Diana G.

Nunez
Biology 1615
November 7, 2014

Summary of Efficacy and Safety of Adalimumab in Patients With Ankylosing

Spondylitis
Desiree van der Heijde, Alan Kivitz, Michael H. Schiff, Joachim Sieper, Ben A. C.
Dijkmans,Jurgen Braun, Maxime Dougados, John D. Reveille,Robert L. Wong, Hartmut
Kupper, and John C. Davis, Jr., for the ATLAS Study Group in their article Efficacy and Safety
of Adalimumab in Patients With Ankylosing Spondylitis from Arthritis and Reumatism wrote
about a study to show the effects of adalimumab-treatment in comparison with placebo in
patients with ankylosing spondylitis.
The study was conducted for 24 weeks, and the patients were injected with 40 mg of
adalimumab every other week. The results would be compared with patients whose treatment
was the placebo. There are two measures: the first one at week 12 and the second one at week
24. At week 12, there was a difference of about 30% for patients treated with adalimumab. In
both groups of patients, side effects were detected such as infections, but in this case the
difference was less significant, around 15%.
An advisory group selected specific patients: people who had ankylosing spondylitis
(AS). This is an inflammatory disease that affects the skeleton, produces pain, limits mobility
and could end in the spine being immobilized because AS can cause fusions in the vertebrae. A
higher incidence has been found of this disease in individuals with the following characteristics:
white people, men, and elderly.

Tumor necrosis factor (TNF) produces inflammation in patients with AS. In biopsies
taken from individuals with AS, high levels of TNA in the genetic information has been found.
There are a few treatments for this disease, which while offering relief to the symptoms, improve
spinal mobility. Placebo tests, using antibody or a receptor construct have shown a significant
improvement in TNF lock. Patients showed improvement in symptoms and mobility. In longterm studies, adalimumab has been shown to be safe, effective treatment applied to patients with
rehumatoid arthritis (AR) and psoriatic arthritis (PsA). The study was made by the scientific
group and Abbott Laboratories.
The population used was people greater than 18 years old with AS. People who had been
treated with specific anti-TNF medications or had received corticosteroids 4 weeks before the
study were remove. Patients were tested with skin tests for tuberculosis (TB) and a radiograph.
People with inactive TB were accepted in the study. Patients with infections who needed the use
of antibiotic and others specific diseases like hepatitis, cardiac, renal, or cancer were excluded.
The dosage applied in the study was 40 mg of adalimumab every two weeks. People who didnt
show 20% of progression at the weeks 12, 16, or 20 left the study, and the remaining patients
continued treatment over 80 weeks.
The study was done in different countries in Europe and in America. There were two
efficacy ends points to make the evaluation. The study was applied from January 27, 2004 and
December 23, 2004. The primary efficacy end point was at the week 12 measure patients.
ASAS20 refers patients to have a 20% improvement in at last 1 of 4 domains as pain, function,
functional index, and inflammation. Secondary efficacy end point refers to patients getting a
drug with 40% response (ASAS40) in 5 of 6 domains, the same for primary efficacy end point
plus spinal mobility and acute-phase reactants.

The BASMI is an index for measured anterior lumbar flexion, lumbar side flexion,
intermalleolar distance, tragus-to-wall distance, and cervical rotation. The measures are made in
scale 0-10, in degrees, and cm.
In the beginning of the study, 347 patients were screened and only 315 were randomly
assigned to treat. 208 patients were treated with adalimumab and 107 with placebo. At week 12,
103 patients completed the study with placebo and 204 patients with adalimumab. At week 24
101 patients continued with placebo treatment and 195 patients with adalimumab. Patients
withdrew from the study for different reasons like adverse events, lost to follow-up, or withdraw
consent. The results showed more efficient response in the patients with adalimumab than the
patients with placebo treatment.
The BASDAI is the measure of others symptoms: extreme fatigue, spinal and peripheral
joint pain, morning oppression sense, and chest expansion. Chest expansion is a test to compare
the chest circumference in a deep expiration and a deep inhalation.
In the weeks 4, 12, 16, and 24, laboratory evaluations were made to measure vital signs
and statistically registered to make comparisons between both groups.
At week 12, patients treated with adalimumab showed 58.2% of ASAS20, and 20.6%
improvement in patients treated with placebo. A small group of patients with total spinal
ankylosing were part of this study and 3 of 6 patients treated with andalimumab showed
improvement at week 12, and neither patient of 5 patients responded with placebo.
On BASDAI scores 45.2%of patient treated with adalimumab improved and only 15.9%
patients improved with placebo. At week 12 and 24, patients with adalimumab showed a
significant improvement in ASAS40 compared with the group treated with placebo.

HLA-B27-positive patients improved 62.0% in ASAS20 in comparison with 23.5%

improvement for patients treated with placebo. At week 24 adalimumab patients had a 75.0%
incidence of nonserius infections compared with 59.8% in patients treated with placebo. No
deaths occurred in the study, and no infections like tuberculosis. 6 of the 208 people that
received adalimumab presented serious events in comparison to 3 patient treated with placebo.
The results said that adalimumab improves the symptoms in 58.2% in patients with AS at week
12. Radiology evidence showed that adilumamub is associated with significant improvement in
patients and was well-tolerated.
In conclusion, this study with adalimumab showed significant improvement in the signs
and symptoms for patients with active AS. More studies are necessary to know the long-term
effect of adalimumab in patients with AS.