One-quarter of patients with axial SpA remain flare-free after ceasing etanercept
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In patients with non-radiographic axial spondyloarthritis who achieved inactive disease with etanercept, approximately 25% remained flare-free at 40 weeks after ceasing treatment, according to data published in the Journal of Rheumatology.
“Patients with [axial SpA (axSpA)] typically have disease onset early in life, and are likely to start [TNF inhibitor (TNFi)] treatment early; therefore, treatment withdrawal upon achieving inactive disease is especially relevant,” Filip Van den Bosch, MD, PhD, of the department of internal medicine and pediatrics at Ghent University, in Belgium, and colleagues wrote. “Data on outcomes following treatment cessation, as well as understanding which patients might best respond, would be highly informative to patients and physicians.”
To analyze the impact of treatment discontinuation in patients with non-radiographic axial SpA receiving etanercept (Enbrel, Amgen), Van den Bosch and colleagues conducted RE-EMBARK, a multicenter, open-label study from September 2015 through September 2019. The study comprised three periods. During the first, all enrolled patients received etanercept 50 mg once per week for 24 weeks. Patients were allowed one NSAID at a dose determined by the investigator they were working with.
Patients who achieved an Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) of less than 1.3 at week 24 entered period two. This period featured a 40-week withdrawal period during which patients only continued taking their NSAID. If patients experienced a disease flare before week 64, they entered period three, where they received etanercept 50 mg weekly.
Enrolled patients were those aged 18 to 49 years who had active, confirmed non-radiographic axial SpA. Those with radiographic disease were excluded. The primary outcome was the proportion of patients who demonstrated a disease flare following treatment discontinuation. Among the predefined secondary endpoints was the estimated time to flare following withdrawal. Other endpoints included 24-week etanercept efficacy and 12-week efficacy in patients who experienced a flare during period two.
Among the 209 patients who received open-label etanercept in part one, 119 achieved inactive disease and entered the withdrawal period. Data were missing for three patients in this group. Of those with completed data, 22.3% demonstrated a flare within 4 weeks of ceasing etanercept, and 67% experienced a flare at 40 weeks. In all, 74.8% of patients experienced a flare at some point during period two, according to the researchers.
Among the patients who entered period three after experiencing a flare during treatment withdrawal, 62.1% were able to regain inactive disease states. There were no unexpected safety results, the researchers wrote.
“Whereas most patients with [non-radiographic axial SpA (nr-axSpA)] who achieved inactive disease with [etanercept (ETN)] flared after ETN withdrawal, a quarter of the patients did not experience ASDAS flare for 40 weeks despite treatment discontinuation,” Van den Bosch and colleagues wrote. “While this is an encouraging outcome for early aggressive treatment with a TNFi in patients with nr-axSpA, further studies with longer follow-up are needed.”
Perspective
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Charles Pritchard, MD, FACP, FACR, RhMSUS
This study was requested by the European Medicines Agency to assess the frequency of flare in non-radiographic axial spondyloarthritis patients in remission on etanercept (Enbrel, Amgen) after etanercept withdrawal.
The 2016 Assessment of the Spondyloarthritis International Society (ASAS) has suggested tapering of biologic DMARDs in patients with inactive axial SpA. The 2019 American College of Rheumatology recommendations for non-radiographic axial SpA advise against tapering.
Several prior withdrawal studies with etanercept, other anti-TNF agents, and an anti-IL-17 agent have shown similar results, with a portion remaining in sustained remission and some patients flaring. These patients who experienced flare mostly re-achieved remission upon restarting the medication.
Clearly this study adds to the literature that a large proportion of those in remission will flare upon withdrawal of the biologic DMARD. This gives us a sense of the timing, for example regarding necessary temporary withdrawal for surgery or infections. It also gives us a sense of which patients might tolerate discontinuing a medication. What is not evaluated by this study is the effect of partial tapering of medications by our patients, which compliance studies would suggest is happening all the time without the knowledge of the prescriber.
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