Efficacy of Nirmatrelvir/Ritonavir (Paxlovid) for COVID-19 in Vaccinated Patients With Inflammatory Bowel Disease
Inas Mikhail, Aakash Desai, Sheena Crosby, Jana G Hashash, Mary Hayney, Freddy Caldera, Gursimran Kochhar, Francis A A Farraye
Background: Obefazimod (Obe) is an oral, once-daily (od) small molecule that enhances expression of microRNA-124 and is in phase 3 trials for moderately to severely active ulcerative colitis (UC). Obe showed efficacy and safety at week 8 in a placebo-controlled Phase 2b induction trial and a subsequent open-label maintenance (OLM) study. This post hoc analysis reports corticosteroid (CS)-free efficacy and safety at weeks 48 and 96 in patients receiving concomitant CS at induction baseline. Methods: In the Phase 2b induction trial, patients received placebo or Obe (25 mg, 50 mg, or 100 mg od) and could enter the optional 96-week OLM study with Obe 50 mg, regardless of clinical response. Patients were monitored monthly for safety and efficacy. At induction trial entry, patients could use concomitant CS if on a stable dose for $2 weeks before screening. CS tapering was recommended but not required at the OLM study baseline. CS-free status was defined as CS withdrawal $12 weeks before assessment. CS-free outcomes, including clinical remission (CR), endoscopic improvement (EI), and endoscopic remission (ER), were evaluated at weeks 48 and 96, along with safety. Results: At induction baseline, 115 patients (out of 252, 46%) received CS. Among patients with CS at induction baseline, CR rates were 56% at week 48 and 52% at week 96. CS-free CR was attained by 37% (43/115) at week 48 and 35% at week 96 within the same cohort. Among the 21 patients that were in CR but did not meet the definition of CS-free at week 48, the Principal Investigator (PI) did not attempt the optional CS tapering for 13 pts. An additional 4 patients were CS free, but for less than 12 weeks before the week 48 endpoint. Among the 20 patients that were in CR but did not meet the definition of CS-free at week 96, the PI did not attempt the optional CS tapering for 8 patients. An additional 7 patients were CS free, but for less than 12 weeks before the week 96 endpoint. EI was achieved by 64% at week 48 and 58% at week 96, with CS-free EI achieved by 44% of patients at week 48 and 39% at week 96. ER was achieved by 33% at week 48 and 31% at week 96, with CS-free ER achieved by 24% of patients at week 48 and 21% at week 96. Among patients with CS at induction baseline, 50% and 39% of patients had FCP , 150 mg/g at weeks 48 and 96, respectively. CS-free patients with FCP , 150 mg/g were 32% at week 48 and 28% at week 96. Overall, the safety profile within this cohort was consistent with the overall study population. Conclusions: Among patients receiving concomitant CS at induction baseline, meaningful proportions achieved CR, EI, and ER at weeks 48 and 96 in the OLM. Notably, a substantial proportion of patients met CS-free efficacy endpoints despite optional CS tapering. Concomitant CS use at induction baseline had no notable effect on the safety profile of Obe.
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