For people with ankylosing spondylitis (AS) – a type of inflammatory arthritis that primarily affects the pelvis and spine – a pair of recent studies is shedding light on the possible benefits of a combination treatment with a nonsteroidal anti-inflammatory drug (NSAID) and a tumor necrosis factor (TNF) inhibitor (a type of biologic drug).
In AS, chronic inflammation in the sacroiliac joints (in the pelvis) and in the joints and ligaments along the spine creates pain and stiffness. During the early stages of the disease, joint damage may not be apparent in X-rays. (In these cases, the condition is called nonradiographic axial spondyloarthritis (nr-axSpA). As the disease progresses – and not all cases progress from nr-axSpA to AS – more joint damage occurs as the body grows new bone in an attempt to heal itself, which results in vertebrae fusing together. This reduces mobility and flexibility, and can lead to a hunched posture.
People with AS (as well as nr-axSpA) are typically first treated with an NSAID. If NSAID therapy isn’t enough, they may be treated with a TNF inhibitor, a type of biologic that blocks tumor necrosis factor, a cytokine (or molecule) that is involved in inflammation. But there is some controversy regarding treatment because study results have been inconsistent about whether TNF inhibitors or NSAIDs help stop progression of the disease or just control its symptoms.
Study data presented recently at the 2016 European Congress of Rheumatology may help settle the controversy. The two studies show that AS patients treated over a period of years with an NSAID and a TNF inhibitor, individually or together, have a lower risk of disease progression and a lower risk of developing new bone formation than those who did not take either a TNF inhibitor or an NSAID. And those who took both seemed to have the lowest risk of new bone development of all.
Lianne Gensler, MD, rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco Medical Center, and her colleagues presented two different studies based on data taken from the same group of AS patients, who were followed for at least two years.
The first analysis focused on how TNF inhibitors and NSAIDs separately affected “radiographic progression,” a common method that uses X-rays to measure how far the arthritis has progressed.
“We showed that TNF inhibitor use was associated with less progression over time. And in that model, NSAIDs were also associated independently with less progression,” says Dr. Gensler. Patients who had been on TNF inhibitors for 2 to 3½ years had the lowest risk of progression of all.
In the second study, Dr. Gensler’s group switched its focus to new bone formation, one of the main drivers of radiographic progression. In this analysis, they saw an interaction between the use of a TNF inhibitor and an NSAID. “There was a relationship between the NSAIDs and the TNF inhibitors,” says Dr. Gensler. “It’s the people taking NSAIDs and TNF inhibitors that have less new bone formation.”
Dr. Gensler notes that the length of time a patient was on these treatments and the amount of spinal damage they had prior to starting treatment were directly related to the amount of benefit they saw. “What we’re learning is that the earlier you start therapy and the longer you use it, the more likely you are to see the benefit of suppressing inflammation and therefore damage,” she says.
Joerg Ermann, MD, rheumatologist at Brigham and Women’s Hospital and instructor in medicine at Harvard Medical School, both in Boston, says that although the treatment controversy remains, shorter-term study results like these are vital to understanding this disease. “The structural damage of AS is a very slow process. The tools that we have available to measure new bone formation are not very sensitive to change. And it’s very difficult to run clinical trials [longer than] two years,” he says.
Digging deeper into these study results, Dr. Ermann adds that although it’s already been identified in a number of other studies, both of these studies provide further evidence that smoking is an important and preventable risk factor for progression and new bone formation in AS patients. In each study, patients who smoked had an approximately 2.5 greater chance of disease progression or seeing new bone formation than nonsmokers did. “There are many reasons not to smoke – cardiovascular disease, cancer, so forth – but smoking is specifically bad for patients with AS,” he says. “If [AS] patients smoke, they should definitely quit.”
Although these study results are encouraging for patients with AS, more research must be done before hard-and-fast conclusions can be drawn or changes to treatment guidelines for AS are considered. “You can’t look at this and say, you should definitely use both TNF inhibitors and NSAIDs in all patients to cause less radiographic progression,” says Dr. Gensler.
“Therapy should still be centered around quality of life and preserving function and symptom control – and less about trying to prevent [radiographic] damage, because you are only going to see that benefit in people that are at higher risk for progression,” she says.
Author: A. Kate MacDougall for the Arthritis Foundation