Mirikizumab in Crohn’s: Two-year data suggest continued benefit

Long-term treatment with mirikizumab, a monoclonal antibody targeting the interleukin-23 p19 subunit (IL-23p19), was associated with sustained improvements across multiple therapeutic targets through two years in patients with moderately to severely active Crohn’s disease. Some patients achieved these outcomes during the second year of therapy, according to interim results from the VIVID-2 extension study in press for Clinical Gastroenterology and Hepatology

"These findings suggest that treatment with mirikizumab can offer durable disease control," said lead author Bruce E. Sands, MD, MS, in an interview with GI & Hepatology News.  "Given the safety of mirikizumab and other anti–IL-23p19 antibodies, there is considerable interest in using these agents earlier in the treatment paradigm, including in newly diagnosed patients."

The results extend findings from the VIVID-1 trial, which demonstrated efficacy and safety through 52 weeks. VIVID-2 reports outcomes after an additional year, representing a total of 104 weeks of continuous therapy. Safety findings during the second year appeared consistent with the known safety profile of mirikizumab. 

About VIVID-2

VIVID-2 enrolled patients who completed VIVID-1. They had moderately to severely active Crohn’s disease and had experienced inadequate response, loss of response, or intolerance to conventional or approved biologic therapies.

Among 630 patients who received mirikizumab in VIVID-1 (900 mg intravenously at weeks 0, 4, and 8, followed by 300 mg subcutaneously every 4 weeks through week 52), 572 entered the extension study. A total of 465 patients were included in the safety population and 430 met criteria for the efficacy population, noted Dr. Sands, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues.

Patients who achieved endoscopic response at week 52 of VIVID-1 (n = 251) continued subcutaneous mirikizumab. Those without endoscopic response (n = 179) underwent reinduction with intravenous mirikizumab before returning to maintenance dosing.

Efficacy

At week 104, endoscopic response was achieved in 60.5% of patients using modified nonresponder imputation (67.1% observed case [OC]), and endoscopic remission occurred in 37.9% (41.7% OC). Clinical remission by Crohn’s Disease Activity Index (CDAI) occurred in 73.4% (80.9% OC).

Among patients who had achieved endoscopic response at week 52, most maintained these outcomes through 104 weeks. Endoscopic response was maintained in 81.8% (87.6% OC) of patients, endoscopic remission in 72.5% (78.6% OC), and CDAI remission in 86.9% (92.9% OC). Among week-52 responders who had not yet achieved endoscopic or CDAI remission, 33.3% (35.4% OC) and 55.8% (60.8% OC), respectively, gained those outcomes by week 104.

The corresponding rates of achieving these endpoints were 30.9%, 14.2%, and 65.7% (36.1%, 16.0%, and 75.4% OC), respectively, among week-52 nonresponders.

"Endoscopic healing is a major target that may limit the risk of bowel damage progression and improve long-term outcomes," noted the researchers. Repeat intravenous induction "may be a relevant option in some patients ... thereby avoiding the need to change treatment if endoscopic healing is not achieved."

Nearly all patients who received corticosteroids at baseline (94.3%) were corticosteroid-free at week 104.

Biomarkers and symptoms

During the first year of VIVID-2, median C-reactive protein (CRP) remained below 5 mg/L and fecal calprotectin (FCP) below 250 µg/g. The proportion achieving normalization was found to remain stable or increase between weeks 52 and 104.

Endoscopic outcomes at week 104 were most frequently observed with both CRP and FCP normalization at week 64, although rates were similar with FCP normalization alone. The researchers thus noted that biomarker normalization, "especially FCP, may be a reliable predictor of long-term endoscopic response and remission."

Mirikizumab showed sustained efficacy for bowel urgency outcomes, a symptom the researchers described as "under recognized and debilitating," with additional improvements during the second year of treatment.

Safety

During the second year of treatment, 64.7% of patients experienced treatment-emergent adverse events — most mild or moderate — and 7.7% had serious adverse events.

The most common adverse events were COVID-19 and upper respiratory infections. Adverse events led to treatment discontinuation in 2.6% of patients. One death due to COVID-19 pneumonia occurred in an unvaccinated patient.

Insights and opportunities

The researchers noted that the study used a treat-through design that did not restrict analyses to induction responders from VIVID-1, aligning with clinical practice and aiming to better understand long-term treatment effects, including among initial nonresponders.

Mirikizumab "showed sustained clinical and endoscopic remission in patients with moderately to severely active Crohn’s disease over two years, including among patients who had failed other biologic agents," Dr. Sands said. Patients who had achieved clinical remission at one year "did particularly well," with 92.9% maintaining clinical remission and 87.6% achieving endoscopic response at the end of two years. Mirikizumab also had "an excellent safety profile."

However, the researchers noted several limitations. VIVID-2 is an open-label study without a comparator group, which could influence reporting of outcomes. In addition, most participants were Asian or White, which may limit generalizability to other populations.

Looking ahead, Dr. Sands noted that "as mirikizumab is more widely used, real-world evidence should continue to evaluate the efficacy and safety in broader populations."

The study was funded by Eli Lilly and Company. Investigators reported multiple industry relationships, including with Eli Lilly.