Responses to Ustekinumab in PsA Significant and Sustained

BOSTON — Inhibition of two key immunoregulatory cytokines known to be involved in the pathogenesis of psoriasis and other autoimmune diseases led to significant improvements in psoriatic arthritis, judging from data from a new study, Dr. Alice B. Gottlieb reported at the annual meeting of the American College of Rheumatology.

Interleukin (IL)-12 and IL-23 play important roles in coordinating innate and adaptive immune responses, binding via the p40 subunit to the IL-12 receptor β1 on the surface of T cells and natural killer cells. Among the functions of IL-12 in psoriasis are T-cell differentiation and the facilitation of T-cell homing to the skin (Cell Immunol. 2007;247:1-11).

The drug ustekinumab now has also been evaluated in active psoriatic arthritis (PsA) in a multicenter, double-blind study that included 146 patients randomized to receive the active treatment at weeks 0, 1, 2, and 3, followed by placebo at weeks 12 and 16, or placebo at weeks 0, 1, 2, and 3 followed by the active treatment at weeks 12 and 16. They were then followed through week 36.

The primary end point was the percentage of patients achieving a response on the American College of Rheumatology (ACR) 20 scale at week 12. Patients in the active treatment group received four subcutaneous doses of either 63 mg (n = 59) or 90 mg (n = 17) of ustekinumab. This inconsistency in dose resulted from a change in preparation of the drug during the study, said Dr. Gottlieb, of the Tufts-New England Medical Center, Boston.

At baseline, the swollen joint count was 12, and the tender joint count was 22. Approximately 20% of patients were on concurrent methotrexate, and half were on concurrent NSAIDs, but none was taking oral corticosteroids. At week 12, 42% of patients in the ustekinumab group had achieved the primary end point, compared with 14% of patients in the placebo group.

By week 36, patients initially randomized to ustekinumab had not received any active treatment for 32 week—yet three-quarters maintained an ACR 20 response. “You do not see this with any of the anti-[tumor necrosis factor] agents,” Dr. Gottlieb said.

Moreover, patients who initially received placebo but then were crossed over to the active treatment group at week 12 also went on to have rapid and sustained responses, she said.

A higher proportion of patients in the active treatment group also reached ACR 50 and ACR 70 responses. A total of 25% and 11% of patients in the ustekinumab achieved these levels of response, compared with 7% and 0% of those in the placebo group.

The decrease from baseline on the Health Assessment Questionnaire disability index at week 12 was greater in the ustekinumab group (mean change −0.31), compared with the placebo group (−0.04).

A total of 52% of patients receiving the active treatment achieved a PASI 75 result at week 12, as did 6% of those receiving placebo. The 85% of patients with at least 3% body surface area psoriasis involvement who received ustekinumab had a greater decrease in the Dermatology Life Quality Index (mean change −8.6), compared with those who received placebo (−0.8). All of these differences were statistically significant.

There were no serious adverse events through week 12 in the active treatment group, whereas in the placebo group there was one report of myocardial infarction, one of gastric ulcer hemorrhage, and one of chest pain. There were no problems with abnormal laboratory values through week 12, nor were there any cases of tuberculosis or serious opportunistic infections, she said.

Dr. Gottlieb disclosed that she has received research grants and consulting fees from Centocor Research and Development Inc., which funded the trial and makes ustekinumab.

BOSTON — Inhibition of two key immunoregulatory cytokines known to be involved in the pathogenesis of psoriasis and other autoimmune diseases led to significant improvements in psoriatic arthritis, judging from data from a new study, Dr. Alice B. Gottlieb reported at the annual meeting of the American College of Rheumatology.

Interleukin (IL)-12 and IL-23 play important roles in coordinating innate and adaptive immune responses, binding via the p40 subunit to the IL-12 receptor β1 on the surface of T cells and natural killer cells. Among the functions of IL-12 in psoriasis are T-cell differentiation and the facilitation of T-cell homing to the skin (Cell Immunol. 2007;247:1-11).

The drug ustekinumab now has also been evaluated in active psoriatic arthritis (PsA) in a multicenter, double-blind study that included 146 patients randomized to receive the active treatment at weeks 0, 1, 2, and 3, followed by placebo at weeks 12 and 16, or placebo at weeks 0, 1, 2, and 3 followed by the active treatment at weeks 12 and 16. They were then followed through week 36.

The primary end point was the percentage of patients achieving a response on the American College of Rheumatology (ACR) 20 scale at week 12. Patients in the active treatment group received four subcutaneous doses of either 63 mg (n = 59) or 90 mg (n = 17) of ustekinumab. This inconsistency in dose resulted from a change in preparation of the drug during the study, said Dr. Gottlieb, of the Tufts-New England Medical Center, Boston.

At baseline, the swollen joint count was 12, and the tender joint count was 22. Approximately 20% of patients were on concurrent methotrexate, and half were on concurrent NSAIDs, but none was taking oral corticosteroids. At week 12, 42% of patients in the ustekinumab group had achieved the primary end point, compared with 14% of patients in the placebo group.

By week 36, patients initially randomized to ustekinumab had not received any active treatment for 32 week—yet three-quarters maintained an ACR 20 response. “You do not see this with any of the anti-[tumor necrosis factor] agents,” Dr. Gottlieb said.

Moreover, patients who initially received placebo but then were crossed over to the active treatment group at week 12 also went on to have rapid and sustained responses, she said.

A higher proportion of patients in the active treatment group also reached ACR 50 and ACR 70 responses. A total of 25% and 11% of patients in the ustekinumab achieved these levels of response, compared with 7% and 0% of those in the placebo group.

The decrease from baseline on the Health Assessment Questionnaire disability index at week 12 was greater in the ustekinumab group (mean change −0.31), compared with the placebo group (−0.04).

A total of 52% of patients receiving the active treatment achieved a PASI 75 result at week 12, as did 6% of those receiving placebo. The 85% of patients with at least 3% body surface area psoriasis involvement who received ustekinumab had a greater decrease in the Dermatology Life Quality Index (mean change −8.6), compared with those who received placebo (−0.8). All of these differences were statistically significant.

There were no serious adverse events through week 12 in the active treatment group, whereas in the placebo group there was one report of myocardial infarction, one of gastric ulcer hemorrhage, and one of chest pain. There were no problems with abnormal laboratory values through week 12, nor were there any cases of tuberculosis or serious opportunistic infections, she said.

Dr. Gottlieb disclosed that she has received research grants and consulting fees from Centocor Research and Development Inc., which funded the trial and makes ustekinumab.

BOSTON — Inhibition of two key immunoregulatory cytokines known to be involved in the pathogenesis of psoriasis and other autoimmune diseases led to significant improvements in psoriatic arthritis, judging from data from a new study, Dr. Alice B. Gottlieb reported at the annual meeting of the American College of Rheumatology.

Interleukin (IL)-12 and IL-23 play important roles in coordinating innate and adaptive immune responses, binding via the p40 subunit to the IL-12 receptor β1 on the surface of T cells and natural killer cells. Among the functions of IL-12 in psoriasis are T-cell differentiation and the facilitation of T-cell homing to the skin (Cell Immunol. 2007;247:1-11).

The drug ustekinumab now has also been evaluated in active psoriatic arthritis (PsA) in a multicenter, double-blind study that included 146 patients randomized to receive the active treatment at weeks 0, 1, 2, and 3, followed by placebo at weeks 12 and 16, or placebo at weeks 0, 1, 2, and 3 followed by the active treatment at weeks 12 and 16. They were then followed through week 36.

The primary end point was the percentage of patients achieving a response on the American College of Rheumatology (ACR) 20 scale at week 12. Patients in the active treatment group received four subcutaneous doses of either 63 mg (n = 59) or 90 mg (n = 17) of ustekinumab. This inconsistency in dose resulted from a change in preparation of the drug during the study, said Dr. Gottlieb, of the Tufts-New England Medical Center, Boston.

At baseline, the swollen joint count was 12, and the tender joint count was 22. Approximately 20% of patients were on concurrent methotrexate, and half were on concurrent NSAIDs, but none was taking oral corticosteroids. At week 12, 42% of patients in the ustekinumab group had achieved the primary end point, compared with 14% of patients in the placebo group.

By week 36, patients initially randomized to ustekinumab had not received any active treatment for 32 week—yet three-quarters maintained an ACR 20 response. “You do not see this with any of the anti-[tumor necrosis factor] agents,” Dr. Gottlieb said.

Moreover, patients who initially received placebo but then were crossed over to the active treatment group at week 12 also went on to have rapid and sustained responses, she said.

A higher proportion of patients in the active treatment group also reached ACR 50 and ACR 70 responses. A total of 25% and 11% of patients in the ustekinumab achieved these levels of response, compared with 7% and 0% of those in the placebo group.

The decrease from baseline on the Health Assessment Questionnaire disability index at week 12 was greater in the ustekinumab group (mean change −0.31), compared with the placebo group (−0.04).

A total of 52% of patients receiving the active treatment achieved a PASI 75 result at week 12, as did 6% of those receiving placebo. The 85% of patients with at least 3% body surface area psoriasis involvement who received ustekinumab had a greater decrease in the Dermatology Life Quality Index (mean change −8.6), compared with those who received placebo (−0.8). All of these differences were statistically significant.

There were no serious adverse events through week 12 in the active treatment group, whereas in the placebo group there was one report of myocardial infarction, one of gastric ulcer hemorrhage, and one of chest pain. There were no problems with abnormal laboratory values through week 12, nor were there any cases of tuberculosis or serious opportunistic infections, she said.

Dr. Gottlieb disclosed that she has received research grants and consulting fees from Centocor Research and Development Inc., which funded the trial and makes ustekinumab.