Table 2.

Studies of ustekinumab in the literature

	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	45 mg SC × 1 90 mg SC × 1 45 mg SC every week for 4 weeks 90 mg SC every week for 4 weeks Placebo	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	45 mg or 90 mg SC at weeks 0 and 4 and then every 12 weeks Placebo SC at weeks 0 and 4, with subsequent crossover to medication at week 12 Patients who were initially randomized to receive medication at week 0 and achieved PASI 75 at weeks 28 and 40 were re-randomized at week 40 to maintenance dosage or withdrawal from treatment until loss of response	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	45 mg or 90 mg SC at weeks 0 and 4 then every 12 weeks Placebo SC at weeks 0 and 4 then every 12 weeks Partial responders (ie, patients achieving ≥ PASI 50 but < PASI 75 from baseline were re-randomized at week 28 to continue dosing every 12 weeks or escalate to dosing every 8 weeks	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	90 mg or 63 mg SC every week for 4 weeks followed by placebo at weeks 12 and 16 (Group 1) Placebo SC every week for 4 weeks followed by 63 mg SC at weeks 12 and 16 (Group 2)	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: SC placebo weekly at weeks 0–3 then 90 mg at weeks 8–11 SC 90 mg weekly at weeks 0–3 then placebo at weeks 8–11 IV placebo at week 0 then 4.5 mg/kg at week 8 IV 4.5 mg/kg at week 0 then placebo at week 8 Population 2: SC 90 mg weekly at weeks 0–3 IV 4.5 mg/kg at week 0	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	Placebo SC every 4 weeks 27 mg SC every 4 week 90 mg SC every 4 weeks 180 mg SC every 4 weeks 90 mg SC every 8 weeks with placebo given at weeks 7 and 15	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.