The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Humira (adalimumab) is a recombinant human IgG1 monoclonal
antibody indicated for reducing signs and symptoms and inhibiting
the progression of structural damage in adult patients with
moderately to severely active rheumatoid arthritis who have had an
inadequate response to one or more DMARDs. Humira is supplied in
single-use, 1 mL pre-filled glass syringes, and also 2 mL glass
vials as a sterile, preservative-free solution for subcutaneous
The recommended dose of Humira for adult patients with
rheumatoid arthritis is 40 mg administered every other week as a
The FDA approved Humira on December 31, 2002, nine months after
simultaneous regulatory submissions in the United States and
The efficacy and safety of Humira were assessed in four
randomized, double blind studies in Subjects with active rheumatoid
arthritis. Humira was administered subcutaneously in combination
with MTX or as monotherapy or with other disease modifying
Study I evaluated 271 subjects whom had failed therapy with at
least one but no more than four DMARDs and had inadequate response
to MTX. Doses of 20, 40 or 80 mg of Humira or placebo were given
every other week for 24 weeks.
Study II evaluated 544 Subjects who had failed therapy with at
least one DMARD. Doses of placebo, 20 or 40 mg of Humira were given
as monotherapy every other week or weekly for 26 weeks.
Study III evaluated 619 Subjects who had an inadequate response
to MTX. Subjects received placebo, 40 mg of Humira every other week
with placebo injections on alternate weeks, or 20 mg of Humira
weekly for up to 52 weeks. Study III had an additional primary
endpoint at 52 weeks of inhibition of disease progression.
Study IV assessed safety in 636 Subjects who were either
DMARD-naive or were permitted to remain on their pre-existing
rheumatologic therapy provided that therapy was stable for a
minimum of 28 days. Subjects were randomized to 40 mg of Humira or
placebo every other week for 24 weeks.
In all four studies, Humira showed significantly greater
improvement than placebo in the disability index of Health
Assessment Questionnaire from baseline to the end of study, and
significantly greater improvement than placebo in the
health-outcomes as assessed by The Short Form Health Survey.
Improvement was seen in both the Physical Component Summary and the
Mental Component Summary.
Adverse events associated with the use of Humira may include
(but are not limited to) the following:
- Upper respiratory infection
- Flu syndrome
- Abdominal pain
Mechanism of Action
Adalimumab binds specifically to TNF-alpha and blocks its
interaction with the p55 and p75 cell surface TNF receptors.
Adalimumab also lyses surface TNF expressing cells in vitro in the
presence of complement. Adalimumab does not bind or inactivate
lymphotoxin (TNF-beta). TNF is a naturally occurring cytokine that
is involved in normal inflammatory and immune responses. Elevated
levels of TNF are found in the synovial fluid of rheumatoid
arthritis patients and play an important role in both the
pathologic inflammation and the joint destruction that are
hallmarks of rheumatoid arthritis.
Adalimumab also modulates biological responses that are induced
or regulated by TNF, including changes in the levels of adhesion
molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and
ICAM-1 with an IC50 of 1-2 X 10-10M).
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