Remission in Axial Spondyloarthritis Unrelated to Gut Inflammation Save

Most patients with early, active axial spondyloarthritis (axSpA) who quickly received a tumor necrosis factor (TNF) inhibitor experienced remission, and it didn't matter whether or not they had intestinal inflammation at baseline, a small single-arm study found.

Sustained clinical remission while receiving golimumab (Simponi) was achieved by 61.8% of 58 patients in the trial, and the rate didn't differ significantly with respect to gut inflammation status (OR 1.50, 95% CI 0.39-6.49), according to Dirk Elewaut, MD, PhD, of Ghent University in Belgium, and colleagues.

But drug-free remission proved out of reach for most participants, the group reported in Arthritis & Rheumatology. As part of the protocol, patients achieving sustained remission then stopped all medications. Within 1 year, active axSpA recurred in 78.1%.

While the "remarkably high" initial response rate to first-line golimumab was heartening, the results didn't support the researchers' main hypothesis going into the study, which (according to its listing on Clinicaltrials.gov) was that "subclinical gut inflammation is an important predictor in therapy response and outcome."

This idea arose from earlier studies indicating that intestinal "dysbiosis" was common, but not universal, in axSpA, and that patients with gut inflammation tended to show worse SpA symptoms and were more likely to relapse quickly when biologic therapy was withdrawn. However, those studies were mostly conducted in patients with established axSpA. Elewaut and colleagues were interested in exploring these relationships in patients with recent disease onset, when irreversible structural damage hasn't yet set in.

Originally the researchers hoped to enroll nearly 150 patients, but recruitment proved more difficult than expected, largely because of the requirement that participants have symptom duration of less than 1 year. "Many of the newly diagnosed patients, referred to the participating study centres, had been experiencing disease symptoms for over a year," the researchers wrote.

Diagnostic delay is "a worldwide problem," they added, owing to the fact that back pain is the primary symptom and it often takes many months to rule out other potential causes. "In contrast to arthritic diseases primarily affecting the peripheral joints, where swelling and functional impairment are readily identifiable, axSpA patients struggle to specify the onset of their symptoms and often delay seeking professional healthcare," Elewaut and colleagues explained.

In the end, the researchers had to settle for 58 participants. Besides the 1-year limit on symptom duration, eligibility criteria included an age of 18-46, no treatment as of yet, and an Ankylosing Spondylitis Disease Activity Score as modified by C-reactive protein level (ASDAS-CRP) ≥2.1, indicating active disease.

Patients were first treated with full doses of a non-steroidal anti-inflammatory drug (NSAID) for 2 weeks; a second was then tried in patients whose ASDAS-CRP score did not fall below 1.3 or decline by at least 1.1 points to less than 2.1. At week 4, patients with ASDAS-CRP scores still above 1.3 were started on golimumab at 50 mg every 4 weeks.

The primary outcome was ASDAS-CRP score <1.3 at two consecutive visits conducted 12 weeks apart. Once a patient met this definition of sustained remission, NSAIDs and golimumab were withdrawn, with follow-up to week 52. Relapse was defined as an ASDAS-CRP score >1.3 plus an increase of at least 0.6 points from the level seen while in remission. A host of other axSpA symptom evaluations were performed as well.

Participants also underwent ileocolonoscopy at baseline to assess microscopic intestinal inflammation, with presence or absence determined by histopathologists blinded to patients' other information. A second biopsy was taken if and when patients achieved sustained remission; mucosal healing was a secondary study endpoint.

Mean patient age was 28, and just under 60% were men. ASDAS-CRP scores at baseline averaged 3.0. Microscopic gut inflammation was found in 28.6% of patients with evaluable biopsies.

In contrast to the initial hypothesis, rates of gut inflammation were somewhat higher in the group with sustained remission versus those without (28.6% vs 21.1%, P=0.6). Baseline factors that were associated with persistent disease activity included female sex, more severe axSpA symptoms, and a history of smoking.

Some 73% of patients went on golimumab after NSAID treatment failed to bring on remission. And the TNF inhibitor did seem to help patients obtain drug-free remission. After 200 days, just one patient who had stayed on NSAIDs was in drug-free remission, versus half of those who had taken golimumab.

Still, by week 52, only about 28% of the golimumab users were in drug-free remission.

The recruitment problem and other issues meant that only a few patients with gut inflammation at baseline had the post-remission biopsies. Mucosal healing was seen in all that did, but their small numbers made it impossible to try to correlate this outcome with ASDAS scores or other axSpA evaluations.

Elewaut and colleagues chalked up the study as a cautious win for early biologic therapy in newly diagnosed axSpA, but the role of intestinal inflammation remains uncertain in this population.