index score <2.0; N=37) | 96.6 (28/29) | 91.3 (21/23) | 79.3 (23/29) | 65.2 (15/23) | 75.9 (22/29) | 60.9 (14/23) |
Denominators for the OC analysis were based on the numbers of patients who completed OLE W46 or OLE W94 and had data available for the endpoints in question.
aClinical response: reduction from baseline in the 9-point Mayo score of ≥2 points and ≥35%, and a reduction from baseline in RBS of ≥1 point or an absolute RBS of ≤1 point. bClinical remission: RBS=0, SFS ≤1 point (and a decrease of ≥1 point from the baseline SFS), and endoscopy subscore ≤1 point. cCS-free remission: clinical remission while off CS for ≥12 wk.
MES, mucosal endoscopy subscore; RBS, rectal bleeding subscore; SFS, stool frequency subscore. |
Conclusion
Symptomatic response and clinical outcomes with OZA were durable up to W94 in the OLE. Maintenance of these long-term outcomes was not notably impacted by the achievement of increasingly more objective measures of responsiveness at W52 of TN.
Disclosure
This study was funded by Bristol Myers Squibb, Princeton, NJ, USA.
SD: received honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor.
RP: received consulting fees from Abbott, AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Therapeutics, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Schering-Plough, Shire, Sublimity Therapeutics, Theravance, UCB, and Takeda; received speaker fees from AbbVie, Arena, Celgene, Eli Lilly, Ferring, Gilead Sciences, Janssen, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda; received research/educational support from AbbVie, Ferring, Janssen, Pfizer, and Takeda; served on an advisory board for AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Sandoz, Shire, Sublimity Therapeutics, Takeda, and Theravance.
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.
DTR: received grant support from Takeda; consulted for AbbVie, AltruBio, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, 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 Therapeutics, Syneos, Takeda, Target RWE, and Trellus Health.
DM, HW, MTO, HA, and AJ: employees and/or shareholders of Bristol Myers Squibb.
MTA: consulted or participated in advisory board for AbbVie, Amgen, Arena, Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly, Gilead Sciences, Janssen, Microba Life Sciences, Pfizer, Prometheus Biosciences, UCB Biopharma, and WebMD Global; reported teaching, lecturing, or speaking for Alimentiv, Amgen, Janssen, and Takeda.
