WASHINGTON -- FDA reviewers questioned the trial results supporting a new indication for the blockbuster arthritis drug adalimumab (Humira) in advance of an advisory committee meeting early next week.
The drug's manufacturer, North Chicago, Ill.'s AbbVie, is seeking to market the monoclonal antibody for active nonradiographic axial spondyloarthritis in adults with signs of inflammation by elevated CRP or MRI.
However, the 192-patient study enrolled a subgroup of patients with radiographic evidence of spondyloarthritis -- defined as having fulfilled modified New York Criteria for ankylosing spondylitis (AS), reviewers told members of the FDA's Arthritis Advisory Committee.
"A markedly higher proportion of patients in the AS subgroup responded to adalimumab treatment compared to placebo-treatment and skewed results for the overall group higher," reviewers said in .
In the study, patients were given either adalimumab or placebo, and after 12 weeks, patients taking adalimumab showed significant improvement over placebo, 36% versus 15% (P<0.001).
In a post-hoc breakdown of patients, combining confirmed and nonconfirmed nonradiographic axial spondyloarthritis would increase the treatment difference to 15%.
"Thus, although we cannot draw definitive conclusions, having AS patients in the study does appear to increase the apparent treatment effect of adalimumab in the overall study population," the FDA reviewers said.
They also called the data "suggestive and hypothesis-generating" at best. "Typically, such findings would be confirmed in the setting of at least one additional controlled trial where the population is prospectively defined."
The safety profile in the study is consistent with the known profile of adalimumab. When used for other indications for which it has already been approved, it carries a boxed warning for certain malignancies and infections.
Adalimumab first gained approval in December 2002 to treat rheumatoid arthritis. It has since been expanded for additional indications including psoriatic arthritis, ankylosing spondylitis, Crohn's disease, plaque psoriasis, and others. The drug is delivered subcutaneously every other week at 40 mg.
Members of the FDA's Arthritis Advisory Committee Tuesday morning before turning their attention to certolizumab (Cimzia), whose manufacturer is seeking a similar indication.
Belgium's UCB wants to market certolizumab for active axial spondyloarthritis, including AS patients. Certolizumab was initially approved to treat Crohn's disease in April 2008 and then rheumatoid arthritis in 2009.
In a randomized, controlled trial of more than 300 patients, 58% of patients taking 200 mg of certolizumab showed improvement, compared with 38% of those taking placebo (P=0.004), . For those taking 400 mg of certolizumab, 64% showed improvement (P<0.001).
Unlike with adalimumab, results do not appear to be driven by any given subgroup, the FDA said. The manufacturer enrolled enough patients with AS and nonradiographic axial spondyloarthritis to allow for a subgroup analysis.
"The treatment difference in the proportion of responders in the certolizumab treatment arms versus the placebo arm approximates 20% in most subgroups, irrespective of subgroup or x-ray reader, and is consistent with the overall trial population," FDA reviewers said.
The safety profile of certolizumab was similar to the already known profile of the drug, they added.