Mirikizumab improves disease, symptom severity in patients with Crohn’s disease

Treatment with the anti-interleukin-23p19 inhibitor mirikizumab led to significant improvements in patient-assessed disease severity and activity, as well as abdominal pain, in individuals with moderate-to-severe active Crohn’s disease, according to phase II data presented at the Crohn’s and Colitis Congress (CCC) 2022.

During the 12-week induction phase, 191 participants (mean age 39 years, 49 percent male) were randomized 2:1:1:2 to receive either IV placebo or mirikizumab 200, 600, or 1,000 mg Q4W. The 40-week maintenance phase ensued thereafter, wherein participants on mirikizumab who have achieved ≥1 point improvement in the Simple Endoscopic Score for Crohn’s Disease (SES-CD) were randomized 1:1 to either continue with their IV induction regimen (IV-C arm) or transition to SC mirikizumab 300 mg Q4W (IV-SC arm). IV mirikizumab 1,000 mg Q4W was given to those who have not achieved endoscopic improvement or nonimprovers (NI-1,000 arm) and those who received placebo during the induction phase (PBO-1,000 arm).

Disease severity, activity

Compared with the placebo arm, all mirikizumab arms showed significantly greater reductions in disease severity, as reflected by the changes from baseline Patient’s Global Rating of Severity (PGRS) scores by week 12 (least square mean [LSM] changes, –1.0; p<0.05 [200 mg], –1.3; p<0.001 [600 mg], and –1.0; p<0.01 [1,000 mg]). [CCC 2022, abstract P040]

The drop in PGRS score was observed as early as week 4 among patients who were on mirikizumab 600 mg (LSM change, –0.44; p<0.05), which persisted throughout week 12, the researchers noted.

In terms of disease activity, mean Patient’s Global Rating of Change (PGRC) scores were lower in all mirikizumab arms (2.8, 2.6, and 2.5 for 200, 600, and 1,000 mg, respectively) compared with the placebo arm (3.6) during the induction phase.

From week 12 through 52, all mirikizumab recipients showed continued improvements in disease severity (mean changes from baseline PGRS score, –2.0, –1.8, –1.8, and –1.7 for IV-C, IV-SC, NI-1,000, and PBO-1,000 arms, respectively) and disease activity (mean PGRC scores, 2.1, 2.0, 1.7, and 1.7, respectively).

“[These findings imply that] all patients reported improvements in their symptoms with mirikizumab treatment. The improvements in disease … severity [and activity] were sustained or improved with continued maintenance treatment,” said the researchers.

Abdominal pain

Compared with those who were receiving placebo, those receiving mirikizumab 600 mg had a significant reduction in Abdominal Pain Numeric Reporting Scale (AP NRS) score at week 8 (LSM change, –1.01; p=0.02). A similar trend was observed across all mirikizumab arms at week 12 (LSM changes, –2.0; p<0.05 [200 mg], –2.3; p<0.01 [600 mg], and –1.9; p<0.05 [1,000 mg]). [CCC 2022, abstract P041]

In terms of observed changes from baseline AP NRS scores, week 52 saw continued improvements in the NI-1,000 arm (–3.1), more so in the PBO-1,000, IV-C, and IV-SC arms (–3.9, –3.7, and –4.0, respectively).

These results imply that treatment with mirikizumab led to improvements in abdominal pain, the researchers said.

Taken together, these findings reinforce the results of other phase II studies on mirikizumab for CD, psoriasis, and ulcerative colitis. [UEGW 2019; abstract OP166; Br J Dermatol 2019;181:88-95; Gastroenterology 2020;158:537-549]