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Patients with axial spondyloarthritis may benefit from treatment with adalimumab (Humira) even if they don't have radiographic changes to the sacroiliac joints, researchers reported.

Among a cohort of patients with inflammation of the spine and sacroiliac joints visible only on MRI, significantly more of those receiving adalimumab for 12 weeks had a 40% improvement compared with those receiving placebo (36% versus 15%, P<0.001), according to Joachim Sieper, MD, of Charité University in Berlin, and colleagues.

Furthermore, 24% of the adalimumab group were considered to have inactive disease or clinical remission after 3 months, compared with only 4% of the placebo group (P<0.001), the researchers reported online in Annals of the Rheumatic Diseases.

Axial spondlyoarthritis as defined today includes both ankylosing spondylitis, a condition where sacroiliitis can be seen on x-rays, and "nonradiographic" axial spondyloarthritis, where inflammatory changes can be seen only on MRI.

The first-line treatment for both types of spinal disease is with nonsteroidal anti-inflammatory drugs (NSAIDs), and while tumor necrosis factor (TNF) inhibitors are approved for use in ankylosing spondylitis, there currently are no approved, effective second-line options for patients with the nonradiographic type.

To assess the suitability of anti-TNF therapy in this population, Sieper and colleagues enrolled 185 patients from multiple centers in Europe and North America who had active disease and an inadequate response to NSAID therapy.

Patients were randomized to receive 40 mg of adalimumab or placebo subcutaneously every other week for 3 months.

The primary endpoint was a 40% improvement on the criteria established by the Assessment of Spondyloarthritis International Society (ASAS40), which reflects patient evaluation of disease activity, pain, function, and inflammation or morning stiffness.

Patients' mean age was 38, and mean symptom duration was 10 years. Slightly more than half were women.

Certain patients were more likely to have an ASAS40 response:

• Symptom duration less than 5 years: 48% versus 6% (P=0.02)
• Age younger than 40: 46% versus 13% (P=0.05)
• High C-reactive protein levels at baseline: 55% versus 11% (P=0.03)

Significantly greater proportions of patients also showed greater changes from baseline on various other indices of disease activity and patient response compared with placebo:

• Bath Ankylosing Spondylitis Disease Activity Index: −1.9 versus −1 (P=0.004)
• Ankylosing Spondylitis Disease Activity Score: −1 versus −0.3 (P<0.001)
• Patient global assessment: −2.2 versus −0.9 (P<0.001)
• Total back pain: −2.3 versus −1.1 (P<0.001)

The most commonly reported adverse events associated with adalimumab were nasopharyngitis (11.6% of patients), nausea (7.4%), and headache (6.3%).

In the placebo group, 8.2% reported experiencing nausea, 7.2% had diarrhea, and 4.1% had upper respiratory tract infections.

Three patients in the adalimumab group had serious adverse events, including one case of acute hepatitis in a patient on isoniazid. No serious infections, malignancies, or opportunistic infections were seen.

"Results of this study provide important insights into the characteristics of patients with [nonradiographic axial spondyloarthritis] and the potential benefits of adalimumab therapy," Sieper and colleagues wrote.

One of these insights, according to the investigators, was that patients without visible sacroiliac x-ray involvement had disease activity levels comparable to what has been seen in clinical trials of anti-TNF therapy in patients with ankylosing spondylitis.

Other important findings were that "significant clinical improvement" was seen after only 12 weeks of treatment with adalimumab, and that responders were more likely to be younger, have shorter disease duration, and high levels of the inflammatory marker C-reactive protein.

Another major concern was that, on average, patients had been symptomatic for 7 years before being diagnosed, "which highlights the need for better ways to identify these patients," the investigators observed.

Limitations of the study were its short duration and inadequate power for full subgroup analyses.

Additionally, it was not designed to determine whether the treatment intervention could prevent nonradiographic disease from progressing to radiographic changes.

"Efficacy and safety results from this study suggest that adalimumab is an appropriate treatment option for active [nonradiographic axial spondyloarthritis] patients who fail NSAIDs, especially those with objective evidence of inflammation," the investigators concluded.

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