Table 3.
Advanced therapy PBO-controlled RCTs in UC. Efficacy and safety for new studies from February 2013 to August 2020.
| Medication Class vs PBO | Author, Year | N | (1) Primary and (2) Key Secondary Endpoints |
Endpoints Met | Study Limitations and Population |
|---|---|---|---|---|---|
|
| |||||
| ADA | Suzuki 201427 | 273 | (1) Clinical response, mucosal healing, and remission at wks 8 and 52 | Induction with ADA 160/80 mg led to early response and mucosal healing. Maintenance ADA had greater rates of long-term response (31%), remission (23%), and mucosal healing (29%) vs PBO. |
Efficacy and safety of ADA in Japanese patients with moderately to severely active UC. ADA 80/40 (80 mg at wk 0 then 40 mg every other wk) vs ADA 160/80 (160/80 mg at wk 0/2 then 40 mg every other wk) vs PBO. |
| Reinisch 201328 | 576 | (1) Clinical remission, clinical response, and mucosal healing at wk 52 for ITT-A3 and ITT-E groups | Rates of remission, response, and healing similar for both groups. ADA effective for maintaining clinical remission. | 52-week efficacy of ADA in patients with moderately to severely active UC who failed CS and/or immunosuppressants. Results of 52 wk open-label follow-up of patients with moderate to severe UC who participated in ULTRA 1. ITT-A3 is ITT amended protocol. Originally 2 arms, now 3 arms: ADA 160/80 mg (160 mg at wk 0, 80 mg at wk 2) and 40 mg at wks 4 and 6, vs ADA 80/40 (80 mg at wk 0, 40 mg at wk 2, 4, and 6), vs PBO. ITT-E is any version of protocol. Patients who received ≥ 1 injection of study drug enrolled at any time. |
|
| Sandborn 201329 | ULTRA 2: 248 | (1) Clinical response, remission, and mucosal healing at wk 52 (2) Steroid-free remission and steroid discontinuation rates |
49.6% achieved clinical response, 30.9% clinical remission, and 43.1% mucosal healing at wk 52. 21.1% achieved steroid-free remission and 37.8% were steroid-free. |
1-yr maintenance outcomes among patients with moderately to severely active UC who responded to induction therapy with ADA: subgroup analyses from ULTRA 2. | |
| Colombel 201430 | ULTRA 1: 600 ULTRA 2: 1094 |
(1) Remission, mucosal healing, and improved QOL assessed in ULTRA 1 and 2 up to wk 208 (2) Maintenance of remission and mucosal healing in ULTRA 3 |
ADA more effective than PBO in maintaining remission rates, mucosal healing, and improved QOL up to 4 yrs. | 4-yr maintenance treatment with ADA in patients with moderately to severely active UC: data from ULTRA 1, 2, and 3. | |
| GOL | Gibson 201631 | 1240 | (1) Assess safety and maintenance of efficacy from end of main study through the first year | Patients on SC GOL every 4 wks through 2 yrs maintained clinical benefits and reduced CS use. No new safety signals observed. |
Maintenance of efficacy and continuing safety of GOL for active UC: PURSUIT-SC maintenance study extension through 1 yr. |
| Hibi 201732 | 144 | (1) Clinical response through maintenance at wk 54 (2) Clinical remission and mucosal healing at maintenance wk 30 and 54 |
Patients on SC GOL maintained clinical response at wk 54 (56.3%) vs PBO (19.4%). At wk 30 and 54, 50% achieved clinical remission vs PBO (6.5%), and 59.4% experienced mucosal healing vs PBO (16.1%). |
Efficacy and safety of GOL 52-week maintenance therapy in Japanese patients with moderate to severely active UC: a phase III, double-blind, randomized, PBO-controlled study (PURSUIT-J study). Induction phase was 200 mg at wk 0 and 100 mg at wk 2 through 6 wks. Then entered maintenance phase at 100 mg vs PBO every 4 wks for 52 wks. | |
| Sandborn 201433 | 1064 | (1) Phase III endpoint clinical response at wk 6 (2) Clinical remission, mucosal healing, and change in IBDQ scores |
Rates of clinical response at wk 6 were 51.0% and 54.9% for patients given 200 mg/100 mg and 400 mg/ 200 mg GOL vs 30.3% PBO. Rates of remission, healing, and change in IBDQ greater for both GOL groups vs PBO (P < 0.05). |
SC GOL induces clinical response and remission in patients with moderate to severe UC. PURSUIT-SC study Phase II: dose-finding to evaluate dose-response relationship and select IV GOL induction regimens for further evaluation. Phase III: dose-confirming to evaluate safety and efficacy of selected regimens. Phase II: 1:1:1:1 at GOL doses 100/50 mg, 200/100 mg or 400/200 mg. After phase II dose-finding data analyses, 200/100 mg and 400/200 mg doses selected for further evaluation. In phase III: 1:1:1. |
|
| Sandborn 201434 | 464 | (1) Clinical response/remission at wk 54 (2) Clinical remission and mucosal healing at wk 30 and 54 |
Clinical remission and had mucosal healing (27.8% and 42.4%) than patients given PBO (15.6% and 26.6%; P = 0.004 and P = 0.002, respectively) or 50 mg GOL (23.2% and 41.7%, respectively). | Not powered to detect a statistical difference between the GOL and PBO groups for clinical remission. | |
| Rutgeerts 201535 | 291 | (1) Dose-response relationship (2) Clinical remission and mucosal healing |
No dose-response was observed in Phase II. Efficacy with single-dose GOL IV induction was lower than expected. No difference between receiving GOL vs PBO. |
RCT: a PBO-controlled study of IV GOL induction therapy for UC. PURSUIT-IV study: Phase II: 1:1:1:1 at 1, 2, or 4 mg/kg Phase III: 1:1:1 at 2 or 4 mg/kg |
|
| MTX | Carbonnel 201536 | 111 | (1) Steroid-free remission at wk 16 (2) Clinical remission and endoscopic healing without steroids at wk 16 and/or wk 24 |
MTX not superior to PBO. No difference. |
MTX is not superior to PBO in inducing steroid-free remission but induces steroid-free clinical remission in a larger proportion of patients with UC. |
| Herfarth 201837 | 179 | (1) Patients who remained relapse free and in remission at wk 48 without use of steroids/other medication | MTX not superior to PBO in preventing relapses, maintaining of steroid-free response, or remission in UC. | ||
| APR | Danese 202038 | 170 | (1) Clinical remission at wk 12 (defined by total Mayo score < 2) | Not met. 30 mg = 31.6% 40 mg = 21.8% PBO = 12.1% |
APR: 30 mg (n = 57) APR: 40 mg (n = 55) PBO: (n = 58) |
| TOF | Panes 201539 | 194 | (1) Effect of TOF on PROs (IBDQ) and (IBD PRITI) at wk 8 | IBDQ score: improvement significantly greater for TOF 15 mg BID vs PBO. On IBD PRITI, most patients reported satisfaction for 15 mg BID. |
0.5 mg or 3 mg or 10 mg or 15 mg or PBO BID. |
| Sandborn 201740 | 1 and 2: 598 and 541 Sustain: 593 |
(1) OCTAVE Induction 1 and 2: Remission at wk 8 (2) OCTAVE Sustain: Remission at wk 52 |
OCTAVE 1: remission in 18.5% patients vs 8.2% PBO OCTAVE 2: remission in 16.6% patients vs 3.6% PBO Remission 34.3% for 5 mg patients and 40.6% for 10 mg vs 11.1% PBO |
TOF as induction and maintenance therapy for UC. 3 phase III trials: OCTAVE Induction 1 and 2, OCTAVE Sustain. OCTAVE Induction 1 and 2: 10 mg BID vs PBO for 8 wks. OCTAVE Sustain: 5 or 10 mg vs PBO for 52 wks. |
|
| UST | Sands 201941 | Induction: 961 Maintenance: 523 |
(1) Clinical remission at wk 8 (Induction) (2) Clinical remission at wk 44 (Maintenance) |
Remission at wk 8 higher for patients who received 130 mg (15.6%) or 6 mg/kg (15.5%) than PBO (5.3%). Remission at wk 44 higher for patients given 90 mg every 12 wks (38.4%) or every 8 wks (43.8%) than PBO (24%). |
UST as induction and maintenance therapy for UC. 8-wk induction trial: 130 mg IV vs weight-range-based dose (6 mg/kg) vs PBO. 44-wk maintenance trial: 90 mg every 12 wks or 8 wks vs PBO. |
ADA: adalimumab; APR: apremilast; BID: 2 times daily; CS: corticosteroid; CUCQ: Crohn’s and Ulcerative Colitis Questionnaire; GOL: golimumab; IBD PRITI: Inflammatory Bowel Disease Patient-Reported Treatment Impact survey; IBDQ: Inflammatory Bowel Disease Questionnaire; ITT: intent-to-treat analysis; IV: intravenous; MTX: methotrexate; OCTAVE: Oral Clinical Trials for Tofacitinib in Ulcerative Colitis; PBO: placebo; PRO: patient-reported outcome; QOL: quality of life; SC: subcutaneous; TOF: tofacitinib; UC: ulcerative colitis; ULTRA: Ulcerative Colitis Long-Term Remission and Maintenance with Adalimumab; UST: ustekinumab.