Gilles J. Hoilat, MBBS, Seren Durer, MD, Ceren Durer, MD, Divey Manocha, MD; SUNY Upstate Medical University, Syracuse, NY
Introduction: Patients with moderate to severe Ulcerative Colitis (UC) who are refractory or intolerant to standard treatment regimen such as tumor necrosis factor-α inhibitors or immunomodulators (azathioprine) are difficult to treat population. Novel therapeutic approaches are evolving to improve the outcomes of these patients. This review aims to summarize phase II/III trials using monoclonal antibodies (mAb) for the treatment of UC unresponsive to standard regimens. Methods: A comprehensive literature search was performed using PubMed, Embase, Web of Science and Clinicaltrials.gov for identification of late phase (II/III) trials of mAbs for UC treatment. FDA-approved mAbs were excluded. Studies were selected based on PRISMA guideline. Results: A total of 378 studies were identified and five studies (n=783 patients) met our inclusion criteria. Antibodies directed against IL-23 (mirikizumab), α4β7 and αEβ7 integrins (Etrolizumab), MAdCAM-1 (ontalimumab) were included. The results of clinical response, clinical remission and endoscopic remission are depicted in table 1. The Mayo and Partial Mayo scoring system defined by endoscopic score (ES), and patient-reported rectal bleeding (RB) and stool frequency (SF) was used.
Etrolizumab: In the EUCALYPTUS study, no patients in the placebo group had clinical remission at week 10, compared with 21% patients in the 100 mg group and 10% patients in the 300 mg plus loading dose (LD) group. Furthermore, no placebo group had endoscopic remission at week 10, compared to 10% in the 100 mg group and 8% patients in the 300 mg plus LD group. In the HICKORY Study, 50.8% of the patients receiving 105 mg had a clinical response; 12.3% achieved clinical remission and 23.9% achieved endoscopic remission at week 14. Ontamalimab: In TURANDOT study, clinical remission rates at week 12 were reported in 23.9% (7.5 mg group), 40.3% (22.5mg group), 36.6% (75 mg group), 25.7% (225 mg group) of patients. Mirikizumab: At week 12, 15.9%, 22.6%, and 11.5% of patients in the 50mg, 200mg, and 600mg groups achieved clinical remission, respectively, compared with 4.8% of patients who received placebo. Clinical responses occurred in 41.3%, 59.7%, and 49.2% of patients in the 50 mg, 200 mg, and 600 mg groups, respectively, compared with 20.6% of patients given placebo. Discussion: Novel mAbs for moderate to severe UC showed promising results. Further studies are required to explore the efficacy and safety of mAb. Ongoing studies for guselkumab, brazimumab, risankizumab are active.
Percentage of clinical Remission in patient taking Mirikizumab, Etrolizumab, and Ontamalimab
Disclosures: Gilles Hoilat indicated no relevant financial relationships. Seren Durer indicated no relevant financial relationships. Ceren Durer indicated no relevant financial relationships. Divey Manocha indicated no relevant financial relationships.