BOSTON, Massachusetts—The anti-IL 12/23 monoclonal antibody CNTO 1275 (ustekinumab, Centocor, Inc) produced dramatic improvements in psoriatic arthritis (PsA) that lasted for 32 weeks after treatment with only four injections of the drug, according to late-breaking phase II data reported by Alice B. Gottlieb, MD, PhD, at the 2007 American College of Rheumatology meeting.¹

Dr. Gottlieb, professor of dermatology at Tufts-New England Medical Center in Boston said, "Treatment with an anti-IL-12/23 monoclonal antibody improved arthritis, disability, and psoriasis. Seventy [percent] to 80% of ACR20 responders at week 12 maintained their response to week 36, having had no treatment whatsoever for 32 weeks."

The investigators recruited 146 PsA patients from dermatology practices. All joint assessments were carried out by rheumatologists, who recorded at baseline a mean swollen count of 12 and a mean tender joint count of 22.

Patients were randomized to two treatment groups. Group 1 patients received ustekinumab 1275 mg or 63 mg sc at weeks 0, 1, 2, and 3, followed by placebo at weeks 12 and 16 (n = 76). Group 2 patients received placebo at weeks 0, 1, 2, and 3, followed by ustekinumab 63 mg at weeks 12 and 16 (n = 70). Patients were allowed to continue stable doses of methotrexate, prednisone, or NSAIDs.

"Please note that in group 1, from the third week to the end of week 36, patients are on nothing," Dr. Gottlieb said.

The primary endpoint was ACR20 response, which was achieved by 42.1% of patients in the treatment group and 14.3% of patients in the placebo group (P <.001) at week 12. Significantly more patients in the treatment group had ACR50 responses (25.0% versus 7.1%, P =.004) and ACR 70 responses (10.5% versus 0%, P  = .005).

"In group 1, at week 36, which is 32 weeks after the last dose, three fourths of patients who were in ACR20 response at week 12 were still in ACR20," Dr. Gottlieb said. "You do not see this with any of the anti-TNFs." The ACR50 and ACR70 responses showed similar sustained effects. More patients discontinued treatment for either adverse events or unsatisfactory results in the placebo group, most due to worsening baseline disease during the placebo phase.

Group 2 patients were largely able to catch up after receiving ustekinumab at weeks 12 and 16, Dr. Gottlieb reported, "After the placebo crossover, a two-dose regimen produced similar results to those seen with the four-dose regimen [in group 1]. I care about that because in psoriasis, the phase III studies and data going to the FDA will be for a two-dose regimen. I think it will be great that we won't have to have a different dosing regimen for those with psoriatic arthritis."

The ustekinumab patients also had significantly greater improvement in Health Assessment Questionnaire (HAQ) scores at week 12 (-0.31 versus -0.04, P <.001). At week 12, the percentage of subjects with >e;0.3 clinically significant  improvement in HAQ was 47% by week 12 and 34% at week 36 (after 32 weeks without any treatment).

Psoriasis also improved. The percentage of subjects achieving a Psoriasis Area and Severity Index (PASI) 75% improvement at week 12 was 52.4% with ustekinumab versus 5.5% with placebo (P <.001). Adverse event rates were similar in both groups.

12-Week Results of Ustekinumab Versus Placebo for PsA

	Ustekinumab 90 or 63 mg sc, 3 doses	Placebo	P
ACR20	42.1%	14.3%	<.001
ACR50	25.0%	7.1%	.004
ACR70	10.5%	0.0%	.005

Adapted from Gottlieb AB, et al. American College of Rheumatology Meeting, 2007.¹

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