ACR: Humira Shows 'Profound' Benefit for Kids With Rheumatoid Arthritis

WASHINGTON, Nov. 13 -- Humira (adalimumab) has a "quite profound" benefit for children with juvenile rheumatoid arthritis and is well-tolerated, a researcher reported here.

The finding was based on a prospective 48-week clinical trial and 88 weeks of an extension study, according to Daniel Lovell, M.D., of the Cincinnati Children's Hospital Medical Center. The results mean "we can now make the disease almost a non-issue" for children.

Some benefit was expected, because the drug is approved for rheumatoid arthritis in adults, but the magnitude and speed of action was a surprise, Dr. Lovell told a press conference at the American College of Rheumatology meeting.

He said more than one in five children in the study "for the first time ever" achieved a benefit of ACR Ped 90 - meaning that of six elements of the disease deemed important for children by the ACR, at least three improved by more than 90%.

The study, involving 171 children aged four to 17, began with a 16-week open-label phase, in which all children were given the drug, an immunosuppressant that blocks the action of tumor necrosis factor-alpha.

During this phase, 83% of children achieved an ACR Ped 30 result, which is the usual measure of response to a drug for children with this disease, Dr. Lovell said.

At the same time, however, 52% met the criteria for an ACR Ped 70 result, which he said was "an extraordinarily robust degree of improvement."

"To put it in common usage," Dr. Lovell said, "if you have an ACR 70, there are only a few days a month when you even remember you have arthritis."

Children with an ACR Ped 30 response moved on to the blinded phase of the trial, in which they were divided into those on a background of methotrexate and those not taking the older drug, and randomized to either Humira or placebo.

The primary endpoint was the rate of flare-ups of the arthritis, Dr. Lovell said. The researchers found:

• Among those not taking methotrexate, 71% of those on placebo experienced a flare, compared to 43% of those on Humira.
• Among those taking methotrexate, 65% of those on placebo had a flare-up, compared with 37% of those getting Humira.
• The differences were statistically significant at P=0.03 and P=0.01, respectively.

Adverse effects were mainly mild upper respiratory infections, he said.

Patients on placebo came out of the trial when they experienced a flare and were entered into the extension study on Humira, while the remaining patients entered the extension when the double-blind phase ended, he said.

During the extension, Dr. Lovell said, 80% of the patients reached an ACR Ped 30 level and 70% reached ACR Ped 70.

"These kids continued to show the benefit," he said.

The results are "extremely promising," commented Stanley Cohen, M.D., of the University of Texas Southwestern Medical Center at Dallas, who was not involved with the study. With these biologics, he said "we are in a whole new era" of treatment for juvenile arthritis, he added.

"We used to have rehab centers with kids in wheelchairs," Dr. Cohen said. Those are gone because of new medications such as methotrexate. The next generation of targeted treatments, such as Humira, means "those crippled children hat we used to see will be gone. It will be a rare, rare patient who gets to that stage."

The problem now facing clinicians, he said, is that several biologic therapies are in development and there is little guidance as to which medications should be used in which cases.

Dr. Lovell reported receiving consulting fees from Amgen, Centocor, Bristol Myers Squibb, Abbott, Regeneron, Xoma, Hoffman-La Roche, and Novartis. The drug is marketed by Abbott Laboratories.