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STELARA® (ustekinumab)
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Effects of STELARA on Endoscopic and Histologic Outcomes in Ulcerative Colitis: UNIFI Clinical Trial Program
Last Updated: 01/10/2025
Click on the following links to related sections within the document: Phase 3 UNIFI Clinical Trials and UNIFI Long-Term Extension.
Abbreviations: AE, adverse event; CRP, C-reactive protein; HEMI, histologic-endoscopic mucosal improvement; IV, intravenous; LTE, long-term extension; q8w, every 8 weeks; q12w, every 12 weeks; R, randomization; SC, subcutaneous; TNF, tumor necrosis factor; UC, ulcerative colitis; UST, ustekinumab.
a
Click on the following links to related sections within the document: Phase 3 UNIFI Clinical Trials and UNIFI Long-Term Extension.
Abbreviations: AE, adverse event; CRP, C-reactive protein; HEMI, histologic-endoscopic mucosal improvement; IV, intravenous; LTE, long-term extension; q8w, every 8 weeks; q12w, every 12 weeks; R, randomization; SC, subcutaneous; TNF, tumor necrosis factor; UC, ulcerative colitis; UST, ustekinumab.
aSands (2019).1 bSands (2018).2 cSands (2019).3 dLi (2019).4 eLi (2019).5 gLi (2020).6 fLeong (2022).7 hDanese (2023).8 iPeyrin-Biroulet (2023).9 jConventional therapies included corticosteroids, immunomodulators; and biologic therapies included ≥1 TNF blocker and/or vedolizumab. k260 mg (weight ≤55 kg), 390 mg (weight >55 kg but ≤85 kg), or 520 mg (weight >85 kg). lIncluding those not achieving response to IV placebo who received an induction dose of UST ~6 mg/kg IV at week 8 and responded at week 16. mFrom week 56 onward in the LTE, based on clinical judgment of the investigator, dose adjustment at any time was allowed: patients in the placebo SC arm could receive UST 90 mg SC q8w, patients in the UST 90 mg SC q12w arm could receive UST 90 mg SC q8w, and patients in the UST 90 mg SC q8w arm could continue on UST 90 mg SC q8w (sham dose adjustment). nSee study details for data regarding the 130 mg induction dose and q12w maintenance dosing. oP<0.05. pValues are reported as mean±standard deviation. qNot significant. rP<0.001. sPatients with both stool frequency and rectal bleeding Mayo subscores missing at a visit were considered to not be in symptomatic remission for that visit. Patients who had (a) had an ostomy or colectomy; or (b) had discontinued a study agent due to lack of therapeutic effect or due to an AE of worsening of UC after week 44 and before the designated visit, were considered not to be in symptomatic remission. Patients with a missing value for corticosteroid use had the last available value carried forward. tPatients were included in their randomized group at maintenance week 0, regardless of whether they had a dose adjustment during the LTE. uOnly patients who had an observed endoscopy subscore at week 200 and those who had treatment failure (ie, had an ostomy or a colectomy, or discontinued study agent due to lack of therapeutic effect or due to an AE of worsening of UC) prior to week 200 were included. vBased on the local endoscopy subscore.
SUMMARY
- Summarized in this response are relevant clinical data from the pivotal UNIFI clinical trial program.
- The safety and efficacy of STELARA therapy for the treatment of adults with moderately to severely active ulcerative colitis (UC) was evaluated in the phase 3 clinical trial program (UNIFI).1-
3 During induction therapy at week 8, treatment with intravenous (IV) STELARA resulted in significantly higher rates of endoscopic improvement, histologic improvement, as well as histologic-endoscopic mucosal improvement (HEMI) compared to the placebo group.4 Additionally, histologic improvement at week 8 was associated with lower disease activity and greater clinical improvement. - Similarly, during maintenance therapy at week 44 of the UNIFI maintenance study, significantly greater proportions of patients treated with subcutaneous (SC) STELARA achieved endoscopic improvement, histologic improvement, and HEMI compared to the placebo group. Among patients randomized to STELARA treatment, histologic improvement or HEMI after induction was associated with positive clinical outcomes at week 44 compared to those with only endoscopic improvement after induction.5
- Patients who achieved HEMI at week 8 of induction or week 44 of maintenance had lower disease activity and inflammatory burden from week 44 of the UNIFI maintenance study to week 92 of the long-term extension (LTE), as measured by mean partial Mayo score, mean stool frequency, mean C-reactive protein (CRP), and mean fecal calprotectin (FCP) levels.6 Additionally, patients who achieved disease clearance 8 weeks after IV induction were reported to have higher long-term symptomatic remission and a longer time to treatment failure compared to those with symptomatic remission without HEMI or neither symptomatic remission nor HEMI through 4 years
.9 - Higher symptomatic remission and corticosteroid-free symptomatic remission rates at weeks 92 and 152 were observed in patients who achieved HEMI after induction compared with patients who achieved endoscopic or histologic improvement alone. The differences were statistically significantly greater at week 152 and only numerically greater at week 92. Among the 205 patients who were randomized to STELARA at maintenance baseline and continued treatment in the LTE, approximately two-thirds of patients achieved endoscopic improvement at 4 years.7,
8 - A post hoc analysis compared efficacy outcomes between patients with moderate-to-severe UC who achieved an early response and those who achieved a delayed response to STELARA at 1 year.10
CLINICAL DATA
- A phase 3, randomized, double-blind, placebo-controlled, multicenter clinical program (UNIFI) evaluated the efficacy and safety of STELARA therapy in adult patients with moderately to severely active UC. The program consisted of 2 studies: IV induction study and SC maintenance study.1-3
- Patients enrolled had demonstrated an inadequate response to or were unable to tolerate conventional (ie, corticosteroids, immunomodulators) or biologic therapies (ie, 1 or more tumor necrosis factor blockers and/or vedolizumab).1,2
- During the induction study (8 weeks in duration), patients were randomized 1:1:1 at week 0 (baseline) to receive a single IV induction dose of STELARA 130 mg or a dose approximating STELARA 6 mg/kg (~6 mg/kg): 260 mg (weight ≤55 kg), 390 mg (weight >55 kg but ≤85 kg), or 520 mg (weight >85 kg) or placebo.1,2
- Patients who demonstrated a clinical response to STELARA IV induction treatment at week 8 (and those who did not have a response to IV placebo who then received an induction dose of STELARA ~6 mg/kg IV at week 8 and had a response at week 16) were eligible to enter the 44-week maintenance study and were randomized 1:1:1 to receive STELARA 90 mg SC every 8 weeks (q8w), STELARA 90 mg SC q12w, or SC placebo.1,3
- During the induction study, endoscopic improvement (major secondary endpoint), histologic improvement, and HEMI (other efficacy endpoints) were evaluated at week 8. Similarly, during the maintenance study, endoscopic improvement (major secondary endpoint), histologic improvement, and HEMI (other efficacy endpoints) were assessed at week 44.1
- During the UNIFI induction and maintenance studies, colonic biopsies were collected.1,5
- Endoscopic improvement was defined as a Mayo endoscopy score ≤1.4,5
- Histologic improvement (derived from features in Geboes score that are correlated with endoscopic mucosal response) was defined as an absence of erosion or ulceration or granulation tissue, absence of crypt destruction, and <5% of crypts with epithelial neutrophil infiltration.4,5
- HEMI was defined as achieving both endoscopic improvement and histologic improvement.4,5
Patient Characteristics
Efficacy
Induction Study - Week 8 Results
- Endoscopic improvement was achieved in 26.3% (84/320), 27.0% (87/322), and 13.8% (44/319) of patients receiving STELARA 130 mg IV, STELARA ~6 mg/kg IV, and placebo, respectively (P<0.001 for both comparisons versus [vs] placebo).4
- Histologic improvement was achieved in 37.9% (113/298), 35.6% (105/295), and 21.9% (65/297) of patients receiving STELARA 130 mg IV, STELARA ~6 mg/kg IV, and placebo, respectively (P<0.001 for both comparisons vs placebo).4
- HEMI was achieved in 20.3% (64/316), 18.4% (58/315), and 8.9% (28/316) of patients receiving STELARA 130 mg IV, STELARA ~6 mg/kg IV, and placebo, respectively (P<0.001 for both comparisons vs placebo).4
- Histologic improvement was significantly associated with endoscopic improvement at week 8 (P<0.0001).4
- Additionally, at week 8, histologic improvement was also associated with other clinical improvements. See Table: Clinical Outcomes for Patients with or without Histologic Improvement at Week 8 in the UNIFI Induction Study.
| Clinical Outcomes | Histologic Improvementa | Without Histologic Improvementa | P-Valueb | |
|---|---|---|---|---|
| Week 8 | n=283 | n=533 | ||
| Mayo score | 3.95±2.57 | 6.89±2.53 | <0.0001 | |
| Partial Mayo Score | 2.45±1.84 | 4.39±2.21 | <0.0001 | |
| Stool frequency | 1.09±0.95 | 1.81±1.03 | <0.0001 | |
| Rectal bleeding | 0.30±0.56 | 0.86±0.89 | <0.0001 | |
| Change in Mayo score | -4.53±2.65 | -2.15±2.39 | <0.0001 | |
| Change in partial Mayo score | -3.46±2.14 | -1.89±2.12 | <0.0001 | |
| Change in stool frequency | -1.08±1.01 | -0.63±0.90 | <0.0001 | |
| Change in rectal bleeding | -1.18±0.91 | -0.69±0.96 | <0.0001 | |
| aValues are reported as mean±standard deviation. bP-values based on t-test. | ||||
Maintenance Study - Week 44 Results (or 52 Weeks After Induction Dose)
- At week 44 of the UNIFI maintenance study, in patients who responded to STELARA induction and were randomized to maintenance treatment, significantly greater proportions of patients treated with STELARA 90 mg SC q12w or STELARA 90 mg SC q8w achieved endoscopic improvement, histologic improvement, and HEMI compared to the placebo group.5
- Endoscopic improvement: 43.6% (75/172) for STELARA 90 mg SC q12w and 51.1% (90/176) for STELARA 90 mg SC q8w vs 28.6% (50/175) for placebo (P=0.002 and P<0.001, respectively).
- Histologic improvement: 54.0% (88/163) for STELARA 90 mg SC q12w and 59.3% (99/167) for STELARA 90 mg SC q8w vs 32.9% (55/167) for placebo (P<0.001 for both comparisons).
- HEMI: 38.8% (66/170) for STELARA 90 mg SC q12w and 45.9% (79/172) for STELARA 90 mg SC q8w vs 24.1% (41/170) for placebo (P=0.002 and P<0.001, respectively).
- For all patients, irrespective of the maintenance treatment, histologic improvement at week 44 was associated with lower disease activity and greater improvement of disease. See Table: Clinical Outcomes for Patients with or without Histologic Improvement At Week 44 of the UNIFI Maintenance Study.
| Clinical Outcomes | Histologic Improvement at Week 44b | Without Histologic Improvement at Week 44b | P-Valuec |
|---|---|---|---|
| Week 44 | n=344 | n=235 | |
| Mayo score | 1.88±1.75 | 5.94±2.64 | <0.0001 |
| Partial Mayo score | 1.01±1.11 | 3.56±2.30 | <0.0001 |
| Stool Frequency Score | 0.60±0.72 | 1.49±1.02 | <0.0001 |
| Rectal bleeding score | 0.04±0.21 | 0.70±0.85 | <0.0001 |
| Change in Mayo score from baseline | -1.57±2.05 | 1.59±2.88 | <0.0001 |
| Change in partial Mayo score from baseline | -0.75±1.30 | 1.29±2.39 | <0.0001 |
| Change in stool frequency score from baseline | -0.22±1.00 | 0.40±0.70 | <0.0001 |
| Change in rectal bleeding score from baseline | -0.10±0.38 | 0.50±0.88 | <0.0001 |
| aIrrespective of treatment, including placebo and both STELARA maintenance groups. bValues are reported as mean±standard deviation. cP-values based on t-test. | |||
- For patients randomized to STELARA 90 mg SC q12w or q8w, histologic improvement after induction was associated with positive clinical outcomes at week 44 and sustained positive clinical outcomes at weeks 8 and 44 of the UNIFI maintenance study. See Table: Proportions of Patients with or without Histologic Improvement After Induction Who Achieved Clinical Outcomes at Week 44 and at Weeks 8 and 44 of the UNIFI Maintenance Study.
| Clinical Outcomes, n (%) | Histologic Improvement After Induction | Without Histologic Improvement After Induction | P-Valueb |
|---|---|---|---|
| At week 44 | n=140 | n=124 | |
| Endoscopic improvementc | 87 (62.0) | 58 (47.0) | 0.0135 |
| HEMId | 82 (59.0) | 53 (43.0) | 0.0135 |
| Clinical remissione | 76 (54.0) | 49 (40.0) | 0.0191 |
| Steroid-free clinical remissionf | 73 (52.0) | 48 (39.0) | 0.0354 |
| At week 8 and week 44 | |||
| Endoscopic improvementc | 44 (31.0) | 7 (6.0) | <0.0001 |
| HEMId | 56 (40.0) | 0 | <0.0001 |
| Clinical remissione | 36 (26.0) | 5 (4.0) | <0.0001 |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement. aPatients randomized to STELARA 90 mg subcutaneously every 12 weeks or every 8 weeks in the maintenance study. bP-values based on t-test. cMayo endoscopy score of 0 or 1. dAchieving both histologic improvement and endoscopic improvement. eMayo score ≤2 with no individual subscore >1. fIn clinical remission and not receiving corticosteroids. | |||
- Additionally, among patients randomized to STELARA, those who had HEMI after induction were more likely to achieve positive clinical outcomes at week 44 compared to those with only endoscopic improvement after induction. See Table: Proportions of Patients with or without HEMI After Induction Who Achieved Clinical Outcomes at Week 44 of the UNIFI Maintenance Study.
| Clinical Outcomes, n (%) | Endoscopic Improvement After Induction (N=115) | P-Valueb | |
|---|---|---|---|
| Histologic Improvement After Induction | Without Histologic Improvement After Induction | ||
| At week 44 | n=92 | n=23 | |
| Clinical responsec | 77 (84.0) | 12 (52.0) | 0.0038 |
| Clinical remissiond | 56 (61.0) | 9 (39.0) | 0.0983 |
| Steroid-free clinical remissione | 53 (58.0) | 8 (35.0) | 0.0628 |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement. aResponse irrespective of induction treatment. Clinical outcomes in randomized patients who received STELARA 90 mg subcutaneously every 12 weeks or every 8 weeks. bP-values based on Fisher’s exact test for categorical variables. cMayo reduction from screening by ≥30% and ≥3 points, with either a ≥1 point drop in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. dMayo score ≤2 with no individual subscore >1. eIn clinical remission and not receiving corticosteroids. | |||
2 Years
Study Design/Methods
- The LTE study started after the 44-week UNIFI maintenance study.
- Patients in the LTE continued to receive STELARA 90 mg SC q8w (n=143), STELARA 90 mg SC q12w (n=141), or placebo SC (n=115).
- Patients who were assigned to placebo SC during the maintenance study were discontinued after study unblinding, which occurred after the analysis of maintenance study data.
- From week 56 onward in the LTE, based on clinical judgment of the investigator, dose adjustment at any time was allowed:
- Patients in the placebo SC arm could receive STELARA 90 mg SC q8w.
- Patients in the STELARA 90 mg SC q12w arm could receive STELARA 90 mg SC q8w.
- Patients in the STELARA 90 mg SC q8w arm could continue on STELARA 90 mg SC q8w (sham dose adjustment).
- Analyses were conducted in patients who were randomized to receive STELARA maintenance therapy and continued STELARA in the LTE.
- Two colonic biopsies were collected from the distal colon during endoscopic evaluation at screening, 8 weeks following a single IV induction administration of STELARA, and at week 44 of maintenance to evaluate HEMI.
- Histologic improvement, endoscopic improvement, and HEMI were defined as previously noted in the UNIFI induction and maintenance overall study design.
Results
- Patients who achieved HEMI at week 8 of induction or week 44 of maintenance had lower disease activity from weeks 44 through 92 of the LTE (measured by mean partial Mayo score and mean stool frequency). See Table: Partial Mayo Score and Stool Frequency from Week 44 through Week 92 Among Randomized Patients Treated with STELARA in the LTE.
| Maintenance | |||||
|---|---|---|---|---|---|
| Week 44 | Week 56 | Week 68 | Week 80 | Week 92 | |
| Mean partial Mayo score | |||||
| By HEMI status after induction therapy | |||||
| With HEMI at induction week 8 (n=80) | 1.23 | 1.03 | 0.98 | 0.86 | 0.74 |
| Without HEMI at induction week 8 (n=172) | 1.91 | 1.48 | 1.42 | 1.45 | 1.40 |
| By HEMI status after maintenance therapy | |||||
| With HEMI at maintenance week 44 (n=142) | 0.75 | 0.90 | 0.92 | 1.01 | 0.94 |
| Without HEMI at maintenance week 44 (n=118) | 2.68 | 1.70 | 1.66 | 1.55 | 1.42 |
| Mean stool frequency | |||||
| By HEMI status after induction therapy | |||||
| With HEMI at induction week 8 (n=80) | 0.64 | 0.51 | 0.56 | 0.48 | 0.39 |
| Without HEMI at induction week 8 (n=172) | 0.98 | 0.85 | 0.83 | 0.81 | 0.76 |
| By HEMI status after maintenance therapy | |||||
| With HEMI at maintenance week 44 (n=142) | 0.47 | 0.53 | 0.55 | 0.56 | 0.51 |
| Without HEMI at maintenance week 44 (n=118) | 1.23 | 0.90 | 0.95 | 0.84 | 0.74 |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement; LTE, long-term extension. | |||||
- Patients who achieved HEMI at week 8 of induction or week 44 of maintenance had lower inflammatory burden from weeks 44 through 92 of the LTE, as measured by mean CRP and mean fecal calprotectin levels. See Table: CRP and Fecal Calprotectin Levels from Week 44 through Week 92.
| Without HEMI After Inductiona,b | With HEMI After Inductiona,b | P-Valuec | Without HEMI at Maintenance Week 44a | With HEMI at Maintenance Week 44a | P-Valuec | |
|---|---|---|---|---|---|---|
| N | 172 | 80 | 118 | 142 | ||
| CRP (mg/L, log2 transformed) | ||||||
| Week 44 | 0.78±1.99 | 0.43±1.85 | NS | 1.27±1.88 | 0.23±1.83 | <0.001 |
| Week 56 | 0.57±2.03 | 0.42±1.92 | NS | 0.97±2.06 | 0.27±1.86 | <0.01 |
| Week 68 | 0.72±2.18 | 0.38±1.72 | NS | 1.05±2.01 | 0.22±1.96 | <0.001 |
| Week 80 | 0.87±2.30 | 0.31±2.03 | NS | 1.09±2.22 | 0.28±2.09 | <0.01 |
| Week 92 | 0.76±2.26 | 0.29±2.00 | NS | 0.87±2.16 | 0.37±2.17 | NS |
| Fecal Calprotectin (mg/kg, log2 transformed) | ||||||
| Week 44 | 7.72±2.49 | 6.91±2.25 | <0.05 | 8.94±2.23 | 6.19±1.84 | <0.001 |
| Week 56 | 7.68±2.53 | 7.02±2.31 | <0.05 | 8.65±2.40 | 6.47±2.17 | <0.001 |
| Week 68 | 7.58±2.65 | 7.18±2.42 | NS | 8.33±2.57 | 6.71±2.38 | <0.001 |
| Week 80 | 7.76±2.56 | 7.39±2.59 | NS | 8.49±2.36 | 6.84±2.47 | <0.001 |
| Week 92 | 7.63±2.68 | 7.43±2.53 | NS | 8.40±2.54 | 6.83±2.52 | <0.001 |
| Abbreviations: CRP, C-reactive protein; HEMI, histologic-endoscopic mucosal improvement; NS, not significant (P>0.05). aValues are reported as mean±standard deviation. bInduction HEMI irrespective of treatment. cP-values based on t-test between patients with HEMI and those without HEMI; NS (P>0.05). | ||||||
- Patients who achieved HEMI after induction remained in the LTE study longer than those who did not achieve HEMI (mean retention of 364 days vs 354 days, respectively; P<0.05).
3 Years
Leong et al (2022)7 reported the effect of HEMI after STELARA induction therapy on long-term symptomatic outcomes through 3 years.
Study Design/Methods
- Patients in clinical response after 8 weeks of treatment with STELARA 130 mg or ~6 mg/kg (week 8 responders) were randomized to receive maintenance therapy with STELARA 90 mg q12w or q8w (randomized patients).
- Patients who were not in clinical response to initial dose of STELARA at week 8 but achieved response at week 16 after receiving a single dose of STELARA 90 mg SC at week 8 (week 16 responders) received maintenance therapy with STELARA 90 mg q8w (non-randomized patients).
- After 44 weeks of maintenance treatment, patients were given an option to continue treatment during the LTE.
Results
- Among 438 patients who responded to the STELARA induction therapy (at week 8 or week 16) and received the maintenance therapy, 116 (26.5%) achieved HEMI after induction, 30 (6.8%) achieved endoscopic improvement without histologic improvement, and 106 (24.2%) achieved histologic improvement without endoscopic improvement.
- Higher symptomatic remission and corticosteroid-free symptomatic remission rates at weeks 92 and 152 were observed in patients who achieved HEMI compared with patients who achieved endoscopic or histologic improvement alone. The differences were statistically significantly greater at week 152 and only numerically greater at week 92.
- For symptomatic and corticosteroid-free symptomatic remission by histologic and endoscopic improvement, see Table: Long-term Symptomatic Outcomes by Histologic and Endoscopic Improvement Status 8 Weeks After Induction Therapy in Patients Treated with the STELARA Maintenance Therapy.
| Clinical Outcome, n (%) | HEMI (n=116) | Endoscopic Improvement without Histologic Improvement (n=30) | Histologic Improvement without Endoscopic Improvement (n=106) |
|---|---|---|---|
| Week 92 | |||
| Symptomatic remission | 83 (71.6) | 19 (63.3); P=0.381b | 70 (66.0); P=0.388b |
| Corticosteroid-free symptomatic remission | 79 (68.1) | 17 (56.7); P=0.282b | 69 (65.1); P=0.670b |
| Week 152 | |||
| Symptomatic remission | 81 (69.8) | 14 (46.7); P=0.030b | 58 (54.7); P=0.026b |
| Corticosteroid-free symptomatic remission | 77 (66.4) | 12 (40.0); P=0.011b | 55 (51.9); P=0.030b |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement. aPatients with both stool frequency and rectal bleeding Mayo subscores missing at any visit were considered to not be in symptomatic remission for that visit. Patients who had (a) had an ostomy or colectomy; or (b) had discontinued a study agent due to lack of therapeutic effect or due to an adverse event of worsening of ulcerative colitis after week 44 and before the designated visit, were considered not to be in symptomatic remission. Patients with a missing value for corticosteroid use had the last available value carried forward. bP-value based on Fisher’s exact test. | |||
4 Years
Danese et al (2023)8 reported the final clinical outcomes, including the endoscopy subscore, through 4 years of STELARA treatment.
Study Design/Methods
- Outcomes based on the Mayo score were assessed at the final efficacy visit at week 200.
- Patients who experienced treatment failure before week 200 (ie, had ostomy or colectomy or discontinued STELARA due to the lack of therapeutic effect or worsening of UC) were also included and were imputed as nonresponders.
Results
- For clinical and endoscopic outcomes among the 205 patients who were randomized to receive STELARA at maintenance baseline and continued treatment in the LTE, who either had Mayo score data (including endoscopy) at week 200 or had experienced treatment failure, see Table: Clinical and Endoscopic Outcomes through 4 Years Among Randomized Patients Treated with STELARA in the LTE.
- Approximately two-thirds of patients achieved endoscopic improvement at 4 years.
| Outcome, n (%) | STELARA 90 mg SC q12w (n=105) | STELARA 90 mg SC q8w (n=100) | Combined STELARA (n=205) |
|---|---|---|---|
| Clinical remission | 61 (58.1) | 58 (58.0) | 119 (58.0) |
| Clinical response | 82 (78.1) | 82 (82.0) | 164 (80.0) |
| Modified Mayo score response | 81 (77.1) | 82 (82.0) | 163 (79.5) |
| Endoscopic improvementc | 71 (67.6) | 67 (67.0) | 138 (67.3) |
| Abbreviations: LTE, long-term extension; q8w, every 8 weeks; q12w, every 12 weeks; SC, subcutaneous. aPatients were included in their randomized group at maintenance week 0, regardless of whether they had a dose adjustment during the LTE. bOnly patients who had an observed endoscopy subscore at week 200 and those who had treatment failure (ie, had an ostomy or a colectomy, or discontinued study agent due to lack of therapeutic effect or due to an AE of worsening of UC) prior to week 200 were included. cBased on local endoscopy subscore. | |||
- Based on an alternative (as observed case) analysis without imputation for treatment failure, among 171 randomized patients who continued to receive STELARA through the LTE and had an endoscopy score at week 200, 69.6% achieved clinical remission, 95.9% achieved clinical response, 95.3% achieved modified Mayo score response, and 80.7% achieved endoscopic improvement.
Peyrin-Biroulet et al (2023)9 reported the long-term outcomes in patients who achieved symptomatic remission after induction, with or without HEMI, through 4 years of STELARA treatment.
Study Design/Methods
- Patients in clinical response after 8 weeks of IV induction with STELARA (130 mg or ~6 mg/kg) or placebo were randomized to receive maintenance therapy with SC STELARA 90 mg q12w or q8w or placebo.
- Patients who completed 44 weeks of maintenance treatment were given an option to continue treatment during the LTE.
- Efficacy endpoints 8 weeks after IV induction were categorized as disease clearance (defined as achieving both HEMI and symptomatic remission), symptomatic remission without HEMI, and neither symptomatic remission nor HEMI.
Results
- For symptomatic remission through 4 years in patients with disease clearance, symptomatic remission without HEMI, or neither symptomatic remission nor HEMI 8 weeks after IV STELARA induction, see Table: Long-Term Outcomes in Patients Who Achieved Symptomatic Remission After Induction through 4 Years.
| Outcome, n (%) | Disease Clearance (n=79) | Symptomatic Remissiona without HEMIb (n=142) | Neither Symptomatic Remissiona nor HEMIb (n=82) |
|---|---|---|---|
| Week 44 | |||
| Symptomatic remissiona | 63 (79.7) | 98 (69.0) | 35 (42.7) |
| Corticosteroid-free remission | 60 (75.9) | 97 (68.3) | 34 (41.5) |
| Week 92 | |||
| Symptomatic remissiona | 63 (79.7) | 100 (70.4) | 41 (50.0) |
| Corticosteroid-free remission | 60 (75.9) | 98 (69.0) | 39 (47.6) |
| Week 152 | |||
| Symptomatic remissiona | 60 (75.9) | 78 (54.9) | 32 (39.0) |
| Corticosteroid-free remission | 57 (72.2) | 76 (53.5) | 31 (37.8) |
| Week 200 | |||
| Symptomatic remissiona | 58 (73.4) | 76 (53.5) | 37 (45.1) |
| Corticosteroid-free remission | 56 (70.9) | 74 (52.1) | 35 (42.7) |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement; IV, intravenous; SC, subcutaneous. aSymptomatic remission was defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. bHEMI was defined as having both histologic improvement (<5% neutrophils in the epithelium, no crypt destruction, and no erosions, ulcerations, or granulations) and endoscopic improvement (Mayo endoscopic subscore of 0 or 1). | |||
- Time to treatment failure (UC-related surgery or hospitalization, adverse event [AE], or discontinuation of treatment due to an AE or lack of efficacy) was longer in patients with disease clearance vs those in symptomatic remission without HEMI (P=0.004), and those with neither symptomatic remission nor HEMI (P=0.043).
UNIFI Post Hoc Analysis
Wong et al (2023)10 reported a post hoc analysis of the UNIFI trial, comparing long-term efficacy outcomes between patients with moderate-to-severe UC who achieved an early response and those who achieved a delayed response to STELARA.
Study Design/Methods
- Patients who achieved a clinical response after 8 weeks of treatment with STELARA IV 130 mg or 6 mg/kg (early responders) were rerandomized to receive maintenance therapy.
- Patients who did not achieve a clinical response to the initial dose of STELARA IV at week 8 but achieved a response at week 16 after receiving a single dose of STELARA 90 mg SC at week 8 (delayed responders) received maintenance therapy with STELARA 90 mg SC q8w.
- Patients who did not respond at week 8 or 16 were considered nonresponders and discontinued from the trial.
- Endoscopy with biopsy was performed at the end of induction therapy (week 8) and at the end of maintenance therapy (week 52), with an additional week 16 endoscopy performed for delayed responders.
- Clinical remission, adapted Mayo score clinical remission, patient-reported outcome-2 item remission, endoscopic improvement, endoscopic remission, and HEMI were evaluated at 1 year.
Results
- Among 642 patients who were treated with STELARA, 321 (50%) were early responders, 115 (17.9%) were delayed responders, and 205 (32.1%) were nonresponders.
- For clinical outcomes among early vs delayed responders, see Table: Outcomes at 1 Year Among Early vs Delayed Responders and Table: Outcomes at 1 Year Among Early vs Delayed Responders Based on Partial Mayo Score Response.
| 1-Year Outcome, n (%) | Early Responders (n=321) | Delayed Responders (n=115) | P-Value |
|---|---|---|---|
| Clinical remissiona | 132 (41.1) | 40 (34.8) | 0.233 |
| Adapted Mayo score clinical remissionb | 144 (44.9) | 43 (37.4) | 0.165 |
| PRO-2 remissionc | 121 (37.7) | 37 (32.2) | 0.291 |
| Endoscopic improvementd | 152 (47.4) | 46 (40.0) | 0.174 |
| Endoscopic remissione | 84 (26.2) | 27 (23.5) | 0.57 |
| HEMIf | 142 (44.2) | 43 (37.4) | 0.203 |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement; PRO, patient-reported outcome. aTotal Mayo score of ≤2 and no subscore of >1. bStool frequency subscore of ≤1 but not greater than baseline, rectal bleeding subscore of 0, Mayo endoscopic subscore of ≤1. cStool frequency and rectal bleeding subscores of 0. dMayo endoscopic subscore of ≤1. eMayo endoscopic subscore of 0. fGeboes highest grade of <3.2 and Mayo endoscopic subscore of ≤1. | |||
| 1-Year Outcome, n (%) | Early Responders (n=178) | Delayed Responders (n=94) | P-Value |
|---|---|---|---|
| Clinical remissionb | 89 (50.0) | 50 (53.2) | 0.617 |
| Adapted Mayo score clinical remissionc | 94 (52.8) | 50 (53.2) | 0.952 |
| PRO-2 remissiond | 101 (56.7) | 51 (54.3) | 0.695 |
| Endoscopic improvemente | 95 (53.4) | 50 (53.2) | 0.978 |
| Endoscopic remissionf | 59 (33.2) | 34 (36.2) | 0.617 |
| HEMIg | 90 (50.6) | 48 (51.1) | 0.937 |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement; pMS, partial Mayo score; PRO, patient-reported outcome. aPartial Mayo score response was defined as pMS ≤1 at week 16 (but not in pMS remission at week 8). bTotal Mayo score of ≤2 and no subscore of >1. cStool frequency subscore of ≤1 but not greater than baseline, rectal bleeding subscore of 0, Mayo endoscopic subscore of ≤1. dStool frequency and rectal bleeding subscores of 0. eMayo endoscopic subscore of ≤1. fMayo endoscopic subscore of 0. gGeboes highest grade of <3.2 and Mayo endoscopic subscore of ≤1. | |||
- For clinical outcomes among delayed responders, see Table: Outcomes at 1 Year Among Delayed Responders Stratified by Weight-Based vs Fixed Induction Doses of STELARA.
| 1-Year Outcome, n (%) | Weight-Based IV Dose STELARA 6 mg/kg (n=70) | Fixed IV Dose STELARA 130 mg (n=45) | P-Value |
|---|---|---|---|
| Clinical remissiona | 26 (37.1) | 14 (31.1) | 0.507 |
| Adapted Mayo score clinical remissionb | 26 (37.1) | 17 (37.8) | 0.945 |
| PRO-2 remissionc | 21 (30.0) | 16 (35.6) | 0.534 |
| Endoscopic improvementd | 27 (38.6) | 19 (42.2) | 0.697 |
| Endoscopic remissione | 17 (24.3) | 10 (22.2) | 0.799 |
| HEMIf | 25 (35.7) | 18 (40.0) | 0.643 |
| Abbreviations: HEMI, histologic-endoscopic mucosal improvement; PRO, patient-reported outcome. aTotal Mayo score of ≤2 and no subscore of >1. bStool frequency subscore of ≤1 but not greater than baseline, rectal bleeding subscore of 0, Mayo endoscopic subscore of ≤1. cStool frequency and rectal bleeding subscores of 0. dMayo endoscopic subscore of ≤1. eMayo endoscopic subscore of 0. fGeboes highest grade of <3.2 and Mayo endoscopic subscore of ≤1. | |||
Literature Search
A literature search of MEDLINE®
Summarized in this response are relevant clinical data from the pivotal UNIFI clinical trial program and a post-hoc analysis.
References
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