By*Nancy Walsh, Staff Writer, MedPage Today
Published: August 29, 2012

An FDA advisory panel has voted in favor of extending the use of
adalimumab (Humira) to ulcerative colitis, which would give patients an
additional biologic option for treatment -- one they could inject
themselves.

The agency had previously rejected the application by Abbott
Laboratories for this additional indication for the tumor necrosis
factor (TNF) inhibitor, arguing that studies had not conclusively
demonstrated efficacy.
But on Wednesday the Gastrointestinal Advisory Committee voted 12-2 that
the benefits of adalimumab outweighed the risks based on currently
available data. A final decision from the FDA is expected by the end of
the year.
The agency usually follows the recommendations of its advisory panels,
although it is not required to do so.
In the briefing documents prepared in advance of the committee meeting,
FDA staff reviewers had questioned whether a difference in rates of
clinical remission of less than 10% compared with placebo could be
considered "clinically meaningful."

The committee voted 15-2, with one abstention, that the observed
treatment differences in clinical remission at week 8 did represent a
clinically meaningful benefit.

In two randomized trials comparing adalimumab with placebo in patients
with moderate to severe ulcerative colitis, these rates of remission
were seen:

Study 826, week 8, 18.5% versus 9.2%, difference 9.3% (95% CI 0.8% to
17.9%, P=0.031)

Study 827, week 8, 16.5% versus 9.3%, difference 7.2% (95% CI 1.3 to
13.2, P=0.019)

Study 827, weeks 8 and 52, 8.5% versus 4.1%, difference 4.4% (95% CI 0.1
to 9, P=0.047)

The panel also determined that the observed treatment difference in the
number of patients with clinical remission at both weeks 8 and 52 was
clinically meaningful, with 10 voting Yes, six voting No, and one member
abstaining.

In the briefing documents, agency staff reviewers also questioned
whether the proposed 160-mg induction dose used for induction is
adequate. Pharmacologic studies suggested that greater remission rates
might be achieved with higher doses.

The committee voted 14-3 that the optimal dose for moderately to
severely active disease had not been adequately established.

Agency staff also suggested that an additional useful study might
explore the possibility that this treatment could have specific benefits
in certain subgroups of patients.

Adalimumab was approved for use in rheumatoid arthritis in 2002, and
approval has since been extended to several other conditions, including
psoriatic arthritis and Crohn's disease.

Conventional therapies for ulcerative colitis include immunosuppressive
agents and corticosteroids; one other TNF inhibitor, infliximab
(Remicade), also has been given approval as being safe and effective in
inflammatory bowel disease.

If approved, adalimumab could offer an alternative to infliximab,
particularly for patients who lose their response or are unable to
tolerate infliximab.

In addition, patients might prefer adalimumab, which can be
self-administered subcutaneously, rather than by infusion.

With regard to safety, the current labeling for the drug appears to be
adequate, including a boxed warning for malignancies and serious
infections, the FDA reviewers noted. Nor, they wrote, are there any new
safety concerns.

"The central review issue is whether the applicant has adequately
demonstrated and provided evidence of benefit sufficient to conclude
that the benefit outweighs the risks of Humira for this indication," the
staff review had stated, and concluded that it did so.

..
..
Donna G.
..

1) Rejoice always, Pray continually, Give thanks in all circumstances,
For this is God's will for you in Christ Jesus. ( I Thessalonians
5:16-18 NIV )

2) ANGELS EXIST, but some times, since they don't all have wings, we
call them FRIENDS......

3) Just because you're in pain, doesn't mean you have to be one!