FDA Approves First Drug for Newly Defined Spinal Condition

The U.S. Food and Drug Administration (FDA) in late March approved the biologic medication certolizumab pegol (Cimzia), a tumor necrosis factor (TNF) inhibitor, to treat a newly defined condition called non-radiographic axial spondyloarthritis (nr-axSpA).

This spinal condition is now understood to be the early stage of ankylosing spondylitis (AS). Like AS, it causes chronic, disabling back pain, stiffness and fatigue. However, nr-axSpA lacks the hallmark feature of AS: X-ray evidence of structural damage to the sacroiliac joints, which connect the lower spine to the pelvis. (The descriptor “non-radiographic” comes from this lack of X-ray evidence.) This distinction has kept some people with nr-axSpA from getting effective treatment and symptom relief.

“By approving the first treatment for nr-axSpA, the FDA has finally agreed on the very existence of this condition, and they have also agreed that this condition is not ‘self-limiting’ [won’t get better on its own],” says rheumatologist Atul Deodhar, MD, professor of medicine at Oregon Health & Science University in Portland and lead author of the pivotal study leading to certolizumab pegol’s approval.

Earlier Identification and Treatment
The condition’s high burden of symptoms means early diagnosis followed by appropriate treatment can spare people with nr-axSpA years of pain, uncertainty and potentially accumulating damage to the spine.

The Centers for Disease Control and Prevention estimates that at least 2.7 million adults in the United States have axial spondyloarthritis (axSpA). Data suggest that among those, about half have nr-axSpA and half have AS. An estimated 5% to 12% of people with nr-axSpA develop AS two to five years after symptoms begin, though some never progress beyond this early stage of disease. For some patients, says Dr. Deodhar, the journey from the start of symptoms to diagnosis can take nearly a decade.

“This FDA approval gives more recognition to the early form of the disease and will help to reduce the delay in diagnosis and treatment,” says Steven Zhao, a rheumatologist in the United Kingdom, where four biologics are approved for nr-axSpA. “We know that damage to the spine takes time to develop: First there is inflammation in the spine that can be seen on MRI scans but not X-ray images, which we call nr-axSpA. Over time these bones fuse or become damaged to an extent that it can be seen on plain X-ray images, i.e., ankylosing spondylitis.”

Dr. Zhao, a clinical research assistant in the Department of Musculoskeletal Biology at the University of Liverpool, points out that interpreting X-ray films is not an exact science and that experts disagree on what level of damage is sufficient for a diagnosis of AS. “An approved treatment for nr-axSpA means patients will no longer be affected by this often unclear distinction between AS and nr-axSpA,” he says.

Trial Shows Biologic Effective
In the yearlong pivotal trial that led to certolizumab pegol’s approval for this condition, 317 adults with painful spinal symptoms and measurable signs of inflammation — including abnormally high C-reactive protein (CRP) and inflammation of the sacroiliac joints detected by magnetic resonance imaging (MRI) – were randomized to receive certolizumab pegol or a placebo.

Those in the placebo group continued various medications commonly used to treat nr-axSpA, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs (DMARDs). Patients in the placebo group whose disease activity remained high could switch to the biologic at any point during the trial.

By the end of the year, 47% of patients treated with certolizumab pegol had major improvements in disease activity (as measured by pain, stiffness, CRP level and other symptoms), compared with 7% of patients in the placebo group. Patients taking certolizumab pegol improved quickly, with 48% achieving a 40% improvement in pain, function and CRP levels after three months compared with 11% of placebo-treated patients.

The trial didn’t address whether certolizumab pegol could prevent nr-axSpA from progressing to full-blown AS, and it’s not yet known if this biologic or another treatment can stop the advance of the disease. It did, however, confirm that nr-axSpA won’t get better either on its own or with non-biologic treatments.

“The approval will be transformative for many patients living with this disease,” Dr. Deodhar predicts.

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