Clinical Studies of Anti-interleukin Therapies for Inflammatory Bowel Disease
| Drug | Target | Study | Disease | Number of patients | Key results |
|---|---|---|---|---|---|
| Ustekinumab | IL-12/23 p40 subunit | UNITI-110 | CD | 741 | *Response at week 6 - UST 130 mg IV 34.3%, UST 6 mg/kg IV 33.7%, PBO 21.5% (both p≤0.003) |
| UNITI-210 | CD | 628 | *Response at week 6 - UST 130 mg IV 51.7%, UST 6 mg/kg IV 55.5%, PBO 28.7% (both p<0.001) |
||
| IM-UNITI95 | CD | 567 | *Intention-to-treat analysis - 38.0% of the q12w group and 43.0% of the q8w group were in remission at week 152 *Original randomised groups - 61.9% of the q12w group and 69.5% of the q8w group were in remission at week 152 *All ustekinumab-treated patients (randomised and non-randomised) entering the long-term extension - 56.3% of the q12w group and 55.1% of the q8w group were in remission at week 152 |
||
| UNIFI9 | UC | 961 | *Clinical remission rate at week 8 (8 weeks induction) - UST 130 mg IV 15.6%, UST 6 mg/kg IV 15.5%, PBO 5.3% (both p<0.001) *Clinical remission rate at week 44 (44 weeks maintenance) - 90 mg SC q12w 38.4% (p=0.002), 90 mg SC q8w 43.8% (p<0.001), PBO 24.0% |
||
| Risankizumab | IL-23p19 subunit | NCT02031276121 | CD | 121 | *Clinical remission rate at week 12 - RZB 31%, PBO 15% (p=0.0489) |
| ADVANCE123 | CD | 931 | *Both RZB 600 mg and RZB 1,200 mg showed efficacy in clinical remission and endoscopic response at week 12 (p≤0.0001) *Clinical remission rates: 45% for RZB 600 mg and 42% for RZB 1,200 mg, compared to 25% for PBO |
||
| MOTIVATE123 | CD | 618 | *Both RZB 600 mg and RZB 1,200 mg showed efficacy in clinical remission and endoscopic response at week 12 (p≤0.0001) *Clinical remission rates: 42% for RZB 600 mg, 40% for RZB 1,200 mg, compared to 20% for PBO |
||
| FORTIFY124 | CD | 542 | *Clinical remission rate at week 52 - RZB 360 mg 52% (p=0.0054), RZB 180 mg 55% (p=0.0031), both higher than PBO 41% *Endoscopic response rate at week 52 - RZB 360 mg 47% (p<0.0001), RZB 180 mg 47% (p<0.0001), both higher than PBO 22% |
||
| INSPIRE125 | UC | 975 | *Clinical remission rate at week 12 - RZB 1,200 mg 20.3%, PBO 6.2% (p<0.00001) *Clinical response rate at week 4 - RZB 1,200 mg 52.2%, PBO 30.5% (p<0.00001) *Clinical response rate at week 12 - RZB 1,200 mg 64.3%, PBO 35.7% (p<0.00001) |
||
| COMMAND126 | UC | 548 | *Clinical remission rate at week 52 - RZB 180 mg 40.2%, RZB 360 mg 37.6%, PBO-controlled withdrawal (WD) 25.1% (p<0.01) * Compared to the WD group, more patients in the RZB 180 mg and RZB 360 mg groups achieved endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain |
||
| Mirikizumab | IL-23p19 subunit | NCT02891226127 | CD | 191 | *Endoscopic response rate at week 12 - Mirikizumab 200 mg 25.8% (95% CI, 10.4-41.2, p=0.079), mirikizumab 600 mg 37.5% (95% CI, 20.7-54.3, p=0.003), mirikizumab 1,000 mg 43.8% (95% CI, 31.6-55.9, p<0.001), PBO 10.9% (95% CI, 3.3-18.6) *Endoscopic response rate at week 52 - Combined IV group 58.5%, SC group 58.7% |
| LUCENT-1129 | UC | 1,281 | *Clinical remission rate at week 12 (induction trial) - Mirikizumab 300 mg 24.2%, PBO 13.3% (p<0.001) |
||
| LUCENT-2129 | UC | 544 | *Clinical remission rate at week 40 (maintenance trial) - Mirikizumab 200 mg 49.9%, PBO 25.1% (p<0.001) |
||
| LUCENT-3130 | UC | - | [Among responders at week 52] *Clinical remission rate at week 104 (open-label extension study) - NRI 76.6%, mNRI 89.0%, and OC 98.3% *Clinical response rate at week 104 (open-label extension study) - NRI 74.5%, mNRI 87.2%, and OC 96.7% [Among those in remission at week 52] *Clinical remission rate at week 104 (open-label extension study) - NRI 65.6%, mNRI 76.1%, and OC 84.2% *Clinical response rate at week 104 (open-label extension study) - NRI 54.0%, mNRI 62.8%, and OC 70.1% |
||
| Guselkumab | IL-23p19 subunit | GALAXI-1132,133 | CD | 309 | *Clinical remission rate at week 12 - GUS 200 mg 57.4%, 600 mg 55.6%, 1,200 mg 45.9%, PBO 16.4% (all, p<0.05) *CDAI reduction at week 12 - GUS 200 mg: -160.4, GUS 600 mg: -138.9, GUS 1,200 mg: -144.9, PBO: -36.2 (all, p<0.05) *Clinical remission rate at week 48 - GUS 200 → 100 mg group 64%, GUS 600 → 200 mg group 73%, GUS 1,200 → 200 mg group 57% *Endoscopic remission rate at wee 48 - GUS 200 → 100 mg group 18%, GUS 600 → 200 mg group 17%, GUS 1,200 → 200 mg group 33% *Endoscopic response rate at week 48 - GUS 200 → 100 mg group 44%, GUS 600 → 200 mg group 46%, GUS 1,200 → 200 mg group 44% |
| GALAXI-2134 | CD | 508 | *Patients receiving GUS 200 mg IV had significantly higher clinical remission rates compared to PBO (GALAXI-2: 47.1% vs. 22.4%; GALAXI-3: 47.1% vs. 15.3%) and higher endoscopic response rates (GALAXI-2: 37.7% vs. 10.5%; GALAXI-3: 36.2% vs. 13.9%) at week 12 *In both trials, patients receiving GUS 100 mg SC q8w or 200 mg SC q4w achieved significantly more primary endpoints ("clinical response at week 12 + clinical remission at week 48" and "clinical response at week 12 + endoscopic response at week 48") compared to PBO (p<0.001) *Both doses of GUS (100 mg and 200 mg) were superior to UST in terms of endoscopic response, endoscopic remission, deep remission, and clinical remission + endoscopic response. |
||
| GALAXI-3134 | CD | 513 | |||
| QUASAR (phase 2b)135 | UC | 313 | *Clinical response rate at week 12 - GUS 200 mg 61.4%, GUS 400 mg 60.7%, PBO 27.6% (both p<0.001) *Clinical remission rate at week 12 - GUS 200 mg 25.7%, GUS 400 mg 25.2%, PBO 9.5% (both p=0.002) *Symptomatic remission rate at week 12 - GUS 200 mg 49.5%, GUS 400 mg 47.7%, PBO 20.0% (both p<0.001) *Endoscopic improvement rate at week 12 - GUS 200 mg 30.7% (p=0.001), GUS 400 mg 30.8% (p<0.001), PBO 12.4% *HEMI rate at week 12 - GUS 200 mg 20.8% (p=0.014), GUS 400 mg 27.1% (p<0.001), PBO 8.6% *Endoscopic normalization rate at week 12 - GUS 200 mg 17.8% (p=0.013), GUS 400 mg 14.0% (p=0.076), PBO 6.7% |
||
| QUASAR (phase 3)136 | UC | 701 | *Clinical remission rate at week 12 - GUS 22.6%, PBO 7.9% (p<0.001) *Symptomatic remission rate week 12 - GUS 49.9%, PBO 20.7% (p<0.001) *Endoscopic improvement rate at week 12 - GUS 26.8%, PBO 11.1% (p<0.001) *Histologic-endoscopic improvement - GUS 23.5%, PBO 7.5% (p<0.001) |
||
| Brazikumab | IL-23p19 subunit | NCT01714726139 | CD | 119 | *Clinical response rate at week 8 - Brazikumab 49.2%, PBO 26.7% (p=0.010) *Clinical response rate at week 24 - Brazikumab (double-blind period) → brazikumab group 53.8%, PBO (double-blind period) → brazikumab group 57.7% |
IL, interleukin; CD, Crohn’s disease; UST, ustekinumab; IV, intravenous; PBO, placebo; q12w, every 12 weeks; q8w, every 8 weeks; UC, Ulcerative colitis; SC, subcutaneous; RZB, risankizumab; HEMI, histological-endoscopic mucosal improvement; CI, confidence interval; NRI, nonresponder imputation; mNRI modified nonresponder imputation; OC, observed case; GUS, guselkumab; CDAI, Crohn’s Disease Activity Index; q4w, every 4 weeks.