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Among patients with axial spondyloarthritis who achieved remission during treatment with ixekizumab (Taltz), those who continued on treatment were less likely to flare than were those who withdrew from treatment, a randomized trial found.

At week 40 following randomized treatment continuation or withdrawal, 83.3% of patients who remained on ixekizumab were flare-free compared with 54.7% of those who had switched to placebo (P<0.001), reported Robert Landewé, MD, PhD, of the Amsterdam Rheumatology and Immunology Center in the Netherlands, and colleagues.

The overall 83.3% of patients who remained flare-free at week 40 with treatment continuation was also observed in those who were receiving ixekizumab in doses of 80 mg every 2 weeks or 80 mg every 4 weeks, both of which were significantly greater than with placebo (P=0.001 and P=0.003), they noted online in .

There is considerable interest in the possibility of withdrawing treatment or lowering doses of biologic therapies for inflammatory and rheumatic diseases, for reasons including potential adverse effects with long-term use and the high cost of medications.

Previous studies in which tumor necrosis factor (TNF) inhibitors were withdrawn found increased rates of flare, although in , reducing the dose frequency of certolizumab (Cimzia) was not associated with a greater likelihood of flare.

Ixekizumab is a monoclonal antibody that targets interleukin (IL)-17A and has been approved for both radiographic and nonradiographic axial spondyloarthritis. Whether treatment withdrawal after remission could be achieved with IL-17 inhibition had not previously been investigated.

To examine this, Landewé and colleagues reported on a 104-week long-term extension study known as COAST-Y that included a 24-week open-label phase and a 40-week double-blind randomized withdrawal-retreatment period. Patients who had achieved remission at week 24 with doses of 80 mg every 2 weeks or every 4 weeks were randomly assigned to either continue on their assigned dose or to placebo.

Remission was defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 1.3 or lower at week 16 or week 20 or 2.1 or less at both visits. Flare was defined as an ASDAS of 2.1 or higher at two consecutive study visits or above 3.5 at any time.

The study included 773 patients who had originally completed 52 weeks of treatment in two studies of ixekizumab for radiographic axial spondyloarthritis and one for nonradiographic disease. Participants' mean age was 43, more than two-thirds were men, and symptom duration was almost 16 years.

Nonsteroidal anti-inflammatory drugs had been used by 88% of participants, while 36% had used conventional disease-modifying antirheumatic drugs, and 20% had used TNF inhibitors.

At baseline, mean ASDAS was 2.3; at the time of withdrawal randomization, it was 1.3.

A total of 155 patients entered the randomized withdrawal phase of the trial. Among this group, mean age was 38 and mean duration of symptoms was 13 years. Two-thirds had radiographic disease.

Time to flare was significantly longer in patients who remained on treatment versus those who withdrew, with separation on the Kaplan-Meier treatment survival curves being first observed at week 20.

Factors that were identified in a post-hoc analysis as being associated with flare (other than withdrawal of ixekizumab) included body mass index outside of the normal range, the development of antidrug antibodies, higher baseline level of C-reactive protein, and larger ASDAS area under the curve.

Serious adverse events were reported in two patients in the every-4-week group, in two patients in the every-2-week group, and in one patient in the placebo group, with only one (Clostridium difficile colitis) leading to treatment discontinuation. Otherwise, there were no new safety signals.

At the time of flare, the mean ASDAS was 2.9 among patients on ixekizumab every 4 weeks, 2.8 for those on ixekizumab every 2 weeks, and 3.5 for patients who had been withdrawn to placebo.

Among patients on placebo who flared and then were re-treated with open-label ixekizumab, ASDAS low disease activity was regained by week 16 in 93% and inactive disease in 44%. This ability to regain disease control after flare is similar to what has been seen with TNF inhibitors. "Longer-term data from this ongoing study (with up to 80 weeks of randomized withdrawal) will likely provide additional information regarding response to retreatment with ixekizumab, as well as predictors of flare," the investigators wrote.

More than half of patients who were randomized to placebo had no flares for up to 40 weeks, and most were flare-free for 20 weeks. This "long durability of treatment response following withdrawal of ixekizumab suggests that temporary treatment interruption, such as during infection or prior to surgical procedures, is unlikely to result in flare for most patients," they noted.

A limitation of the study was that it did not consider tapering treatment, rather than withdrawal.

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