Anti-TNF Therapy Slows Down AS Progression and Bone Loss, Study Says
Anti-TNF therapies can halt disease progression and bone loss, and are associated with clinical improvement in people with ankylosing spondylitis after one year of treatment, a study shows.
The study, “Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis,” was published in the journal Clinical Rheumatology.
People with ankylosing spondylitis (AS), a type of arthritis that affects the joints of the spine, have an increased risk of bone fracture which is caused by low bone mineral density (BMD). A decrease in BMD arises from an inflammatory-induced imbalance between bone formation and bone break-down (resorption). When bone resorption is higher than bone formation, bones lose density and weaken.
The increased risk of bone fracture caused by this imbalance is also seen in other inflammatory conditions such as rheumatoid arthritis (RA), a disease that affects joints and other organs.
Given this imbalance is in part triggered by the signaling protein tumor necrosis factor-alpha (TNF-α) — a master regulator of inflammation — anti-TNF therapies have been used to treat both AS and RA.
Despite the improvements in AS and RA disease activity following anti-TNF therapy, some uncertainty remains as to the specific mechanism of these therapies.
Therefore, researchers conducted a study to assess bone density and bone markers — parameters that reflect disease progression and/or success of treatment — after one year of anti-TNF therapy.
A total of 53 patients with active inflammatory arthritis — who had never been treated with anti-TNF therapies — were recruited for the study (17 with AS and 36 with RA). Of these patients, 34 were women and 19 were men, with an average disease duration of 8.5 years and an average age of 52 years.
AS patients and 20 RA patients were treated with 50 mg per week of Enbrel (etanercept), by Amgen, while 16 RA patients received Cimzia (certolizumab), by Union Chimique Belge (UCB), starting at 400 mg every two weeks for four weeks, followed by 200 mg twice weekly. Of the RA patients, 28 had been taking methotrexate prior to the study, and doses were not changed.
Overall disease progression was assessed before the study began, and after three, six, and 12 months of therapy. Bone density was evaluated before the study, and after one year of treatment. Bone markers were determined before the study and after three and six months of treatment.
In patients with AS, one year of anti-TNF therapy significantly decreased Bath Ankylosing Spondylitis Disease Activity Indexes (BASDAI) scores — a measure of AS disease severity on a scale from zero to 10. The higher the score, the more severe the disease.
Before the study, the average BASDAI score was 5.79. The score reduced to 2.04 after three months of therapy, and to 1.86 after one year.
In addition, the therapy caused a significant decrease in serum C reactive protein (CRP), which is a marker of inflammation. CRP decreased from 12.5 before the study, to 5.7 after three months and then 4.4 after one year of therapy.
Anti-TNF therapy in RA patients was also effective at significantly reducing disease severity and CRP levels.
The therapy stopped overall bone loss in both AS and RA patients, with no significant changes in BMD in patients’ vertebrae and femoral neck (the area located in the upper portion of the femur) after one year.
In AS, levels of procollagen type I N-propeptide (P1NP) — a marker for bone formation — significantly increased, rising from 49.2 before the study to 56.9 after one year of treatment. P1NP levels also increased in RA patients.
Bone markers associated with bone resorption (bone loss) were significantly reduced in both AS and RA patients.
A final statistical analysis of the data revealed that the most significant predictor of BMD in AS patients were the blood levels of CRP.
“Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction,” the researchers stated.