Table 2.
Study title | Total number of patients | Dosages studied | Primary results | Conclusions | |
---|---|---|---|---|---|
Psoriasis | |||||
Phase I | |||||
A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis36 | 18 | 4 dose cohorts: 0.1, 0.3, 1.0, and 5.0 mg per kg IV | 12 of 18 subjects (67%) achieved at least a PASI 75 | Significant and sustained concentration-dependent improvements in psoriatic lesions were observed in most subjects | |
A phase 1, double-blind, placebo-controlled study evaluating single subcutaneous administrations of a human interleukin-12/23 monoclonal antibody in subjects with plaque psoriasis38 | 21 | 4 dose cohorts: 0.27, 0.675, 1.35, and 2.7 mg/kg SC | 13 of 17 subjects (76%) achieved at least a PASI 75 | A single SC administration of IL-12/23 monoclonal antibody was well tolerated and showed clinical response in subjects with moderate-to-severe psoriasis | |
Phase II | |||||
A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis39 | 320 |
|
At week 12: PASI 75 seen in 52% of patients who received single 45 mg dose, in 59% who received single 90 mg dose, in 67% of those who received four weekly 45 mg doses, and in 81% of those who received four weekly 90 mg doses | This study demonstrates the therapeutic efficacy of an interleukin-12/23 monoclonal antibody in psoriasis and provides further evidence of a role of the interleukin-12/23 p40 cytokines in the pathophysiology of psoriasis. | |
Phase III | |||||
Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomized, double-blind, placebo-controlled trial (PHOENIX 1)40 | 766 |
|
67.1% of patients in 45 mg group and 66.4% in 90 mg group versus 3.1% in placebo group achieved PASI 75 at week 12 | Ustekinumab seems to be efficacious for the treatment of moderate-to-severe psoriasis; dosing every 12 weeks maintains efficacy for at least a year in most patients | |
Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomized, double-blind, placebo-controlled trial (PHOENIX 2)41 | 1230 |
|
66.7% of patients receiving 45 mg and 75.7% receiving 90 mg versus 3.7% in placebo achieved PASI 75 at week 12; Of those re-randomized at week 28, 68.8% who received 90 mg every 8 weeks versus 33.3% of those who continued the same dose at every 12 weeks achieved PASI 75 at week 52 | Although treatment with ustekinumab every 12 weeks is effective for most patients with moderate-to-severe psoriasis, intensification of dosing to once every 8 weeks with 90 mg might be necessary to elicit a full response in patients who only partially respond to the initial regimen | |
Psoriatic arthritis | |||||
Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomized, double-blind, placebo-controlled, crossover trial11 | 146 |
|
42.0 % in Group 1 versus 14.0 % in Group 2 achieved an ACR20 at week 12 | Ustekinumab was well tolerated and significantly reduced the signs and symptoms of psoriatic arthritis along with diminishing skin lesions compared with placebo; Larger and longer term studies are needed to further characterize the efficacy and safety for the treatment of psoriatic arthritis | |
Crohn’s disease | |||||
A randomized trial of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn’s disease47 | 104 |
Population 1:
|
53% of the combined groups given ustekinumab versus 30% in the placebo achieved at least a 25% and 70 point reduction in the CDAI score at weeks 4 and 6 and 49% versus 40% respectively at week 8 | Ustekinumab induced a clinical response in patients with moderate-to-severe Crohn’s disease, especially in patients previously given infliximab | |
Multiple sclerosis | |||||
Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomized, dose-ranging study48 | 249 |
|
There was no significant reduction in the cumulative number of new Gadolinium-enhancing T1-weighted lesions on serial cranial MRI through week 23 for any of the ustekinumab dosage groups versus placebo | Ustekinumab is generally well tolerated, but does not show efficacy in reducing the cumulative number of gadolinium-enhancing T1-weighted lesions in multiple sclerosis |
Abbreviations: IV, intravenous; SC, subcutaneous; IL, interleukin; mg, milligrams; PASI 75, at least a 75% improvement in the psoriasis area and severity index; ACR, American College of Rheumatology core set measures; CDAI, Crohn’s Disease Activity Index; MRI, magnetic resonance imaging; kg, kilogram.