STELARA®
(ustekinumab)
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STELARA® (ustekinumab)
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Treatment of Adult Patients with Active Psoriatic Arthritis
Last Updated: 01/06/2025
Summary
- The PSUMMIT I study, which assessed the efficacy and safety of STELARA in reducing the signs and symptoms of active psoriatic arthritis (PsA) in adult patients, found that a significantly greater proportion of patients who received STELARA 45 mg or 90 mg achieved the primary endpoint of ≥20% improvement in symptoms according to the American College of Rheumatology (ACR20) at week 24 compared to placebo (42.4% and 49.5% vs 22.8%, respectively; P<0.001 for both comparisons). At week 16, the proportion of patients with ≥1 adverse event (AE) was similar between groups (41.8% [171/409] for combined STELARA groups; 42.0% [86/205] for placebo).1
, 2 - Additionally, the PSUMMIT II study, conducted in adult patients with active PsA who had been previously treated with or without an anti-TNF agent, found that STELARA 45 mg or 90 mg administered at weeks 0, 4, and every 12 weeks significantly reduced signs and symptoms of active PsA as measured by ACR20 response through week 24 vs placebo (43.7% and 43.8% vs 20.2%, respectively; P<0.001 for both comparisons). Through week 16, the number of patients reporting ≥1 AE was 63.1%, 60.6%, 54.8% for the STELARA 45-mg, STELARA 90-mg, and placebo groups, respectively.3
The safety and efficacy of STELARA was assessed in 927 patients (PSUMMIT I, n=615; PSUMMIT II, n=312), in two randomized, double-blind, placebo-controlled studies. Adult patients 18 years of age and older with active PsA (≥5 swollen joints [SJC] and ≥5 tender joints [TJC]) for ≥6 months despite nonsteroidal antiinflammatory (NSAID) or disease modifying antirheumatic (DMARD) therapy were eligible.
PSUMMIT I and PSUMMIT II
- Patients were randomized to receive STELARA 45 mg, 90 mg, or placebo at weeks 0, 4, and every 12 weeks thereafter. In PSUMMIT I, the final efficacy evaluation took place at week 100 (safety assessment at week 108) and at week 52 in PSUMMIT II (safety assessment at week 60).
- Stable doses of methotrexate (MTX, ≤25 mg/week), NSAIDs, and/or oral corticosteroids (≤10 mg/day prednisone) were permitted. All concomitant medications were to remain at stable doses through week 52. Approximately 50% of patients continued on stable doses of MTX across both studies.
- Patients treated with prior anti-TNF agents were excluded from PSUMMIT I.
- In PSUMMIT II, patients were eligible if they had ≥8 weeks of exposure to etanercept, golimumab, adalimumab, or certolizumab pegol, or 14 weeks of exposure to infliximab and/or documented evidence of anti-TNF agent intolerance/toxicity.
- At week 16, patients with <5% improvement in SJC and TJC entered blinded early escape (placebo to STELARA 45 mg; STELARA 45 mg to 90 mg; STELARA 90 mg to 90 mg).
- The primary endpoint in each study was the proportion of patients achieving an ACR20 response at week 24.
- Secondary endpoints included the following: ACR50/70, Disease Activity Score 28 using C-reactive protein (DAS28-CRP) response of good or moderate (European League Against Rheumatism [EULAR] response), change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response (in patients with ≥3% body surface area [BSA] involvement), and percent change from baseline in enthesitis and dactylitis scores (in affected patients) at week 24.
McInnes et al (2013)1 and Kavanaugh et al (2013 and 2015)2,4
Patient Characteristics
- Patients ranged from 18 to 81 years of age (median, 48 years), with a median PsA disease duration of 3.6 and 4.2 years in the placebo and combined STELARA groups, respectively.
| PBO (n=206) | STELARA 45 mg (n=205) | STELARA 90 mg (n=204) | |
|---|---|---|---|
| Week 24 | |||
| ACR20 P-value | 47 (22.8%) | 87 (42.4%) <0.0001 | 101 (49.5%) <0.0001 |
| ACR50 P-value | 18 (8.7%) | 51 (24.9%) <0.0001 | 57 (27.9%) <0.0001 |
| ACR70 P-value | 5 (2.4%) | 25 (12.2%) 0.0001 | 29 (14.2%) <0.0001 |
| DAS28-CRP/EULARa P-value | 71 (34.5%) | 135 (65.9%) <0.0001 | 138 (67.6%) <0.0001 |
| Median HAQ-DI change from baseline; median (IQR) P-value | -0.0 (-0·38 to 0.13) | -0.25 (-0·63 to 0.00) <0.0001 | -0.25 (-0·75 to 0.00) <0.0001 |
| Patients with ≥0.3 reduction in HAQ P-value | 58 (28.2%) | 98 (47.8%) <0.0001 | 97 (47.5%) <0.0001 |
| PASI 75b P-value | 16/146 (11.0%) | 83/145 (57.2%) <0.0001 | 93/149 (62.4%) <0.0001 |
| Patients with enthesitisc P-value | 111/137 (81.0%) | 96/140 (68.6%) 0.0179 | 90/148 (60.8%) 0.0002 |
| Patients with dactylitisd P-value | 70/92 (76.1%) | 56/99 (56.6%) 0.0050 | 53/95 (55.8%) 0.0038 |
| Week 52e | PBO→STELARA 45 mg (n=189) | STELARA 45 mg (n=205) | STELARA 90 mg (n=204) |
| ACR20 | 65.2% | 55.7% | 60.3% |
| ACR50 | 38.0% | 31.4% | 37.0% |
| ACR70 | 16.3% | 18.0% | 21.2% |
| DAS28-CRP/EULAR response | 74.5% | 72.7% | 74.6% |
| Median HAQ-DI change from baseline | -0.38 | -0.25 | -0.38 |
| Patients with ≥0.3 reduction in HAQ-DI | 53.8% | 47.4% | 51.3% |
| PASI 75b | 88/130 (67.7%) | 94/134 (70.1%) | 96/141 (68.1%) |
| Mean % change (median) in enthesitis score (modified MASES Index); Mean ± SD (median) | -47.63 ± 73.66 (-87.50) | -46.08 ± 85.99 (-83.33) | -56.47 ± 54.78 (-74.17) |
| Mean % change (median) in dactylitis score; Mean ± SD (median) | -68.38 ± 55.99 (-100.00) | -55.57 ± 79.00 (-100.00) | -55.17 ± 112.82 (-100.00) |
| Week 100g | PBO→STELARA 45 mg (n=189) | STELARA 45 mg (n=205) | STELARA 90 mg (n=204) |
| ACR20 | 62.7% | 56.7% | 63.6% |
| ACR50 | 37.3% | 38.8% | 46.0% |
| ACR70 | 18.6% | 24.7% | 22.2% |
| Median HAQ-DI change from baseline; median (IQR) | -0.38 (-0.63, 0.00) | -0.25 (-0.75, 0.00) | -0.38 (-0.81, 0.00) |
| Patients with ≥0.3 reduction in HAQ-DI | 50.3% | 47.8% | 51.7% |
| PASI 75f | 63.9% | 72.5% | 71.3% |
| % improvement (median) from baseline in enthesitis score (modified MASES Index), median (IQR) | 87.1 (0.0, 100.0) | 100.0 (9.1, 100.00) | 100.0 (0.0, 100.0) |
| % improvement (median) from baseline in dactylitis score, median (IQR) | 100.0 (32.2, 100.0) | 100.0 (66.7, 100.0) | 100.0 (60.0, 100.0) |
| Abbreviations: ACR20, 50, and 70, ≥20%, ≥50%, and ≥70% improvement in American College of Rheumatology criteria from baseline; DAS28-CRP, 28-joint disease activity score based on C-reactive protein; EULAR, European League Against Rheumatism; HAQ-DI, health assessment questionnaire disability index; IQR, interquartile range; MASES, Maastricht Ankylosing Spondylitis Enthesitis Score; PASI 75, ≥75% improvement in Psoriasis Area and Severity Index; PBO, placebo. aA good or moderate DAS28-CRP response. bIn patients with ≥3% BSA affected by psoriasis at baseline. cIn patients with psoriatic-arthritis-modified MASES Index ≥1 at baseline. dIn patients with dactylitis in 1 digit or more at baseline. eAll patients receiving placebo crossed over to receive STELARA 45 mg beginning at week 24. fIn patients with ≥3% BSA affected by psoriasis at baseline; n=440 at week 100. gAfter week 52, adjustments to concomitant medication doses/initiation of other concomitant therapies were allowed. | |||
While ACR responses were greater with STELARA vs placebo regardless of MTX use, differences were numerically larger among patients not taking MTX. There were no statistical analyses done comparing the impact of concomitant MTX use on efficacy measures.
- Through week 16, the proportion of patients with ≥1 AE was similar between groups (41.8% [171/409] for combined STELARA groups; 42.0% [86/205] for placebo). The most common AEs in patients receiving STELARA included: nasopharyngitis in 19 (4.6%) patients, upper respiratory tract infection in 14 patients (3.4%), and headache in 14 (3.4%) patients.
- During this period at least 1 serious AE was reported in 1.7% (7/409) of combined STELARA-treated and 2.0% (4/205) of placebo-treated patients.
- Through week 108, the average duration of follow up was 91.9 weeks for the combined STELARA treatment group. The proportion of patients with ≥1 AE was 61.9% (117/189), 77.1% (158/205), and 72.5% (148/204) in the placebo→STELARA 45-mg, STELARA 45-mg, and 90-mg groups, respectively.
- Serious AEs occurred in 7.9% (15/189), 12.7% (26/205), and 8.3% (17/204) of patients in the placebo→STELARA 45-mg, STELARA 45-mg, and 90-mg groups, respectively.
- There were 11 serious infections reported (1 in the placebo→STELARA 45-mg group and 5 each in the STELARA 45-mg and 90-mg groups).
- There were 4 malignancies: 1 in the placebo→STELARA 45-mg group (renal cell carcinoma), 1 in the STELARA 45-mg group (B-cell lymphoma) and 2 in the STELARA 90-mg group (1 each, basal cell carcinoma and squamous cell carcinoma).
- Seven patients reported ≥1 major adverse cardiac event (MACE) (2 in the placebo→STELARA 45-mg group, 4 in the STELARA 45-mg group, and 1 in the STELARA 90-mg group.
Patient Characteristics
- Patients ranged from 38 to 57 years of age, with a median PsA disease duration of 5.5, 5.3, and 4.5 years in the placebo, STELARA 45-mg, and STELARA 90-mg groups, respectively.
- Of the 180 patients who had previously been treated with at least 1 anti-TNF agent, >70% had an inadequate response or were intolerant to treatment with an anti-TNF agent and more than 50% had received ≥2 anti-TNF agents.
| PBO | STELARA 45 mg | STELARA 90 mg | |
|---|---|---|---|
| ACR20 (primary endpoint) | |||
| Overall | 21/104 (20.2%) | 45/103 (43.7%) P<0.001 | 46/105 (43.8%) P<0.001 |
| Previous anti-TNF agent | 9/62 (14.5%) | 22/60 (36.7%) P=0.006 | 20/58 (34.5%) P=0.011 |
| Anti-TNF agent naïve | 12/42 (28.6%) | 23/43 (53.5%) P=0.021 | 26/47 (55.3%) P=0.011 |
| ACR50 | |||
| Overall | 7/104 (6.7%) | 18/103 (17.5%) P<0.05 | 24/105 (22.9%) P<0.01 |
| Previous anti-TNF agent | 4/62 (6.5%) | 9/60 (15.0%) P=0.138 | 9/58 (15.5%) P=0.111 |
| Anti-TNF agent naïve | 3/42 (7.1%) | 9/43 (20.9%) P=0.084 | 15/47 (31.9%) P=0.004 |
| ACR70 | |||
| Overall | 3/104 (2.9%) | 7/103 (6.8%) P=0.190 | 9/105 (8.6%) P=0.078 |
| Previous anti-TNF agent | 1/62 (1.6%) | 3/60 (5.0%) P=0.322 | 3/58 (5.2%) P=0.286 |
| Anti-TNF agent naïve | 2/42 (4.8%) | 4/43 (9.3%) P=0.473 | 6/47 (12.8%) P=0.215 |
| PASI 75a | |||
| Overall | 4/80 (5.0%) | 41/80 (51.3%) P<0.001 | 45/81 (55.6%) P<0.001 |
| Previous anti-TNF agent | 1/50 (2.0%) | 20/44 (45.5%) P<0.001 | 20/41 (48.8%) P<0.001 |
| Anti-TNF agent naïve | 3/30 (10.0%) | 21/36 (58.3%) P<0.001 | 25/40 (62.5%) P<0.001 |
| Median HAQ-DI Change from Baseline (min, max) | |||
| Overall | 0.00 (-0.13, 0.13) | -0.13 (-0.38, 0.00) P=0.01 | -0.25 (-0.50, 0.00) P=0.001 |
| Previous anti-TNF agent | 0.00 (-1.0, 0.9) | -0.13 (-1.8, 1.0) P=0.018 | -0.19 (-1.9, 1.5) P=0.012 |
| Anti-TNF agent naïve | 0.00 (-1.3, 1.0) | -0.25 (-1.5, 0.8) P=0.034 | -0.25 (-1.4, 0.6) P=0.018 |
| Abbreviations: ACR20, 50, and 70, ≥20%, ≥50%, and ≥70% improvement in American College of Rheumatology criteria from baseline; HAQ-DI, health assessment questionnaire disability index; PASI 75, ≥75% improvement in Psoriasis Area and Severity Index; PBO, placebo. aAmong patients with ≥3% BSA psoriasis involvement at baseline. | |||
Median percent improvement in the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) among patients with enthesitis at baseline (n=221) were 33.3%, 48.3%, and 0.0% for the STELARA 45-mg (not statistically significant), STELARA 90-mg (P<0.01), and placebo groups, respectively. - Among patients with dactylitis at baseline (n=127), the median percent improvement in dactylitis scores were 0.0%, 65.0%, and 0.0% for patients in the STELARA 45-mg, STELARA 90-mg, and placebo groups, respectively (not statistically significant).
A significantly greater percentage of patients treated with STELARA 45 mg and 90 mg achieved a DAS28-CRP EULAR response compared to placebo-treated patients; 54.4% (56/103) and 53.3% (56/105) vs 29.8% (21/104), respectively (P<0.001 for both STELARA doses vs placebo). - As shown in Table: Summary of Efficacy Among Randomized Patients in PSUMMIT II at Week 52, treatment with STELARA was generally more efficacious in patients who had not previously received an anti-TNF agent.
| PBO→ STELARA 45 mg | STELARA 45 mg | STELARA 90 mg | |
|---|---|---|---|
| ACR20 | |||
| Overall | 43/77 (55.8%) | 44/94 (46.8%) | 46/95 (48.4%) |
| Previous anti-TNF agent | 16/40 (40.0%) | 20/54 (37.0%) | 22/54 (40.7%) |
| Anti-TNF agent naïve | 27/37 (73.0%) | 24/40 (60.0%) | 24/41 (58.5%) |
| ACR50 | |||
| Overall | 22/77 (28.6%) | 26/94 (27.7%) | 25/95 (26.3%) |
| Previous anti-TNF agent | 7/40 (17.5%) | 10/54 (18.5%) | 11/54 (20.4%) |
| Anti-TNF agent naïve | 15/37 (40.5%) | 16/40 (40.0%) | 14/41 (34.1%) |
| ACR70 | |||
| Overall | 12/77 (15.6%) | 12/94 (12.8%) | 17/95 (17.9%) |
| Previous anti-TNF agent | 2/40 (12.5%) | 3/54 (5.6%) | 4/54 (7.4%) |
| Anti-TNF agent naïve | 7/37 (18.9%) | 9/40 (22.5%) | 13/41 (31.7%) |
| ACR20 by number of prior anti-TNF agents | |||
| 1 | 12/22 (54.5%) | 11/21 (52.4%) | 14/28 (50.0%) |
| >1 | 4/18 (22.5%) | 9/33 (27.3%) | 8/26 (30.8%) |
| PASI 75c | |||
| Overall | 32/57 (56.1%) | 39/69 (56.5%) | 47/73 (64.4%) |
| Previous anti-TNF agent | 13/30 (43.3%) | 13/36 (36.1%) | 20/40 (50.0%) |
| Anti-TNF agent naïve | 19/27 (70.4%) | 26/33 (78.8%) | 27/33 (81.8%) |
| Median HAQ-DI Change from Baseline | |||
| Overall | n=77 -0.1 (-0.5, 0.0) | n=94 -0.3 (-0.5, 0.0) | n=95 -0.3 (-0.5, 0.0) |
| Previous anti-TNF agent | n=40 0.00 (-0.13, 0.13) | n=54 -0.13 (-0.50, 0.00) | n=54 -0.13 (-0.50, 0.00) |
| Anti-TNF agent naïve | n=37 -0.38 (-0.63, 0.00) | n=40 -0.25 (-0.44, 0.00) | n=41 0.36 (-0.50, 0.00) |
| Median % improvement (IQR) in enthesitisa | |||
| n=53 -33.3 (-100.0, 0.0) | n=66 -36.7 (-87.5, 0.0) | n=71 -60.0 (-100.0, 0.0) | |
| Median % improvement (IQR) in dactylitisb | |||
| n=24 -100.0 (-100.0, -33.3) | n=44 -95.0 (-100.0, 0.0) | n=38 -90.9 (-100.0, 0.0) | |
| DAS28-CRP/EULAR responsed | |||
| 53/77 (68.8%) | 56/94 (59.6%) | 59/95 (62.1%) | |
| Abbreviations: ACR20, 50, and 70, ≥20%, ≥50%, and ≥70% improvement in American College of Rheumatology criteria from baseline; DAS28-CRP, 28-joint disease activity score based on C-reactive protein; EULAR, European League Against Rheumatism; HAQ-DI, health assessment questionnaire disability index; IQR, interquartile range; PASI 75, ≥75% improvement in Psoriasis Area and Severity Index; PBO, placebo. aAmong patients with enthesitis at baseline (PsA modified MASES score ≥1). bAmong patients with ≥1 dactylitis digit at baseline. cAmong patients with ≥3% BSA psoriasis involvement at baseline. dA good or moderate DAS28-CRP response. | |||
Through week 16, the number of patients with ≥1 AE was 63.1% (65/103), 60.6% (63/104), 54.8% (57/104) for the STELARA 45-mg, STELARA 90-mg, and placebo groups, respectively. - Serious AEs were reported in 0.0%, 1.0% (1/104), and 4.8% (5/104), in the STELARA 45-mg, STELARA 90-mg, and placebo groups, respectively.
- Investigator-reported infections were reported in 29.1% (30/103), 25% (26/104), and 24% (25/104) of patients in the STELARA 45-mg, STELARA 90-mg, and placebo groups, respectively.
- One serious infection was reported in a placebo-treated patient and none were reported in STELARA -treated patients.
- No cases of malignancy or MACE occurred during the placebo-controlled period.
- Through week 60, AEs occurred in 55% (44/80), 78.6% (81/103), and 77.9% (81/104) of patients in the placebo→STELARA 45-mg, STELARA 45-mg and 90-mg groups, respectively.
- Serious AEs occurred in 3.8% (3/80) of patients in the placebo→STELARA 45-mg group, in 5.8% (6/103) of patients in the STELARA 45-mg group, and in 5.8% (6/104) of patients in the STELARA 90-mg group.
- In STELARA-treated patients, serious AEs occurred in 3.4% of patients treated with MTX and in 7.1% of patients not treated with MTX.
- Two patients treated with STELARA 90 mg reported a serious infection (rate=0.74/100 patient-years [PY]).
- Two patients developed malignancies. One patient with breast cancer occurring in the placebo→STELARA 45-mg group and another with squamous cell carcinoma in situ in an area of cleared skin plaque in the STELARA 90-mg group. Both patients had previously been treated with an anti-TNF agent.
- There were 3 MACE reported in 2 patients receiving STELARA 45 mg and in 1 patient receiving STELARA 90 mg. Two events were classified as myocardial infarctions (rate=0.74/100 PY). All 3 patients had multiple cardiovascular risk factors (history of stroke, hypertension, smoking, and/or symptoms of metabolic syndrome) and a history of treatment with anti-TNF agents.
- There were no cases of tuberculosis (TB) reported, and no patients died in this study.
- The overall rates of AEs were comparable between placebo and STELARA treatment groups during the placebo-controlled period.
- Overall AE rates were not impacted by baseline MTX use or prior treatment with an anti-TNF agent.
- There were no cases of active TB, serious opportunistic infections, reversible posterior leukoencephalopathy syndrome (RPLS), demyelination, anaphylaxis, or serum sickness-like reactions.
| PBO→ STELARA 45 mg | STELARA 45 mg | STELARA 90 mg | Combined | |
|---|---|---|---|---|
| Patients treated with STELARA (n)a | 269 | 308 | 308 | 885 |
| Total PY | 348 | 489 | 491 | 1327 |
| AEs, rates/100 PY (95% CI) | 133.95 (122.06, 146.68) | 217.85 (204.96, 231.34) | 202.00 (189.62, 214.98) | 190.00 (182.66, 197.57) |
| Infections | 45.42 (38.61, 53.07) | 61.57 (54.81, 68.94) | 66.45 (59.43, 74.07) | 59.14 (55.08, 63.43) |
| SAEs, rates/100 PY (95% CI) | 6.32 (3.96, 9.57) | 8.18 (5.85, 11.14) | 9.17 (6.69, 12.27) | 8.06 (6.61, 9.74) |
| Deaths | 0 | 0 | 0 | 0 |
| AEs leading to discontinuationb | 1.44 (0.47, 3.36) | 3.51 (2.04, 5.62) | 2.46 (1.27, 4.30) | 2.58 (1.78, 3.60) |
| Abbreviations: AEs, adverse events; CI, confidence interval; PBO, placebo; PY, patient-years; SAEs, serious adverse events. aOnly STELARA exposure period was included. bDiscontinuation analyses were patient-level, whereby patients who discontinued due to 1 or more AEs were counted only once. Therefore, the total PY of follow-up is slightly lower than the follow-up displayed | ||||
Pooled data from the phase 2 study of STELARA in 146 patients with active PsA (12 week placebo-controlled period and 36 total weeks of follow up) were included for AEs of interest described in Table: Phase 2, PSUMMIT I & II AEs of Interest Through 2 Years.
Phase 2, PSUMMIT I & II AEs of Interest Through 2 Years6
| PBO→ STELARA 45 mg | STELARA 45 mg | STELARA 90 mg | Combined | |
|---|---|---|---|---|
| Patients treated (n)a,b | 379 | 577 | 497 | 1018 |
| Total PY | 145 | 773 | 631 | 1403 |
| Events of interest, rates/100 PY (95% CI)c | ||||
| Serious infections | 0.69 (0.02, 3.84) | 0.52 (0.14, 1.33) | 2.06 (1.10, 3.52) | 1.21 (0.71, 1.94) |
| NMSC | 0.00 (0.00, 2.07) | 0.00 (0.00, 0.39) | 0.64 (0.17, 1.63) | 0.29 (0.08, 0.73) |
| Malignancy other than NMSC | 0.00 (0.00, 2.07) | 0.39 (0.08, 1.14) | 0.00 (0.00, 0.47) | 0.21 (0.04, 0.63) |
| MACE | 0.69 (0.02, 3.84) | 1.04 (0.45, 2.04) | 0.32 (0.04, 1.15) | 0.71 (0.34, 1.31) |
| Abbreviations: CI, confidence interval; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PBO, placebo; PY, patient-years. aPsA studies include phase 2 and phase 3 – PSUMMIT I & II. bPlacebo early escaped and crossover patients were included in the STELARA column (45 mg column) after early escape at week 16 or crossover at week 24. Patients who were dose escalated from 45 mg to 90 mg were included in the 90 mg column following dose escalation. cConfidence intervals based on an exact method assuming that the observed number of events follows a Poisson distribution. | ||||
A literature search of MEDLINE®
References
| 1 | McInnes IB, Kavanaugh A, Gottlieb AB, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013;382(9894):780-789. |
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