Table 1.
Overview of RCTs included in integrated ustekinumab safety analyses
| Study phase/identifier (dates) | Treatment groups/numbers of patients |
|---|---|
| Moderate-to-severe plaque psoriasis (no concomitant CSs/IMMs) | |
| Phase II/ NCT00320216 (11/2003–3/2005) [23] |
Placebo weekly × 4 SC doses (n = 64)a |
| Ustekinumab 45 mg single SC dose—week 0 (n = 64) | |
| Ustekinumab 90 mg single SC dose—week 0 (n = 64) | |
| Ustekinumab 45 mg weekly × 4 SC doses (n = 64) | |
| Ustekinumab 90 mg weekly × 4 SC doses (n = 64) | |
| Phase III/PHOENIX-1 NCT00267969 (12/2005–5/2011) [5] |
Placebo SC (weeks 0 and 4) → ustekinumab 45 mg SC—weeks 12 and 16 then q12w (n = 123) |
| Placebo SC (weeks 0 and 4) → ustekinumab 90 mg SC—weeks 12 and 16 then q12w (n = 120) | |
| Ustekinumab 45 mg SC—weeks 0 and 4 then q12w (n = 255) | |
| Ustekinumab 90 mg SC—weeks 0 and 4 then q12w (n = 256) | |
| At week 28, PASI75 responders continued 45 or 90 mg, q12w; PASI50–75 partial responders switched to 45 or 90 mg q8w | |
| At week 40, PASI75 responders initially randomized to ustekinumab were re-randomized to placebo or 45/90 mg q12w; PASI75 responders initially randomized to placebo withdrew from treatment; PASI75 partial responders initially randomized to placebo switched from q12w → q8w dosing | |
| Phase III/PHOENIX-2 NCT00307437 (5/2005–10/2011) [6] |
Placebo SC (weeks 0 and 4) → ustekinumab 45 mg SC—weeks 12 and 16 then q12w (n = 197) |
| Placebo SC (weeks 0 and 4) → ustekinumab 90 mg SC—weeks 12 and 16 then q12w (n = 195) | |
| Ustekinumab 45 mg SC—weeks 0 and 4 then q12w (n = 409) | |
| Ustekinumab 90 mg SC—weeks 0 and 4 then q12w (n = 411) | |
| At week 28, PASI50–75 partial responders were randomized to maintain their originally assigned dose (45 or 90 mg) at q12w intervals or dose-adjusted to q8w | |
| Phase III/ACCEPT NCT00454584 (3/2007–1/2009) [7] |
Etanercept 50 mg SC twice weekly for 12 weeks (n = 347)b |
| Ustekinumab 45 mg SC—weeks 0 and 4 (n = 209)b | |
| Ustekinumab 90 mg SC—weeks 0 and 4 (n = 347)b | |
| Active psoriatic arthritis (with or without CSs/MTX) | |
| Phase II/ NCT00267956 (12/2005–9/2007) [24] |
Placebo SC—weeks 0, 1, 2, and 3 → ustekinumab 90 mg SC—weeks 12 and 16 (n = 70) |
| Ustekinumab 90 mg SC—weeks 0, 1, 2, and 3 → placebo SC—weeks 12 and 16 (n = 76) | |
| Inclusion of up to 25% of patients previously treated with anti-TNF agents allowed | |
| Phase III/PSUMMIT-1 NCT01009086 (12/2009–5/2013) [8] |
Placebo SC—weeks 0, 4, 16, and 20) → ustekinumab 45 mg SC—weeks 24 and 28 then q12w (n = 206) |
| Ustekinumab 45 mg SC—weeks 0 and 4 then q12w (n = 205) | |
| Ustekinumab 90 mg SC—weeks 0 and 4 then q12w (n = 204) | |
| Naïve to anti-TNF agents | |
| Phase III/PSUMMIT-2 NCT01077362 (3/2010–11/2012) [9] |
Placebo SC—weeks 0, 4, 16, and 20 → ustekinumab 45 mg SC—weeks 24 and 28 then q12w (n = 104) |
| Ustekinumab 45 mg SC—weeks 0 and 4 then q12w (n = 103) | |
| Ustekinumab 90 mg SC—weeks 0 and 4 then q12w (n = 105) | |
| Inclusion of 50–60% of patients previously treated with anti-TNF agents allowed | |
| Moderately-to-severely active Crohn’s Disease (with or without concomitant CSs/IMMs) | |
| Phase IIa NCT00265122 (4/2004–10/2006) [21] |
Population 1—active disease despite treatment with conventional therapy (n = 104): |
| Ustekinumab 90 mg SC—weeks 0, 1, 2 and 3; placebo SC—weeks 8, 9, 10, and 11 (n = 25) | |
| Placebo SC—weeks 0, 1, 2, and 3; ustekinumab 90 mg SC—weeks 8, 9, 10, and 11 (n = 26) | |
| Ustekinumab 4.5 mg/kg IV—week 0; placebo IV—week 8 (n = 26) | |
| Placebo IV—week 0; ustekinumab 4.5 mg/kg IV—week 8 (n = 27) | |
| Population 2—failure to respond to, or loss of response to, infliximab at the maximum approved dose and treatment regimen for CD (n = 27): | |
| Ustekinumab 90 mg SC—weeks 0, 1, 2, and 3 (n = 14) | |
| Ustekinumab 4.5 mg/kg IV—week 0 (n = 13) | |
| Phase IIb/CERTIFI NCT00771667 (12/2008–12/2010) [22] |
Randomized IV induction phase: |
| Placebo (n = 132); ustekinumab 1 mg/kg (n = 131); ustekinumab 3 mg/kg (n = 132); ustekinumab 6 mg/kg (n = 131) | |
| SC maintenance phase (based on clinical response to IV induction at week 6): | |
| Responders—randomized to: placebo—weeks 8 and 16 (n = 73); ustekinumab 90 mg SC—weeks 8 and 16 (n = 72) | |
| Non-responders—randomized to: ustekinumab 90 mg SC (n = 109); placebo (n = 110) | |
| Non-randomized patients (n = 113): placebo—weeks 8 and 16 (responders to placebo IV induction, n = 28); Ustekinumab 270 mg SC—week 8, and 90 mg SC—week 16 (non-responders to placebo IV induction, n = 85) | |
| Patients who did not respond initially, responded initially but then lost response, or were intolerant of prior infliximab, adalimumab, or certolizumab pegol | |
| Phase III/UNITI-1 NCT01369329 (7/2011–7/2013) [11] |
Single IV induction dose at week 0 (n = 741; 769 totalc): placebo (n = 247); ustekinumab 130 mg (n = 245); tiered (weight-based) ustekinumab doses approximately 6 mg/kg (n = 249) |
| Patients who did not respond initially, responded initially but then lost response, or were intolerant of prior infliximab, adalimumab, or certolizumab pegol | |
| Phase III/UNITI-2 NCT01369342 (7/2011–10/2014) [11] |
Single IV induction dose at week 0 (n = 628; 640 totald): |
| Placebo (n = 210); ustekinumab 130 mg (n = 209); tiered ustekinumab doses approximately 6 mg/kg (n = 209) | |
| Patients had active inflammation and demonstration of inadequate response to, or failure to tolerate, CSs/IMMs; patients with CS dependence and who received but did not fail a TNF antagonist were allowed | |
| Phase III/IM-UNITI NCT01369355 (9/2011–10/2019) [11] |
Randomized (responders to ustekinumab IV induction, n = 397): |
| Placebo SC (n = 133);e ustekinumab 90 mg SC q12w (n = 132); ustekinumab 90 mg SC q8w (n = 132) | |
| Non-randomized (n = 884): | |
| Placebo SC (responders to placebo IV induction, n = 123) | |
| Non-responders to ustekinumab IV induction (n = 476): ustekinumab 90 mg SC week 0 → discontinued at week 8 (n = 221); ustekinumab 90 mg SC week 0 → 90 mg SC q8w (n = 255) | |
| Non-responders to placebo IV induction (n = 285): ustekinumab 130 mg IV—week 0 → discontinued at week 8 (n = 121); ustekinumab 130 mg IV—week 0 → 90 mg SC q12w (n = 164) | |
| Patients from both phase III induction studies could continue into this maintenance study, with the primary population comprising responders to IV ustekinumab induction therapy | |
CD Crohn’s disease, CSs corticosteroids, IMMs immunomodulators, IV intravenous, MTX methotrexate, PASI Psoriasis Area and Severity Index, PGA Physician’s Global Assessment, q8/12w every 8/12 weeks, RCT randomized controlled trial, SC subcutaneous, TNF tumor necrosis factor
aAt week 20, patients in the placebo group received a single dose of ustekinumab 90 mg SC
bTreatment after week 12 depended on PGA response at week 12 and initial treatment assignment (etanercept non-responders received ustekinumab 90 mg, ustekinumab non-responders received an additional ustekinumab dose at week 16, all responders had treatment interrupted followed by ustekinumab re-treatment if psoriasis recurred). Etanercept patients were not included in these analyses through week 12
c28 patients who received a previous IV formulation were excluded from the efficacy analyses and some safety analyses of the individual studies but were included in these integrated safety analyses
d12 patients who received a previous IV formulation were excluded from the efficacy analyses and some safety analyses of the individual studies but were included in these integrated safety analyses
eThose continuing placebo 16 weeks after IV ustekinumab induction were subsequently included in the placebo group for the 1-year analyses (unless/until they met loss of response criteria and crossed back to ustekinumab [38% of the 133 patients])